The integration of advanced diagnostic and therapeutic capabilities in oncology has given rise to phototheranostics,a field that combines the precision of imaging with the selectivity of light-activated treatments.Due...The integration of advanced diagnostic and therapeutic capabilities in oncology has given rise to phototheranostics,a field that combines the precision of imaging with the selectivity of light-activated treatments.Due to their pronounced near-infrared(NIR)absorption,tunable molecular structures,and commendable stability,organic photovoltaic non-fullerene acceptors(NFAs)represent a promising frontier in cancer management.Despite the great potential of NFAs in phototheranostics,there is currently a lack of systematic reviews in this field.This review provides a meticulous examination of the current state of NFAs in the field of phototheranostics,highlighting the strategic approaches to spectral red-shifting that enhance tissue penetration and therapeutic efficacy.It dissects the link between molecular architecture and performance across key therapeutic and diagnostic modalities,including photothermal therapy(PTT),photodynamic therapy(PDT),and fluorescence imaging(FLI).In addition,the review presents a concise analysis of the challenges and milestones in the clinical translation of NFAs,offering insights into the innovations required to overcome existing barriers.展开更多
Recently emerging Type-I photodynamic therapy holds significant promise in addressing the hypoxia challenge encountered by traditional oxygen-dependent Type-II photosensitizers(PSs)in photodynamic oncotherapy.The key ...Recently emerging Type-I photodynamic therapy holds significant promise in addressing the hypoxia challenge encountered by traditional oxygen-dependent Type-II photosensitizers(PSs)in photodynamic oncotherapy.The key hurdle in engineering Type-I PSs lies in enhancing the electron transfer capabilities of these molecules,enabling them to efficiently convert H_(2)O or oxygen-based substrates into reactive oxygen species.Herein,we propose to construct intramolecular electric fields in the second near-infrared(NIR-II)emissive organic PSs to regulate the local electron density for boosting hypoxia-tolerant cancer phototheranostics.Upon introducing the molecular cationization approach and electron programming strategy,the resultant cationic semiconducting architecture achieves electron distribution rearrangement,forms intramolecular electric fields,and facilitates electron transfer path,resulting in a 50-fold amplification of electrostatic potential difference,thereby accelerating the hydroxyl radical(•OH)-dominant Type-I photosensitization process.In vitro studies disclose that the tailor-made nanomaterial selectively targets the mitochondria and causesmitochondria-mediated cancer cell apoptosis under laser irradiation.Notably,this as-prepared nanoplatform enables NIR-II fluorescence imaging-assisted phototherapy and exhibits in vivo antitumor efficacy on 4T1-bearing mouse models.We believe that this contribution will launch the future of NIR-II emitting Type-I PSs and enlighten scientific researchers to exploit high-efficiency phototheranostic agents for cancer therapy.展开更多
Phototheranostics that concurrently and complementarily integrate real-time diagnosis and in situ therapeutic capabilities in one platform has become the advancing edge of precision medicine.Organic agents possess the...Phototheranostics that concurrently and complementarily integrate real-time diagnosis and in situ therapeutic capabilities in one platform has become the advancing edge of precision medicine.Organic agents possess the merits of facile preparation,high purity,tunable photophysical property,good biocompatibility,and potential biodegradability,which have shown great promise for disease theranostics.This review summarizes the recent achievements of organic phototheranostic agents and applications,especially which rationally utilize energy dissipation pathways of Jablonski diagram to modulate the fluorescence emission,photoacoustic/photothermal production,and photodynamic processes.Of particular interest are the systems exhibiting huge differences in aggregate state as compared with the solution or single molecule form,during which the intramolecular motions play an important role in regulating the photophysical properties.The recent advances from such an aspect for biomedical applications including high-resolution imaging,activatable imaging and therapy,adaptive theranostics,image-guided surgery,immunotherapy,and afterglow imaging are discussed.A brief summary and perspective in this field are also presented.We hope this review will be helpful to the researchers interested in bioprobe design and theranostic applications,and inspire new insights into the linkage between aggregate science and biomedical field.展开更多
Exploration of single molecular species synchronously featured by long excitation/emission wavelength, accurate diagnosis, and effective therapy, remains supremely appealing to implement high-performance cancer photot...Exploration of single molecular species synchronously featured by long excitation/emission wavelength, accurate diagnosis, and effective therapy, remains supremely appealing to implement high-performance cancer phototheranostics. However, those previously established phototheranostic agents are undiversified and stereotyped in terms of structural skeleton, and generally exhibit insufficient phototheranostic outcomes. Herein, we innovatively utilized indanone-condensed thiadiazolo[3,4-g]quinoxaline(ITQ) as electron acceptor to construct novel photosensitizer with second near-infrared(NIR-II) emission. Experimental study and theoretical calculation demonstrated that comparing with the counterparts constituting by widely employed NIR-II building block benzobisthiadiazole(BBTD) and 6,7-diphenylthiadiazoloquinoxaline(DPTQ), ITQ-based photosensitizer(TITQ) showed superior aggregation-induced emission(AIE) characteristics, much stronger type-I reactive oxygen species(ROS) production, and prominent photothermal conversion capacity. Furthermore, TITQ nanoparticles with excellent biocompatibility were capable of effectively accumulating in the tumor site and visualizing tumor through fluorescence-photoacoustic-photothermal trimodal imaging with highly spatiotemporal resolution, and completely eliminating tumor by type-I photodynamic-photothermal therapy.展开更多
Phototheranostics integrates deep-tissue imaging with phototherapy(containing photothermal therapy and photodynamic therapy),holding great promise in early diagnosis and precision treatment of cancers.Recently,second ...Phototheranostics integrates deep-tissue imaging with phototherapy(containing photothermal therapy and photodynamic therapy),holding great promise in early diagnosis and precision treatment of cancers.Recently,second near-infrared(NIR-II)fluorescence imaging exhibits the merits of high accuracy and specificity,as well as real-time detection.Among the NIR-II fluorophores,organic small molecular fluorophores have shown superior properties in the biocompatibility,variable structure,and tunable emission wavelength than the inorganic NIR-II materials.What’s more,some small molecular fluorophores also display excellent cytotoxicity when illuminated with the NIR laser.This review summarizes the progress of small molecular NIR-II fluorophores with different central cores for cancer phototheranostics in the past few years,focusing on the molecular structures and phototheranostic performances.Furthermore,challenges and prospects of future development toward clinical translation are discussed.展开更多
