The authors regret the inadvertent error was found in Fig.7 where the merged rows of the images were reversed due to carelessness and negligence.The corrected Fig.7 is presented below.The authors confirm that this cor...The authors regret the inadvertent error was found in Fig.7 where the merged rows of the images were reversed due to carelessness and negligence.The corrected Fig.7 is presented below.The authors confirm that this correction does not affect the conclusion of the study.展开更多
The authors regret the inadvertent error was found in Fig.7 where the merged rows of the images were reversed due to carelessness and negligence.The corrected Fig.7 is presented below.The authors confirm that this cor...The authors regret the inadvertent error was found in Fig.7 where the merged rows of the images were reversed due to carelessness and negligence.The corrected Fig.7 is presented below.The authors confirm that this correction does not affect the conclusion of the study.展开更多
Hepatic fibrosis is regulated by the synergistic actions of various cells and cytokines,with the activation and proliferation of hepatic stellate cells(HSCs) being considered the central event in this process.To achie...Hepatic fibrosis is regulated by the synergistic actions of various cells and cytokines,with the activation and proliferation of hepatic stellate cells(HSCs) being considered the central event in this process.To achieve specific targeting of activated hepatic stellate cells(a HSCs) and precise treatment of hepatic fibrosis,this study developed a dual-functional drug delivery system(SIL/c RGD-PEG-PPS PMs) with both targeting and responsive release capabilities.It aims to target the αvβ 3 receptor specifically expressed on the surface of a HSCs using the cyclic peptide c(RGDyk),and to exploit the high reactive oxygen species(ROS) level in the cellular microenvironment to achieve concentrated burst release of drugs at the pathological sites of hepatic fibrosis.Based on multiple assessments,SIL/c RGD-PEG-PPS PMs specifically enhanced the targeted delivery of silybin(SIL) to a HSCs,inhibited the proliferation and migration of a HSCs,and exhibited good biosafety.Additionally,it demonstrated excellent anti-fibrotic activity in fibrotic mice.In summary,this study shows great potential in targeted treatment of hepatic fibrosis and provides a multifunctional tool for advancing the research and therapeutic strategies of hepatic fibrosis.展开更多
The applications of supramolecular metal-peptide assemblies as catalyst or catalyst precursor have recent attracted increasing attentions.In this work,a fragment of the amyloid β-peptide,NH_(2)-KLVFF-COOH,was assembl...The applications of supramolecular metal-peptide assemblies as catalyst or catalyst precursor have recent attracted increasing attentions.In this work,a fragment of the amyloid β-peptide,NH_(2)-KLVFF-COOH,was assembled into nanofilms with encapsulated Pd,Pt and Au nanoparticles(NPs)via a one-step room temperature electron induction method.The effects of building block,intermolecular interaction,driving force and side-chain on the assembly were investigated.The assembly mechanism was thereby proposed.The crosslinking of peptide monomers results in mainly random and unordered structures.The obtained metal-peptide assemblies are extremely stable in water at neutral pH for long term.However,the metal NPs are able to be responsively released under basic and reductive conditions.The released NPs show a high activity to catalyze the reduction of 4-nitrophenol.The present studies on assembly mechanism and responsive release will be helpful for the design of organic skeletons and also for the future development of peptide stabilized metallic NPs with applications beyond catalysts.展开更多