Broadband photothermal and photoacoustic agents in the near-infrared(NIR)biowindow are of significance for cancer phototheranostics.In this work,Pt Cu nanosheets with an average lateral size of less than 10 nm are syn...Broadband photothermal and photoacoustic agents in the near-infrared(NIR)biowindow are of significance for cancer phototheranostics.In this work,Pt Cu nanosheets with an average lateral size of less than 10 nm are synthesized as NIR photothermal and photoacoustic agents in vivo,which show strong light absorption from NIR-I to NIR-II biowindows with the photothermal conversion efficiencies of 20.4%under 808 nm laser and 32.7%under 1064 nm laser.Pt Cu nanosheets functionalized with folic acidmodified thiol-poly(ethylene glycol)(SH-PEG-FA)present good biocompatibility and 4T1 tumor-targeted effect,which give high-contrast photoacoustic imaging and efficient photothermal ablation of 4T1 tumor in both NIR-I and NIR-II biowindows.Our work significantly broadens applications of noble metal-based nanomaterials in the fields of cancer phototheranostics by rationally designing their structures and modulating their physicochemical properties.展开更多
Phototheranostics have attracted tremendous attention in cancer diagnosis and treatment because of the noninvasiveness and promising effectiveness.Developing advanced phototheranostic agents with long emission wavelen...Phototheranostics have attracted tremendous attention in cancer diagnosis and treatment because of the noninvasiveness and promising effectiveness.Developing advanced phototheranostic agents with long emission wavelength,excellent biocompatibility,great tumor-targeting capability,and efficient therapeutic effect is highly desirable.However,the mutual constraint between imaging and therapeutic functions usually hinders their wide applications in biomedical field.To balance this contradiction,we herein rationally designed and synthesized three novel tumor-targeted NIR-Ⅱ probes(QR-2PEG_(321),QR-2PEG_(1000),and QR-2PEG_(5000)) by conjugating three different chain lengths of PEG onto an integrin α_(v)β_(3)-targeted NIR-Ⅱ heptamethine cyanine fluorophore,respectively.In virtue of the essential amphiphilic characteristics of PEG polymers,these probes display various degree of aggregation in aqueous buffer accompanying with differential NIR-Ⅱ imaging and photothermal(PTT) therapeutic performance.Both in vitro and in vivo results have demonstrated that probe QR-2PEG_(5000) has the best NIR-Ⅱ imaging performance with prominent renal clearance,whereas QR-2PEG_(321)possesses excellent photoacoustic signal as well as PTT effect,which undoubtedly provides a promising toolbox for tumor diagnosis and therapy.We thus envision that these synthesized probes have great potential to be explored as a toolkit for precise diagnosis and treatment of malignant tumors.展开更多
The small molecular second near-infrared(NIR-Ⅱ, 1000–1700 nm) dye-based nanotheranostics can concurrently combine deep-tissue photodiagnosis with in situ phototherapy, which occupies a vital position in the early de...The small molecular second near-infrared(NIR-Ⅱ, 1000–1700 nm) dye-based nanotheranostics can concurrently combine deep-tissue photodiagnosis with in situ phototherapy, which occupies a vital position in the early detection and precise treatment of tumors. However, the development of small molecular NIR-Ⅱ dyes is still challenging due to the limited electron acceptors and cumbersome synthetic routes.Herein, we report a novel molecular electron acceptor, boron difluoride formazanate(BDF). Based on BDF, a new small molecular NIR-Ⅱ dye BDF1005 is designed and synthesized with strong NIR-I absorption at 768 nm and bright NIR-Ⅱ peak emission at 1034 nm. In vitro and in vivo experiments demonstrate that BDF1005-based nanotheranostics can be applied for NIR-Ⅱ fluorescence imaging-guided photothermal therapy of 4T1 tumor-bearing mice. Under 808 nm laser irradiation, tumor growth can be effectively inhibited. This work opens up a new road for the exploitation of NIR-Ⅱ small molecular dyes for cancer phototheranostics.展开更多
Phototheranostic with highly integrated functions is an attractive platform for cancer management. It remains challenging to develop a facile phototheranostic platform with complementary bimodal imaging and combinatio...Phototheranostic with highly integrated functions is an attractive platform for cancer management. It remains challenging to develop a facile phototheranostic platform with complementary bimodal imaging and combinational therapy capacity. Herein, the small-molecule cyanine IR780 loaded liposomes have been harnessed as a nanoplatform to simultaneously realize photoacoustic(PA)/the second near-infrared window(NIR-Ⅱ) fluorescence imaging and image-guided surgery/adjuvant photothermal therapy(PTT).This nanoplatform exhibits attractive properties like uniform controllable size, stable dispersibility, NIR-Ⅱ fluorescence emission, photothermal conversion, and biocompatibility. Benefiting from the complementary PA/NIR-Ⅱ fluorescence bimodal imaging, this nanoplatform was successfully applied in precise vasculature delineation and tumor diagnosis. Interestingly, the tumor was clearly detected by NIR-Ⅱ fluorescence imaging with the highest tumor-to-normal-tissue ratio up to 12.69, while signal interference from the liver was significantly reduced, due to the difference in the elimination rate of the nanoplatform in the liver and tumor. Under the precise guidance of the image, the tumor was accurately resected, and the simulated residual lesion after surgery was completely ablated by adjuvant PTT. This combined therapy showed improved antitumor efcacy over the individual surgery or PTT. This work develops a facile phototheranostic nanoplatform with great significance in accurately diagnosing and effectively treating tumors using simple NIR light irradiation.展开更多
Human papillomavirus(HPV)is a highly prevalent venereal pathogen accounting for genital warts and various cancers like cervical,anal,and oropharyngeal cancers.Although imiquimod,a topical medication,is commonly used t...Human papillomavirus(HPV)is a highly prevalent venereal pathogen accounting for genital warts and various cancers like cervical,anal,and oropharyngeal cancers.Although imiquimod,a topical medication,is commonly used to treat genital warts induced by HPV,its potential as an in situ immune response regulator for HPV-related cancers has rarely been explored.In this study,we developed an innovative synergistic therapeutic platform by integrating near-infrared-II(NIR-II)absorbing aggregationinduced emission(AIE)agent(TPE-BT-BBTD)and imiquimod into an injectable hydrogel named TIH.TPE-BT-BBTD molecule that serves as a photothermal agent,with exposure to a 1064 nm laser,effectively destroys tumor cells and releases tumor-related antigens.During the thermogenesis process,the hydrogel melts and releases imiquimod.The released imiquimod,in conjunction with the dead tumor antigens,stimulates dendritic cellmaturation,activating the immune system to ultimately eliminate residual cancer cells.This novel approach combines the immunomodulatory effects of imiquimod with a 1064 nm-excitable photothermal agent in a hydrogel delivery system,offering a promising tactic for combating HPV-associated cancers.展开更多
Tuberculosis(TB)infection,caused by Mycobacterium tuberculo-sis,reveals tens of millions of new cases and causes millions of deaths each year.The traditional clinical treatment for TB is long-term and combined usage o...Tuberculosis(TB)infection,caused by Mycobacterium tuberculo-sis,reveals tens of millions of new cases and causes millions of deaths each year.The traditional clinical treatment for TB is long-term and combined usage of antibiotics but suffers from poor lesion and pathogen targeting,insufficient efficacy,high systemic toxicity,and ineffectiveness against drug-resistant M.tuberculosis.As a characteristic lesion of TB,granulomas have a compact construction,which greatly limits the access of small-molecule antibiotics to the necrotic area to kill M.tuberculosis[1].展开更多