In this research;the release of 5-Fluorouracil (5-FU) from different ionically crosslinked alginate (Alg) beads was investigated by using Fe3+, Al3+, Zn2+, and Ca2+, ions as crosslinking agent. The prepared beads were...In this research;the release of 5-Fluorouracil (5-FU) from different ionically crosslinked alginate (Alg) beads was investigated by using Fe3+, Al3+, Zn2+, and Ca2+, ions as crosslinking agent. The prepared beads were characterized by Fourier Transform Infrared Spectroscopy (FTIR) Differential Scanning Calorimetry (DSC) and Scanning Electron Micros-copy (SEM). The drug release studies were carried out at three pH values 1.2, 6.8 and 7.4 respectively each for two hours. The effects of the preparation conditions as crosslinker type, drug/polymer (w/w) ratio, crosslinker concentration and time of exposure to crosslinker on the release of 5-FU were investigated for 6 hours at 37℃. It was observed that 5-FU release from the beads followed the order of Fe > Zn > Al > Ca-Alg and increased with increasing drug/polymer ratio. At the end of 6 hours, the highest 5-FU release was found to be 90% (w/w) for Fe-Alg beads at the drug/polymer ratio of 1/8 (w/w), crosslinker concentration of 0.05 M, exposure time of 10 minutes respectively. The swelling measurements of the beads supported the release results. Release kinetics was described by Fickian and non-Fickian approaches.展开更多
Photoactivatable carbon monoxide-releasing molecules(photoCORMs)have provided a unique opportunity for the manipulation of the highly toxic but physiologically relevant CO gas.Here we describe an operationally simple ...Photoactivatable carbon monoxide-releasing molecules(photoCORMs)have provided a unique opportunity for the manipulation of the highly toxic but physiologically relevant CO gas.Here we describe an operationally simple and efficient one-pot solid-phase synthesis strategy for peptides with azopyridine(azpy)side-chains enabled by the on-resin Mills reaction.展开更多
Despite the synergy of immune checkpoint blockade(ICB) therapy and photodynamic therapy(PDT) holds great promise as countermeasures against breast cancer, exploring long-term or flexible short-time therapeutic strateg...Despite the synergy of immune checkpoint blockade(ICB) therapy and photodynamic therapy(PDT) holds great promise as countermeasures against breast cancer, exploring long-term or flexible short-time therapeutic strategies in “cold” tumors remains a great challenge. Here, we present a polyunsaturated fatty acid-doped liposomal hydrogel Lp(DHA)@CP Gel loaded with photosensitizer chlorin e6(Ce6) and programmed death-ligand 1 antibody(αPD-L1) for flexible local photoimmunotherapy with merely singledosed administration. The presence of polyunsaturated fatty acid(docosahexaenoic acid, DHA) doped in particle membrane endows liposomes with flexibly reactive oxygen species(ROS)-responsive release capability, which was attributed to the presence of abundant unsaturated groups. The αPD-L1 was repeatedly induced to in situ release in response to the PDT under photo-exposure. The immunogenic cell death(ICD) effect of PDT evoked “cold” breast tumor to “hot” one, and then assisted the cascade releasedαPD-L1 to synergistically boost the immunotherapy. After a single dose of peritumoral administration of Lp(DHA)@CP Gel, the on-demand treatment can maximize patient compliance and safety by adjusting therapeutic behaviors via a photo on-off switch. This work presents a flexible medication platform,showing promise in improving the objective response rate of ICB therapy and minimizing its systemic toxicity.展开更多
The irregular defects and residual tumor tissue after surgery are challenges for effective breast cancer treatment.Herein,a smart hydrogel with self-adaptable size and dual responsive cargos release was fabricated to ...The irregular defects and residual tumor tissue after surgery are challenges for effective breast cancer treatment.Herein,a smart hydrogel with self-adaptable size and dual responsive cargos release was fabricated to treat breast cancer via accurate tumor elimination,on-demand adipose tissue regeneration and effective infection inhibition.The hydrogel consisted of thiol groups ended polyethylene glycol(SH-PEG-SH)and doxorubicin encapsulated mesoporous silica nanocarriers(DOX@MSNs)double crosslinked hyaluronic acid(HA)after loading of antibacterial peptides(AP)and adipose-derived stem cells(ADSCs).A pH-cleavable unsaturated amide bond was pre-introduced between MSNs and HA frame to perform the tumor-specific acidic environment dependent DOX@MSNs release,meanwhile an esterase degradable glyceryl dimethacrylate cap was grafted on MSNs,which contributed to the selective chemotherapy in tumor cells with over-expressed esterase.The bond cleavage between MSNs and HA would also cause the swelling of the hydrogel,which not only provide sufficient space for the growth of ADSCs,but allows the hydrogel to fully fill the irregular defects generated by surgery and residual tumor atrophy,resulting in the on-demand regeneration of adipose tissue.Moreover,the sustained release of AP could be simultaneously triggered along with the size change of hydrogel,which further avoided bacterial infection to promote tissue regeneration.展开更多