Aggregation-induced emission luminogens(AIEgens)have been prosperously developed and applied in the fields of optical imaging and theranostics since its establishment.Nowadays,AIEgens can fulfill nearly all requiremen...Aggregation-induced emission luminogens(AIEgens)have been prosperously developed and applied in the fields of optical imaging and theranostics since its establishment.Nowadays,AIEgens can fulfill nearly all requirements in optical imaging and theranostics with emission spectra ranging from visible to near-infrared wavelengths.Although a variety of AIEgens with varying wavelengths and functionalities have been continuously designed,their performance is heavily dependent on the use of conventional light sources,such as xenon lamps and lasers,which severely hinder further applications due to limited penetration depth and background autofluorescence in biological tissues.To mitigate these limitations and maximize the potential of AIEgens,unconventional excitation sources such as chemical energy,ultrasound,and X-ray offer effective alternatives that circumvent the drawbacks associated with traditional light-based constant excitation.In this Review,we introduce the fundamental principles governing the combination of unconventional excitation sources with AIEgens,highlight recent advancements in using AIEgens excited by these unconventional sources for bioimaging and theranostics,and discuss current challenges and future perspectives aimed at advancing the biomedical applications of AIEgens.展开更多
Cancer immunotherapy is a groundbreaking treatment that utilizes the body’s immune system to fight against cancers.Despite the clinical application of several immunotherapeutic agents,challenges persist,including lim...Cancer immunotherapy is a groundbreaking treatment that utilizes the body’s immune system to fight against cancers.Despite the clinical application of several immunotherapeutic agents,challenges persist,including limited patient responsiveness and adverse events stemming from immune activation,which constrain overall efficacy.Recent advances in aggregation-induced emission luminogens(AIEgens)have propelled innovations in nanomedicine.Traditional fluorophores often suffer from aggregationcaused quenching(ACQ).On the contrary,AIEgens exhibit intense emission upon aggregation,alongside advantageous properties,including minimal background interference,high photostability,as well as multifunctional therapeutic capabilities(such as photothermal therapy,PTT;photodynamic therapy,PDT;and sonodynamic therapy,SDT).Moreover,their exceptional biocompatibility positions them as promising agents for tumor immunotherapy.This review offers a thorough examination of how AIEgens enhance antitumor immunity through mechanisms such as immunogenic cell death(ICD),apoptosis,and pyroptosis,which collectively activate immune cells,reprogram the immunosuppressive tumor microenvironment(TME),suppress tumor proliferation,and mitigate metastasis and recurrence.By highlighting these advances,we aim to stimulate further research into the development of next-generation AIEgens for broader immunological applications and to promote their clinical translation.展开更多
Second near-infrared window(NIR-II,1000–1700 nm)imaging is emerging as a powerful tool in biomedical research,offering unparalleled advantages for deeptissue,high-contrast,and low-autofluorescence visualization.In th...Second near-infrared window(NIR-II,1000–1700 nm)imaging is emerging as a powerful tool in biomedical research,offering unparalleled advantages for deeptissue,high-contrast,and low-autofluorescence visualization.In the context of viral infections,which remain one of the most persistent global health threats,NIR-II-based technologies have demonstrated transformative potential for real-time diagnosis,immune response tracking,and precision therapy.In this review,we highlight recent advances in NIR-II fluorescence imaging and theranostic platforms across various viral models,including SARS-CoV-2,hepatitis C virus,rabies virus,monkeypox virus,and Japanese encephalitis virus.We discuss how NIR-II imaging has enabled the dynamic visualization of viral RNA structures,host–pathogen interactions,inflammatory signaling,and lesion-targeted treatment using light-activated photodynamic or photothermal therapy.We further examined strategies for enhancing tissue penetration,viral specificity,and delivery across biological barriers,such as the blood–brain barrier.Finally,we outline the current challenges in probe development,biosafety,and clinical translation and propose future directions where NIR-II technology may reshape viral diagnostics,outbreak surveillance,and vaccine response evaluation.Together,these insights establish NIR-II imaging not only as a next-generation optical modality but also as a versatile platformfor combating viral diseaseswith unprecedented precision.展开更多
Near-infrared(NIR)phototheranostics(PTs)show higher tissue penetration depth,signal-to-noise ratio,and better biosafety than PTs in the ultraviolet and visible regions.However,their further advancement is severely hin...Near-infrared(NIR)phototheranostics(PTs)show higher tissue penetration depth,signal-to-noise ratio,and better biosafety than PTs in the ultraviolet and visible regions.However,their further advancement is severely hindered by poor performances and short-wavelength absorptions/emissions of PT agents.Among reported PT agents,conjugated small molecular nanoparticles(CSMNs)prepared from D-A-typed photoactive conjugated small molecules(CSMs)have greatly mediated this deadlock by their high photostability,distinct chemical structure,tunable absorption,intrinsic multifunctionality,and favorable biocompatibility,which endows CSMNs with more possibilities in biological applications.This review aims to introduce the recent progress of CSMNs for NIR imaging,therapy,and synergistic PTs with a comprehensive summary of their molecular structures,structure types,and optical properties.Moreover,the working principles of CSMNs are illustrated from photophysical and photochemical mechanisms and light-tissue interactions.In addition,molecular engineering and nanomodulation approaches of CSMs are discussed,with an emphasis on strategies for improving performances and extending absorption and emission wavelengths to the NIR range.Furthermore,the in vivo investigation of CSMNs is illustrated with solid examples from imaging in different scenarios,therapy in 2 modes,and synergistic PTs in combinational functionalities.This review concludes with a brief conclusion,current challenges,and future outlook of CSMNs.展开更多
Rabies is a fatal central nervous system(CNS)infection caused by the rabies virus(RABV),with a clinical fatality rate approaching 100%[1].Once symptoms appear,effective treatments are virtually nonexistent,posing a se...Rabies is a fatal central nervous system(CNS)infection caused by the rabies virus(RABV),with a clinical fatality rate approaching 100%[1].Once symptoms appear,effective treatments are virtually nonexistent,posing a serious global health threat.Although various prevention measures,such as prophylactic vaccination and post-exposure prophylaxis(PEP)[2],have helped reduce incidence rates,especially in developed countries,several limitations remain.PEP is highly time-sensitive and largely ineffective once the virus invades the CNS.Moreover,rabies immunoglobulin is costly and scarce,limiting its use in resource-limited settings[3].展开更多