Single chemotherapy is difficult to meet the needs of tumor cure. Photothermia combined with chemotherapy is anew and effective anti-tumor therapy. However, the drug loading of nanoparticles and increase in performanc...Single chemotherapy is difficult to meet the needs of tumor cure. Photothermia combined with chemotherapy is anew and effective anti-tumor therapy. However, the drug loading of nanoparticles and increase in performance of photothermalconversion limits the therapeutic effect of combination therapy. In this study, two-dimensional boron (boron, B) nanoparticles wereprepared by ultrasonic exfoliation, and copper sulfide (CuS) nanoparticles and doxorubicin (DOX) were grown on the surface ofthe nanoparticles to form B-CuS-DOX nanoparticles. B-CuS carrier has high DOX drug loading capacity (864mg/g) and goodphotothermal conversion performance (photothermal conversion efficiency at 808nm is 55.8%). At the same time, it can achievedrug release and good photothermal response at near infrared and pH. The nanoparticles designed in this study are expected toprovide an effective chemotherapy-photothermal therapy strategy for tumor therapy in vivo.展开更多
Psoriasis is a prevalent chronic inflammatory skin disorder,characterized by epidermal thickening and an inflammatory hypoxic microenvironment,which significantly hinder drug penetration through the thickened skin and...Psoriasis is a prevalent chronic inflammatory skin disorder,characterized by epidermal thickening and an inflammatory hypoxic microenvironment,which significantly hinder drug penetration through the thickened skin and limit the efficacy of photodynamic therapy(PDT).Here,we introduce a dual-section microneedle(MN)patch(termed S-PTP MN patch)to enhance the therapeutic efficacy of psoriasis treatment.The needle section contains PTP nanoparticles(NPs)loaded with triamcinolone acetonide(TA)and coated with a reactive oxygen species(ROS)-responsive layer,while the base section of the patch encapsulates sodium percarbonate(SPC)particles that serve as oxygen generators to facilitate deep penetration of the PTP NPs into inflammatory sites and improve PDT efficacy.Moreover,the PTP NPs enable sustained release of TA drug over 6 days,demonstrating potent anti-inflammatory activity.In an imiquimod-induced psoriatic mouse model,a single application of the S-PTP MN patch demonstrated superior therapeutic efficacy compared to the conventional topical TA cream,with significantly alleviated clinical symptoms,reduced epidermal thickness,and lowered inflammatory cytokine levels,highlighting the potential of the S-PTP MN patch as a clinically translatable strategy for effective psoriasis therapy.展开更多
Monoclonal antibodies have been used in many diseases,but how to improve their delivery efficiency is still a key issue.As the modification of zwitterionic polymers can maintain the stability and biological activity o...Monoclonal antibodies have been used in many diseases,but how to improve their delivery efficiency is still a key issue.As the modification of zwitterionic polymers can maintain the stability and biological activity of monoclonal antibodies,in this study,zwitterionic monomers,sulfobetaine methacrylate(SBMA),and 3-[[2-(methacryloyloxy)ethyl]dimethylammonio]propionate(CBMA)were used to prepare monoclonal antibody-loaded zwitterionic nanoparticles with the aid of the crosslinker of MMP-2 enzyme-responsive peptide which was a rapid synthesis process under mild conditions.The results from dynamic light scattering(DLS),Fourier transform infrared spectroscopy(FTIR)and transmission electron microscopy(TEM)indicated