Nanotherapeutics has an increasing role in the treatment of diseases such as cancer. In photodynamic therapy （PDT） a therapeutically inactive photosensitizer compound is selectively activated by light to produce mol...Nanotherapeutics has an increasing role in the treatment of diseases such as cancer. In photodynamic therapy （PDT） a therapeutically inactive photosensitizer compound is selectively activated by light to produce molecules capable of killing diseased cells and pathogens. A phototheranostic agent can be defined as a single nanoentity with the capabilities for targeted delivery, optical imaging and photodynamic treatment of a disease. Malignant cells, tissue and microbial etiologic agents can be effectively targeted by PDT. Photodynamic therapy is noninvasive, or minimally invasive, and has few side effects as damage to healthy tissue is minimized and the killing effect is localized. Various forms of cancer, acne and other diseases may be treated. The in vivo efficacy of photosensitizers is further improved by attaching them to nanostructures capable of targeting the diseased site. Such photosensitizer-functionalized nanostructures, or nano- therapeutics, allow site-specific delivery of imaging and therapeutic agents for improved phototheranostic performance. This review explores the potential applications of phototheranostic nanostructures in diagnosis and therapy.展开更多
Cancer phototheranostics involving optical imaging-guided photodynamic therapy(PDT)and photothermal therapy(PTT)is a localized noninvasive approach in treating cancer.Mitochondria-targeted near-infrared(NIR)cyanines a...Cancer phototheranostics involving optical imaging-guided photodynamic therapy(PDT)and photothermal therapy(PTT)is a localized noninvasive approach in treating cancer.Mitochondria-targeted near-infrared(NIR)cyanines are excellent therapeutic photosensitizers of cancer.However,most mitochondria-targeted cyanines exist in the form of hydrophobic structures,which in vivo may cause cyanine aggregation during blood circulation,resulting in poor biocompatibility and limited therapeutic efficacy.Therefore,we developed a trade-off strategy by encapsulating mitochondria-targeted cyanines into liposomal bilayers(CyBI7-LPs),which balanced hydrophilicity that favored blood circulation and hydrophobicity that enhanced mitochondria tumor targeting.Moreover,CyBI7-LPs greatly minimized photobleaching of cyanine as self-generated reactive oxygen species(ROS)could rapidly escape from the liposomal bilayer,affording enhanced PTT/PDT efficacy.Bioorthogonal-mediated targeting strategy was further employed to improve uptake of tumor cells by modifying the liposomal surface to generate CyBI7-LPB.The CyBI7-LPB probe produced a tumor-to-background ratio(TBR)of approximately 6.4 at 24 HPI.Guiding by highly sensitive imaging resulted in excellent anti-tumor therapy outcomes using CyBI7-LPB due to the enhanced photothermal and photodynamic effects.This proposed liposomal nanoplatform exhibited a simple and robust approach as an imaging-guided synergistic anti-tumor therapeutic strategy.展开更多
Optical imaging and phototherapy in the second near-infrared window(NIR-Ⅱ, 900–1700 nm) can reduce tissue auto-fluorescence and photon scattering, which facilitates higher spatial resolution and deeper tissue penetr...Optical imaging and phototherapy in the second near-infrared window(NIR-Ⅱ, 900–1700 nm) can reduce tissue auto-fluorescence and photon scattering, which facilitates higher spatial resolution and deeper tissue penetration depth for solid tumor theranostics. Herein, a polycyclic naphthalenediimide(NDI) based chromophore 13-amino-4,5-dibromo-2,7-di(dodecan-6-yl)-1 H-isoquinolino[4,5,6-fgh]naphtho[1,8-bc][1,9]phenanthroline-1,3,6,8(2H,7H,9H)-tetraone(NDI-NA) was designed and synthesized. With large polycyclic π-systems, NDI-NA molecule possesses broad near-infrared(NIR) absorption(maximum at777 nm) and emission(maximum at 921 nm). By nanoprecipitation, NDI-NA nanoparticles(NPs) were formed in aqueous solution with J-aggregative state, which showed huge red-shift in both absorption spectrum(maximum at 904 nm) and emission spectrum(maximum at 1,020 nm), endowing NDI-NA NPs efficient NIR-Ⅱ fluorescence imaging capability. Besides, the NPs present effective tumor-targeting capability in vivo based on the enhanced permeation and retention(EPR) effect. More importantly, NDI-NA NPs simultaneously have high photothermal conversion efficiency(30.8%) and efficient reactive oxygen species generation ability, making them remarkably phototoxic to cancer cells. The polycyclic chromophore based multifunctional NDI-NA NPs as NIR-Ⅱ phototheranostic agents possess bright future for clinical NIR-Ⅱ imaging-guided cancer phototherapy.展开更多
Although metal-based chemical agents have demonstrated promising bacteriostatic effects in phototherapy,their short excitation/emission wavelengths and inadequate phototherapy efficiencies make their application in vi...Although metal-based chemical agents have demonstrated promising bacteriostatic effects in phototherapy,their short excitation/emission wavelengths and inadequate phototherapy efficiencies make their application in vivo difficult.We therefore synthesized a novel Pt(Ⅱ)metallacycle(Pt1110)that can be activated with a 980 nm laser for photodiagnosis/treatment in deep tissue.We found that Pt1110 significantly improved photothermal conversion(95%improvement)and ^(1)O_(2) generation(ΦΔ75%increase)compared to the ligand itself 1 and was well capable of light-induced sterilization under safe laser irradiation(0.72 W/cm^(2)).In addition,Pt1110 has little to no toxicity to cells.After incorporated into liposome,Pt1110 NPs was effective in wound healing in infection and keratitis models upon laser irradiation,which was accurately observed by NIR-Ⅱfluorescence imaging.This novel metal-coordinated supramolecular material has a potential to become a universal platform for phototherapy in deep tissue.展开更多
基金supported by the Natural Science Foundation of Zhejiang Province(Nos.LZ23B040001,LY23E030003 and LY24B030005)the National Natural Science Foundation of China(No.22105222)+1 种基金the Interdisciplinary Research Project of Hangzhou Normal University(No.2024JCXK05)the Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application,Soochow University。
文摘The integration of advanced diagnostic and therapeutic capabilities in oncology has given rise to phototheranostics,a field that combines the precision of imaging with the selectivity of light-activated treatments.Due to their pronounced near-infrared(NIR)absorption,tunable molecular structures,and commendable stability,organic photovoltaic non-fullerene acceptors(NFAs)represent a promising frontier in cancer management.Despite the great potential of NFAs in phototheranostics,there is currently a lack of systematic reviews in this field.This review provides a meticulous examination of the current state of NFAs in the field of phototheranostics,highlighting the strategic approaches to spectral red-shifting that enhance tissue penetration and therapeutic efficacy.It dissects the link between molecular architecture and performance across key therapeutic and diagnostic modalities,including photothermal therapy(PTT),photodynamic therapy(PDT),and fluorescence imaging(FLI).In addition,the review presents a concise analysis of the challenges and milestones in the clinical translation of NFAs,offering insights into the innovations required to overcome existing barriers.
基金the National Natural Science Foundation of China(grant nos.82302257,82302356,62288102,and 22465015)the Natural Science Foundation of Jiangxi Province(grant nos.20232BAB203049,20243BCE51136,20212BAB214005,and 20224BAB204007)+2 种基金the project funded by China Postdoctoral Science Foundation(grant no.2023M730603)the Natural Science Foundation of Fujian Province(grant no.2023J01529)the innovation team of photoelectric functional materials and devices for biomedical theranostics of Fujian Normal University(grant no.Y07204080K13).