that a series of zwitterionic nanoparticles had been successfully prepared by the in situ free radical polymerization using the MMP-2 enzyme-responsive peptide as the cross-linking agent.These nanoparticles were spherical with the sizes of(18.7±1.9)nm(SBMA nanoparticle)and(18.2±2.1)nm(CBMA nanoparticle),and the surface contained zwitterionic polymers.It was revealed that they had no cytotoxicity,could be released in tumor microenvironment by enzyme to inhibit the growth of tumor cells,and was able to effectively penetrate endothelial cells(>2%)by transwell.Therefore,the development of this strategy has a great prospect for the delivery of monoclonal antibodies.展开更多
Despite advances in screening and therapeutic strategies,approximately 50%of cancers are diagnosed at advanced stages,and treatment efficacy and disease prognosis remain limited[1,2].Early diagnosis is thus critical f...Despite advances in screening and therapeutic strategies,approximately 50%of cancers are diagnosed at advanced stages,and treatment efficacy and disease prognosis remain limited[1,2].Early diagnosis is thus critical for improving survival.While circulating biomarkers(e.g.,cell-free DNA,tumor proteins,and proteases)provide non-invasive information about tumors,their utilization in early detection is constrained by heterogeneity,rapid degradation,and dilution effects,typically requiring a high tumor burden for reliable detection(Table S1 online)[3,4].Synthetic biomarkers address these limitations by leveraging tumor enzyme-responsive release of engineered reporters,such as fluorophores[5],oligonucleotides[6],or peptides[7].These systems amplify signals in situ and generate quantifiable outputs in biofluids,thereby enhancing sensitivity and specificity beyond those of conventional methods[8].However,although detecting tumors as small as 2.8 mm^(3) is possible in preclinical models[9],the detection at sub-millimeter or cellular levels remains challenging due to inadequate delivery and signal amplification(Table S2 online).展开更多
Neuroinflammation is one of the three important pathological features in neurodegenerative diseases including Parkinson’s disease(PD).The regulation of neuroinflammation can reduce the severity of neurological damage...Neuroinflammation is one of the three important pathological features in neurodegenerative diseases including Parkinson’s disease(PD).The regulation of neuroinflammation can reduce the severity of neurological damage to alleviate diseases.Numerous studies have shown that the phenotype switch of microglia is tightly associated with the nuclear factorκB(NF-κB)-mediated inflammatory pathway.Therefore,the small interfering RNA(siRNA)therapy for downregulating the expression of NF-κB,provides a promising therapeutic strategy for Parkinson’s disease treatments.Considering the brain delivery challenges of siRNA,a sequential targeting inflammation regulation(STIR)delivery system based on poly(amino acid)s is developed to improve the therapeutic effects of Parkinson’s disease treatments.The STIR system sequentially targets the blood–brain barrier and the microglia to enhance the effective concentration of siRNA in the targeted microglia.The results demonstrate that the STIR nanoparticles can transform microglial phenotypes and regulate brain inflammation,thus achieving neuronal recovery and abnormal aggregation ofα-synuclein protein(α-syn)reduction in the treatment of Parkinson’s disease.Herein,this STIR delivery system provides a promising therapeutic platform in PD treatments and has great potential for other neurodegenerative diseases’therapies.展开更多