文摘Recently emerging Type-I photodynamic therapy holds significant promise in addressing the hypoxia challenge encountered by traditional oxygen-dependent Type-II photosensitizers(PSs)in photodynamic oncotherapy.The key hurdle in engineering Type-I PSs lies in enhancing the electron transfer capabilities of these molecules,enabling them to efficiently convert H_(2)O or oxygen-based substrates into reactive oxygen species.Herein,we propose to construct intramolecular electric fields in the second near-infrared(NIR-II)emissive organic PSs to regulate the local electron density for boosting hypoxia-tolerant cancer phototheranostics.Upon introducing the molecular cationization approach and electron programming strategy,the resultant cationic semiconducting architecture achieves electron distribution rearrangement,forms intramolecular electric fields,and facilitates electron transfer path,resulting in a 50-fold amplification of electrostatic potential difference,thereby accelerating the hydroxyl radical(•OH)-dominant Type-I photosensitization process.In vitro studies disclose that the tailor-made nanomaterial selectively targets the mitochondria and causesmitochondria-mediated cancer cell apoptosis under laser irradiation.Notably,this as-prepared nanoplatform enables NIR-II fluorescence imaging-assisted phototherapy and exhibits in vivo antitumor efficacy on 4T1-bearing mouse models.We believe that this contribution will launch the future of NIR-II emitting Type-I PSs and enlighten scientific researchers to exploit high-efficiency phototheranostic agents for cancer therapy.
基金National Natural Science Foundation of China(51873092,51961160730,and 51673150)the National Key R&D Program of China(Intergovernmental Cooperation Project,2017YFE0132200)+2 种基金Tianjin Science Fund for Distinguished Young Scholars(19JCJQJC61200)Key Public Relations Project funded by Tianjin Health and Family Planning Commission(16KG103)the Fundamental Research Funds for the Central Universities,Nankai University。
文摘Phototheranostics that concurrently and complementarily integrate real-time diagnosis and in situ therapeutic capabilities in one platform has become the advancing edge of precision medicine.Organic agents possess the merits of facile preparation,high purity,tunable photophysical property,good biocompatibility,and potential biodegradability,which have shown great promise for disease theranostics.This review summarizes the recent achievements of organic phototheranostic agents and applications,especially which rationally utilize energy dissipation pathways of Jablonski diagram to modulate the fluorescence emission,photoacoustic/photothermal production,and photodynamic processes.Of particular interest are the systems exhibiting huge differences in aggregate state as compared with the solution or single molecule form,during which the intramolecular motions play an important role in regulating the photophysical properties.The recent advances from such an aspect for biomedical applications including high-resolution imaging,activatable imaging and therapy,adaptive theranostics,image-guided surgery,immunotherapy,and afterglow imaging are discussed.A brief summary and perspective in this field are also presented.We hope this review will be helpful to the researchers interested in bioprobe design and theranostic applications,and inspire new insights into the linkage between aggregate science and biomedical field.
基金supported by the Natural Science Foundation of China (52122317, 22175120, 22101183, 22305049)Shenzhen Science and Technology Program (JCYJ20190808153415062,RCYX20200714114525101, 20220809130438001, JSGG20220606-141800001)the Natural Science Foundation for Distinguished Young Scholars of Guangdong Province (2020B1515020011)。
文摘Exploration of single molecular species synchronously featured by long excitation/emission wavelength, accurate diagnosis, and effective therapy, remains supremely appealing to implement high-performance cancer phototheranostics. However, those previously established phototheranostic agents are undiversified and stereotyped in terms of structural skeleton, and generally exhibit insufficient phototheranostic outcomes. Herein, we innovatively utilized indanone-condensed thiadiazolo[3,4-g]quinoxaline(ITQ) as electron acceptor to construct novel photosensitizer with second near-infrared(NIR-II) emission. Experimental study and theoretical calculation demonstrated that comparing with the counterparts constituting by widely employed NIR-II building block benzobisthiadiazole(BBTD) and 6,7-diphenylthiadiazoloquinoxaline(DPTQ), ITQ-based photosensitizer(TITQ) showed superior aggregation-induced emission(AIE) characteristics, much stronger type-I reactive oxygen species(ROS) production, and prominent photothermal conversion capacity. Furthermore, TITQ nanoparticles with excellent biocompatibility were capable of effectively accumulating in the tumor site and visualizing tumor through fluorescence-photoacoustic-photothermal trimodal imaging with highly spatiotemporal resolution, and completely eliminating tumor by type-I photodynamic-photothermal therapy.
基金The work was supported by the National Natural Science Foundation of China(NNSFC)(61525402,61775095)Natural Science Foundation of Jiangsu Province(BK20200092)+2 种基金Jiangsu Province Policy Guidance Plan(BZ2019014)Six talent peak innovation team in Jiangsu Province(TD-SWYY-009)“Taishan scholars”construction special fund of Shandong Province.
文摘Phototheranostics integrates deep-tissue imaging with phototherapy(containing photothermal therapy and photodynamic therapy),holding great promise in early diagnosis and precision treatment of cancers.Recently,second near-infrared(NIR-II)fluorescence imaging exhibits the merits of high accuracy and specificity,as well as real-time detection.Among the NIR-II fluorophores,organic small molecular fluorophores have shown superior properties in the biocompatibility,variable structure,and tunable emission wavelength than the inorganic NIR-II materials.What’s more,some small molecular fluorophores also display excellent cytotoxicity when illuminated with the NIR laser.This review summarizes the progress of small molecular NIR-II fluorophores with different central cores for cancer phototheranostics in the past few years,focusing on the molecular structures and phototheranostic performances.Furthermore,challenges and prospects of future development toward clinical translation are discussed.
基金the National Natural Science Foundation of China(Nos.22275096,W2432015)Natural Science Key Fund for Universities in Jiangsu Province(No.22KJA430007)Qinglan Project of Jiangsu Province of China。
文摘Broadband photothermal and photoacoustic agents in the near-infrared(NIR)biowindow are of significance for cancer phototheranostics.In this work,Pt Cu nanosheets with an average lateral size of less than 10 nm are synthesized as NIR photothermal and photoacoustic agents in vivo,which show strong light absorption from NIR-I to NIR-II biowindows with the photothermal conversion efficiencies of 20.4%under 808 nm laser and 32.7%under 1064 nm laser.Pt Cu nanosheets functionalized with folic acidmodified thiol-poly(ethylene glycol)(SH-PEG-FA)present good biocompatibility and 4T1 tumor-targeted effect,which give high-contrast photoacoustic imaging and efficient photothermal ablation of 4T1 tumor in both NIR-I and NIR-II biowindows.Our work significantly broadens applications of noble metal-based nanomaterials in the fields of cancer phototheranostics by rationally designing their structures and modulating their physicochemical properties.
基金financial support from the Training Program of the Major Research Plan of the National Natural Science Foundation of China (No. 91959123)National Natural Science Foundation of China (No. 22077092)+2 种基金Key Research and Development Program of Social Development of Jiangsu Province (No. BE2018655)the Open Project Program of the State Key Laboratory of Radiation Medicine and Protection (Nos. GZK1202132, GZK1202140 and GZK1202017)funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions。
文摘Phototheranostics have attracted tremendous attention in cancer diagnosis and treatment because of the noninvasiveness and promising effectiveness.Developing advanced phototheranostic agents with long emission wavelength,excellent biocompatibility,great tumor-targeting capability,and efficient therapeutic effect is highly desirable.However,the mutual constraint between imaging and therapeutic functions usually hinders their wide applications in biomedical field.To balance this contradiction,we herein rationally designed and synthesized three novel tumor-targeted NIR-Ⅱ probes(QR-2PEG_(321),QR-2PEG_(1000),and QR-2PEG_(5000)) by conjugating three different chain lengths of PEG onto an integrin α_(v)β_(3)-targeted NIR-Ⅱ heptamethine cyanine fluorophore,respectively.In virtue of the essential amphiphilic characteristics of PEG polymers,these probes display various degree of aggregation in aqueous buffer accompanying with differential NIR-Ⅱ imaging and photothermal(PTT) therapeutic performance.Both in vitro and in vivo results have demonstrated that probe QR-2PEG_(5000) has the best NIR-Ⅱ imaging performance with prominent renal clearance,whereas QR-2PEG_(321)possesses excellent photoacoustic signal as well as PTT effect,which undoubtedly provides a promising toolbox for tumor diagnosis and therapy.We thus envision that these synthesized probes have great potential to be explored as a toolkit for precise diagnosis and treatment of malignant tumors.
基金supported by the National Natural Science Foundation of China (No. 61775095)Natural Science Foundation of Jiangsu Province (No. BK20200092)+3 种基金Jiangsu Province Policy Guidance Plan (No. BZ2019014)Natural Science Foundation of Shandong Province (No. ZR2020KB018)‘Taishan scholars’ construction special fund of Shandong Provincethe High-Performance Computing Center in Nanjing Tech University for supporting the computational resources
文摘The small molecular second near-infrared(NIR-Ⅱ, 1000–1700 nm) dye-based nanotheranostics can concurrently combine deep-tissue photodiagnosis with in situ phototherapy, which occupies a vital position in the early detection and precise treatment of tumors. However, the development of small molecular NIR-Ⅱ dyes is still challenging due to the limited electron acceptors and cumbersome synthetic routes.Herein, we report a novel molecular electron acceptor, boron difluoride formazanate(BDF). Based on BDF, a new small molecular NIR-Ⅱ dye BDF1005 is designed and synthesized with strong NIR-I absorption at 768 nm and bright NIR-Ⅱ peak emission at 1034 nm. In vitro and in vivo experiments demonstrate that BDF1005-based nanotheranostics can be applied for NIR-Ⅱ fluorescence imaging-guided photothermal therapy of 4T1 tumor-bearing mice. Under 808 nm laser irradiation, tumor growth can be effectively inhibited. This work opens up a new road for the exploitation of NIR-Ⅱ small molecular dyes for cancer phototheranostics.
基金financially supported in part by the National Natural Science Foundation of China(Nos.62075103,81973488)the Natural Science Foundation of Jiangsu Province(No.BK20211271)+4 种基金the Foundation of Anhui Province Key Laboratory of Pharmaceutical Preparation Technology and Application(No.2021KFKT07)the Training Program of Innovation and Entrepreneurship for College Students in Jiangsu(No.202110312037Z)the Jiangsu Provincial Medical Youth Talent(No.QNRC2016075)the Nanjing Medical Science and Technique Development Foundation(No.ZKX19022)the Jiangsu Provincial High level Health Talent“six one project”(No.LGY2019005)。
文摘Phototheranostic with highly integrated functions is an attractive platform for cancer management. It remains challenging to develop a facile phototheranostic platform with complementary bimodal imaging and combinational therapy capacity. Herein, the small-molecule cyanine IR780 loaded liposomes have been harnessed as a nanoplatform to simultaneously realize photoacoustic(PA)/the second near-infrared window(NIR-Ⅱ) fluorescence imaging and image-guided surgery/adjuvant photothermal therapy(PTT).This nanoplatform exhibits attractive properties like uniform controllable size, stable dispersibility, NIR-Ⅱ fluorescence emission, photothermal conversion, and biocompatibility. Benefiting from the complementary PA/NIR-Ⅱ fluorescence bimodal imaging, this nanoplatform was successfully applied in precise vasculature delineation and tumor diagnosis. Interestingly, the tumor was clearly detected by NIR-Ⅱ fluorescence imaging with the highest tumor-to-normal-tissue ratio up to 12.69, while signal interference from the liver was significantly reduced, due to the difference in the elimination rate of the nanoplatform in the liver and tumor. Under the precise guidance of the image, the tumor was accurately resected, and the simulated residual lesion after surgery was completely ablated by adjuvant PTT. This combined therapy showed improved antitumor efcacy over the individual surgery or PTT. This work develops a facile phototheranostic nanoplatform with great significance in accurately diagnosing and effectively treating tumors using simple NIR light irradiation.
基金the National Natural Science Foundation of China(No.82371613 to F.S.)the National Key Research and Development Program of China(No.2021YFC2700200 to F.S.)+5 种基金the Key Research and Development Program of Zhejiang Province(No.2023C03035 to F.S.)the Key Research and Development Program of Ningxia Hui Autonomous Region(No.2021BEG02029 to F.S.)the 2024 Zhejiang Medicine and Health Technology Plan(No.2024KY100 to X.Y.)the 2024 Zhejiang Traditional Chinese Medicine Science and Technology Plan(No.2024ZL597 to X.Y.)the Zhejiang Provincial Natural Science Foundation of China(No.LQ24H180003 to X.Y.)the 2023 Clinical Medical Research Special Key Project Fund of the Zhejiang Medical Association(2023ZYC-Z05 to X.Y.)for financial support.
文摘Human papillomavirus(HPV)is a highly prevalent venereal pathogen accounting for genital warts and various cancers like cervical,anal,and oropharyngeal cancers.Although imiquimod,a topical medication,is commonly used to treat genital warts induced by HPV,its potential as an in situ immune response regulator for HPV-related cancers has rarely been explored.In this study,we developed an innovative synergistic therapeutic platform by integrating near-infrared-II(NIR-II)absorbing aggregationinduced emission(AIE)agent(TPE-BT-BBTD)and imiquimod into an injectable hydrogel named TIH.TPE-BT-BBTD molecule that serves as a photothermal agent,with exposure to a 1064 nm laser,effectively destroys tumor cells and releases tumor-related antigens.During the thermogenesis process,the hydrogel melts and releases imiquimod.The released imiquimod,in conjunction with the dead tumor antigens,stimulates dendritic cellmaturation,activating the immune system to ultimately eliminate residual cancer cells.This novel approach combines the immunomodulatory effects of imiquimod with a 1064 nm-excitable photothermal agent in a hydrogel delivery system,offering a promising tactic for combating HPV-associated cancers.