Due to the special physiological and pathological characteristics of gliomas,most therapeutic drugs are prevented from entering the brain.To improve the poor prognosis of existing therapies,researchers have been conti...Due to the special physiological and pathological characteristics of gliomas,most therapeutic drugs are prevented from entering the brain.To improve the poor prognosis of existing therapies,researchers have been continuously developing non-invasive methods to overcome barriers to gliomas therapy.Although these strategies can be used clinically to overcome the blood-brain barrier(BBB),the accurate delivery of drugs to the glioma lesions cannot be ensured.Nano-drug delivery systems(NDDS)have been widely used for precise drug delivery.In recent years,researchers have gathered their wisdom to overcome barriers,so many well-designed NDDS have performed prominently in preclinical studies.These meticulous designs mainly include cascade passing through BBB and targeting to glioma lesions,drug release in response to the glioma microenvironment,biomimetic delivery systems based on endogenous cells/extracellular vesicles/protein,and carriers created according to the active ingredients of traditional Chinese medicines.We reviewed these well-designed NDDS in detail.Furthermore,we discussed the current ongoing and completed clinical trials of NDDS for gliomas therapy,and analyzed the challenges and trends faced by clinical translation of these well-designed NDDS.展开更多
The dual role of reactive oxygen and nitrogen species(RONS)in physiological and pathological processes in biological systems has been widely reported.It has been recently suggested that the regulation of RONS levels u...The dual role of reactive oxygen and nitrogen species(RONS)in physiological and pathological processes in biological systems has been widely reported.It has been recently suggested that the regulation of RONS levels under physiological and pathological conditions is a potential therapy to promote health and treat diseases,respectively.Injectable hydrogels have been emerging as promising biomaterials for RONS-related biomedical applications owing to their excellent biocompatibility,three-dimensional and extracellular matrix-mimicking structures,tunable properties and easy functionalization.These hydrogels have been developed as advanced injectable platforms for locally generating or scavenging RONS,depending on the specific conditions of the target disease.In this review article,the design principles and mechanism by which RONS are generated/scavenged from hydrogels are outlined alongside a discussion of their in vitro and in vivo evaluations.Additionally,we highlight the advantages and recent developments of these injectable RONS-controlling hydrogels for regenerativemedicines and tissue engineering applications.展开更多
文摘The authors regret the inadvertent error was found in Fig.7 where the merged rows of the images were reversed due to carelessness and negligence.The corrected Fig.7 is presented below.The authors confirm that this correction does not affect the conclusion of the study.
文摘The authors regret the inadvertent error was found in Fig.7 where the merged rows of the images were reversed due to carelessness and negligence.The corrected Fig.7 is presented below.The authors confirm that this correction does not affect the conclusion of the study.
基金supported by the financial assistance from Natural Science Fund Project of Science and Technology Department of Jilin Province (Nos.YDZJ202301ZYTS141,YDZJ202501ZYTS793)。
文摘Hepatic fibrosis is regulated by the synergistic actions of various cells and cytokines,with the activation and proliferation of hepatic stellate cells(HSCs) being considered the central event in this process.To achieve specific targeting of activated hepatic stellate cells(a HSCs) and precise treatment of hepatic fibrosis,this study developed a dual-functional drug delivery system(SIL/c RGD-PEG-PPS PMs) with both targeting and responsive release capabilities.It aims to target the αvβ 3 receptor specifically expressed on the surface of a HSCs using the cyclic peptide c(RGDyk),and to exploit the high reactive oxygen species(ROS) level in the cellular microenvironment to achieve concentrated burst release of drugs at the pathological sites of hepatic fibrosis.Based on multiple assessments,SIL/c RGD-PEG-PPS PMs specifically enhanced the targeted delivery of silybin(SIL) to a HSCs,inhibited the proliferation and migration of a HSCs,and exhibited good biosafety.Additionally,it demonstrated excellent anti-fibrotic activity in fibrotic mice.In summary,this study shows great potential in targeted treatment of hepatic fibrosis and provides a multifunctional tool for advancing the research and therapeutic strategies of hepatic fibrosis.