文摘Tuberculosis(TB)infection,caused by Mycobacterium tuberculo-sis,reveals tens of millions of new cases and causes millions of deaths each year.The traditional clinical treatment for TB is long-term and combined usage of antibiotics but suffers from poor lesion and pathogen targeting,insufficient efficacy,high systemic toxicity,and ineffectiveness against drug-resistant M.tuberculosis.As a characteristic lesion of TB,granulomas have a compact construction,which greatly limits the access of small-molecule antibiotics to the necrotic area to kill M.tuberculosis[1].
基金partially supported by the National Natural Science Foundation of China(52122317,22175120,22307080)the Shenzhen Science and Technology Program(RCBS20221008093224016,JCYJ20220531101201003,20220809130438001)+4 种基金the Guangdong Basic and Applied Basic Research Fund(2023A1515010558)the Pearl River Talent Recruitment Program(2019QN01Y103)Medical-Engineering Interdisciplinary Research Foundation of Shenzhen University(2023YG021)the Medicine Plus Program of Shenzhen University(2024YG004)Research Team Cultivation Program of Shenzhen University(2023QNT003).
文摘Aggregation-induced emission luminogens(AIEgens)have been prosperously developed and applied in the fields of optical imaging and theranostics since its establishment.Nowadays,AIEgens can fulfill nearly all requirements in optical imaging and theranostics with emission spectra ranging from visible to near-infrared wavelengths.Although a variety of AIEgens with varying wavelengths and functionalities have been continuously designed,their performance is heavily dependent on the use of conventional light sources,such as xenon lamps and lasers,which severely hinder further applications due to limited penetration depth and background autofluorescence in biological tissues.To mitigate these limitations and maximize the potential of AIEgens,unconventional excitation sources such as chemical energy,ultrasound,and X-ray offer effective alternatives that circumvent the drawbacks associated with traditional light-based constant excitation.In this Review,we introduce the fundamental principles governing the combination of unconventional excitation sources with AIEgens,highlight recent advancements in using AIEgens excited by these unconventional sources for bioimaging and theranostics,and discuss current challenges and future perspectives aimed at advancing the biomedical applications of AIEgens.
基金the National Key Research and Development Program of China(2023YFB3810001,2024YFA1212100)the Science and Technology Foundation of Shenzhen City(JCYJ20241202124423032,20220809130438001)the Pearl River Talent Recruitment Program(2019QN01Y103).
文摘Cancer immunotherapy is a groundbreaking treatment that utilizes the body’s immune system to fight against cancers.Despite the clinical application of several immunotherapeutic agents,challenges persist,including limited patient responsiveness and adverse events stemming from immune activation,which constrain overall efficacy.Recent advances in aggregation-induced emission luminogens(AIEgens)have propelled innovations in nanomedicine.Traditional fluorophores often suffer from aggregationcaused quenching(ACQ).On the contrary,AIEgens exhibit intense emission upon aggregation,alongside advantageous properties,including minimal background interference,high photostability,as well as multifunctional therapeutic capabilities(such as photothermal therapy,PTT;photodynamic therapy,PDT;and sonodynamic therapy,SDT).Moreover,their exceptional biocompatibility positions them as promising agents for tumor immunotherapy.This review offers a thorough examination of how AIEgens enhance antitumor immunity through mechanisms such as immunogenic cell death(ICD),apoptosis,and pyroptosis,which collectively activate immune cells,reprogram the immunosuppressive tumor microenvironment(TME),suppress tumor proliferation,and mitigate metastasis and recurrence.By highlighting these advances,we aim to stimulate further research into the development of next-generation AIEgens for broader immunological applications and to promote their clinical translation.
基金financial support from National Research Foundation of Korea(2018R1A3B1052702,JSK)China Scholarship Council(CSC,202106270027,QD).
文摘Second near-infrared window(NIR-II,1000–1700 nm)imaging is emerging as a powerful tool in biomedical research,offering unparalleled advantages for deeptissue,high-contrast,and low-autofluorescence visualization.In the context of viral infections,which remain one of the most persistent global health threats,NIR-II-based technologies have demonstrated transformative potential for real-time diagnosis,immune response tracking,and precision therapy.In this review,we highlight recent advances in NIR-II fluorescence imaging and theranostic platforms across various viral models,including SARS-CoV-2,hepatitis C virus,rabies virus,monkeypox virus,and Japanese encephalitis virus.We discuss how NIR-II imaging has enabled the dynamic visualization of viral RNA structures,host–pathogen interactions,inflammatory signaling,and lesion-targeted treatment using light-activated photodynamic or photothermal therapy.We further examined strategies for enhancing tissue penetration,viral specificity,and delivery across biological barriers,such as the blood–brain barrier.Finally,we outline the current challenges in probe development,biosafety,and clinical translation and propose future directions where NIR-II technology may reshape viral diagnostics,outbreak surveillance,and vaccine response evaluation.Together,these insights establish NIR-II imaging not only as a next-generation optical modality but also as a versatile platformfor combating viral diseaseswith unprecedented precision.
基金financially supported by the Research Start-up Funds of Northwestern Polytechnical University(23GH02025)the Postdoctoral Innovative Talent Support Program(W016336)the Fundamental Science Center Foundation of China(D5110220297).
文摘Near-infrared(NIR)phototheranostics(PTs)show higher tissue penetration depth,signal-to-noise ratio,and better biosafety than PTs in the ultraviolet and visible regions.However,their further advancement is severely hindered by poor performances and short-wavelength absorptions/emissions of PT agents.Among reported PT agents,conjugated small molecular nanoparticles(CSMNs)prepared from D-A-typed photoactive conjugated small molecules(CSMs)have greatly mediated this deadlock by their high photostability,distinct chemical structure,tunable absorption,intrinsic multifunctionality,and favorable biocompatibility,which endows CSMNs with more possibilities in biological applications.This review aims to introduce the recent progress of CSMNs for NIR imaging,therapy,and synergistic PTs with a comprehensive summary of their molecular structures,structure types,and optical properties.Moreover,the working principles of CSMNs are illustrated from photophysical and photochemical mechanisms and light-tissue interactions.In addition,molecular engineering and nanomodulation approaches of CSMs are discussed,with an emphasis on strategies for improving performances and extending absorption and emission wavelengths to the NIR range.Furthermore,the in vivo investigation of CSMNs is illustrated with solid examples from imaging in different scenarios,therapy in 2 modes,and synergistic PTs in combinational functionalities.This review concludes with a brief conclusion,current challenges,and future outlook of CSMNs.
文摘Rabies is a fatal central nervous system(CNS)infection caused by the rabies virus(RABV),with a clinical fatality rate approaching 100%[1].Once symptoms appear,effective treatments are virtually nonexistent,posing a serious global health threat.Although various prevention measures,such as prophylactic vaccination and post-exposure prophylaxis(PEP)[2],have helped reduce incidence rates,especially in developed countries,several limitations remain.PEP is highly time-sensitive and largely ineffective once the virus invades the CNS.Moreover,rabies immunoglobulin is costly and scarce,limiting its use in resource-limited settings[3].
文摘Nanotherapeutics has an increasing role in the treatment of diseases such as cancer. In photodynamic therapy （PDT） a therapeutically inactive photosensitizer compound is selectively activated by light to produce molecules capable of killing diseased cells and pathogens. A phototheranostic agent can be defined as a single nanoentity with the capabilities for targeted delivery, optical imaging and photodynamic treatment of a disease. Malignant cells, tissue and microbial etiologic agents can be effectively targeted by PDT. Photodynamic therapy is noninvasive, or minimally invasive, and has few side effects as damage to healthy tissue is minimized and the killing effect is localized. Various forms of cancer, acne and other diseases may be treated. The in vivo efficacy of photosensitizers is further improved by attaching them to nanostructures capable of targeting the diseased site. Such photosensitizer-functionalized nanostructures, or nano- therapeutics, allow site-specific delivery of imaging and therapeutic agents for improved phototheranostic performance. This review explores the potential applications of phototheranostic nanostructures in diagnosis and therapy.
基金This work was supported by the National Key Research and Development Program of China(Nos.2017YFC1309100 and 2017YFA0205200)National Natural Science Foundation of China(Nos.81671753,91959124,81227901,and 21804104)+4 种基金Natural Science Foundation of Shaanxi Province of China(No.2020PT-020)Key Research and Development Program of Shaanxi Province(2019NY-085)Natural Science Basic Research Program of Shaanxi Province of China(Nos.2019JQ-139,2019JQ-662,2018JM2041)the Fundamental Research Funds for the Central Universities(Nos.JB191211,JB191207,JB191208)the Open Project Program of the State Key Laboratory of Cancer Biology(Fourth Military Medical University)(No.CBSKL2019ZDKF06).
文摘Cancer phototheranostics involving optical imaging-guided photodynamic therapy(PDT)and photothermal therapy(PTT)is a localized noninvasive approach in treating cancer.Mitochondria-targeted near-infrared(NIR)cyanines are excellent therapeutic photosensitizers of cancer.However,most mitochondria-targeted cyanines exist in the form of hydrophobic structures,which in vivo may cause cyanine aggregation during blood circulation,resulting in poor biocompatibility and limited therapeutic efficacy.Therefore,we developed a trade-off strategy by encapsulating mitochondria-targeted cyanines into liposomal bilayers(CyBI7-LPs),which balanced hydrophilicity that favored blood circulation and hydrophobicity that enhanced mitochondria tumor targeting.Moreover,CyBI7-LPs greatly minimized photobleaching of cyanine as self-generated reactive oxygen species(ROS)could rapidly escape from the liposomal bilayer,affording enhanced PTT/PDT efficacy.Bioorthogonal-mediated targeting strategy was further employed to improve uptake of tumor cells by modifying the liposomal surface to generate CyBI7-LPB.The CyBI7-LPB probe produced a tumor-to-background ratio(TBR)of approximately 6.4 at 24 HPI.Guiding by highly sensitive imaging resulted in excellent anti-tumor therapy outcomes using CyBI7-LPB due to the enhanced photothermal and photodynamic effects.This proposed liposomal nanoplatform exhibited a simple and robust approach as an imaging-guided synergistic anti-tumor therapeutic strategy.
基金supported by Jiangsu Provincial Key Research and Development Plan (BE2017741)Natural Science Foundation of Jiangsu Province (BK20180136, BK20160051)+1 种基金Jiangsu Provincial Medical Youth Talent (QNRC 2016121)Nanjing Foundation for Development of Science and Technology (2017sc512031, 201605042)。
文摘Optical imaging and phototherapy in the second near-infrared window(NIR-Ⅱ, 900–1700 nm) can reduce tissue auto-fluorescence and photon scattering, which facilitates higher spatial resolution and deeper tissue penetration depth for solid tumor theranostics. Herein, a polycyclic naphthalenediimide(NDI) based chromophore 13-amino-4,5-dibromo-2,7-di(dodecan-6-yl)-1 H-isoquinolino[4,5,6-fgh]naphtho[1,8-bc][1,9]phenanthroline-1,3,6,8(2H,7H,9H)-tetraone(NDI-NA) was designed and synthesized. With large polycyclic π-systems, NDI-NA molecule possesses broad near-infrared(NIR) absorption(maximum at777 nm) and emission(maximum at 921 nm). By nanoprecipitation, NDI-NA nanoparticles(NPs) were formed in aqueous solution with J-aggregative state, which showed huge red-shift in both absorption spectrum(maximum at 904 nm) and emission spectrum(maximum at 1,020 nm), endowing NDI-NA NPs efficient NIR-Ⅱ fluorescence imaging capability. Besides, the NPs present effective tumor-targeting capability in vivo based on the enhanced permeation and retention(EPR) effect. More importantly, NDI-NA NPs simultaneously have high photothermal conversion efficiency(30.8%) and efficient reactive oxygen species generation ability, making them remarkably phototoxic to cancer cells. The polycyclic chromophore based multifunctional NDI-NA NPs as NIR-Ⅱ phototheranostic agents possess bright future for clinical NIR-Ⅱ imaging-guided cancer phototherapy.
基金supported by National Natural Science Foundation of China(22022404,22074050,21904103)the Fundamental Research Funds for the Central Universities(CCNU22QN007)+4 种基金the Open Research Fund of State Key Laboratory of Chemo/Biosensing and Chemometrics(2021005)the Ministry of Education Key Laboratory for the Synthesis and Application of Organic Functional Molecules Hubei University(KLSAOFM2111)the Opening Project of Key Laboratory of Optoelectronic Chemical Materials and Devices of Ministry of Education,Jianghan University(JDGD-202209)the Open Project Program of Key Laboratory for Analytical Science of Food Safety and Biology,Ministry of Education(FS2202)supported by the CRI project of National Research Foundation of Republic of Korea(2018R1A3B1052702,JSK)。
文摘Although metal-based chemical agents have demonstrated promising bacteriostatic effects in phototherapy,their short excitation/emission wavelengths and inadequate phototherapy efficiencies make their application in vivo difficult.We therefore synthesized a novel Pt(Ⅱ)metallacycle(Pt1110)that can be activated with a 980 nm laser for photodiagnosis/treatment in deep tissue.We found that Pt1110 significantly improved photothermal conversion(95%improvement)and ^(1)O_(2) generation(ΦΔ75%increase)compared to the ligand itself 1 and was well capable of light-induced sterilization under safe laser irradiation(0.72 W/cm^(2)).In addition,Pt1110 has little to no toxicity to cells.After incorporated into liposome,Pt1110 NPs was effective in wound healing in infection and keratitis models upon laser irradiation,which was accurately observed by NIR-Ⅱfluorescence imaging.This novel metal-coordinated supramolecular material has a potential to become a universal platform for phototherapy in deep tissue.