文摘The applications of supramolecular metal-peptide assemblies as catalyst or catalyst precursor have recent attracted increasing attentions.In this work,a fragment of the amyloid β-peptide,NH_(2)-KLVFF-COOH,was assembled into nanofilms with encapsulated Pd,Pt and Au nanoparticles(NPs)via a one-step room temperature electron induction method.The effects of building block,intermolecular interaction,driving force and side-chain on the assembly were investigated.The assembly mechanism was thereby proposed.The crosslinking of peptide monomers results in mainly random and unordered structures.The obtained metal-peptide assemblies are extremely stable in water at neutral pH for long term.However,the metal NPs are able to be responsively released under basic and reductive conditions.The released NPs show a high activity to catalyze the reduction of 4-nitrophenol.The present studies on assembly mechanism and responsive release will be helpful for the design of organic skeletons and also for the future development of peptide stabilized metallic NPs with applications beyond catalysts.
基金The authors are grateful to the Gazi University Scientific Research Foundation for support of this study.
文摘In this research;the release of 5-Fluorouracil (5-FU) from different ionically crosslinked alginate (Alg) beads was investigated by using Fe3+, Al3+, Zn2+, and Ca2+, ions as crosslinking agent. The prepared beads were characterized by Fourier Transform Infrared Spectroscopy (FTIR) Differential Scanning Calorimetry (DSC) and Scanning Electron Micros-copy (SEM). The drug release studies were carried out at three pH values 1.2, 6.8 and 7.4 respectively each for two hours. The effects of the preparation conditions as crosslinker type, drug/polymer (w/w) ratio, crosslinker concentration and time of exposure to crosslinker on the release of 5-FU were investigated for 6 hours at 37℃. It was observed that 5-FU release from the beads followed the order of Fe > Zn > Al > Ca-Alg and increased with increasing drug/polymer ratio. At the end of 6 hours, the highest 5-FU release was found to be 90% (w/w) for Fe-Alg beads at the drug/polymer ratio of 1/8 (w/w), crosslinker concentration of 0.05 M, exposure time of 10 minutes respectively. The swelling measurements of the beads supported the release results. Release kinetics was described by Fickian and non-Fickian approaches.
基金support from the National Natural Science Foundation of China(No.81703406 and 22077036)the Fundamental Research Funds for the Central Universities of SCUT(No.2020ZYGXZR056)is greatly acknowledged.
文摘Photoactivatable carbon monoxide-releasing molecules(photoCORMs)have provided a unique opportunity for the manipulation of the highly toxic but physiologically relevant CO gas.Here we describe an operationally simple and efficient one-pot solid-phase synthesis strategy for peptides with azopyridine(azpy)side-chains enabled by the on-resin Mills reaction.
基金supported by the Natural Science Foundation of Guangdong Province (No.2023A1515030291)Science and Technology Program of Guangzhou (No.202201011130280065)+1 种基金National Natural Science Foundation of China (No.82172079)Special Fund of Foshan Climbing Peak Plan (No.2020B018)。
文摘Despite the synergy of immune checkpoint blockade(ICB) therapy and photodynamic therapy(PDT) holds great promise as countermeasures against breast cancer, exploring long-term or flexible short-time therapeutic strategies in “cold” tumors remains a great challenge. Here, we present a polyunsaturated fatty acid-doped liposomal hydrogel Lp(DHA)@CP Gel loaded with photosensitizer chlorin e6(Ce6) and programmed death-ligand 1 antibody(αPD-L1) for flexible local photoimmunotherapy with merely singledosed administration. The presence of polyunsaturated fatty acid(docosahexaenoic acid, DHA) doped in particle membrane endows liposomes with flexibly reactive oxygen species(ROS)-responsive release capability, which was attributed to the presence of abundant unsaturated groups. The αPD-L1 was repeatedly induced to in situ release in response to the PDT under photo-exposure. The immunogenic cell death(ICD) effect of PDT evoked “cold” breast tumor to “hot” one, and then assisted the cascade releasedαPD-L1 to synergistically boost the immunotherapy. After a single dose of peritumoral administration of Lp(DHA)@CP Gel, the on-demand treatment can maximize patient compliance and safety by adjusting therapeutic behaviors via a photo on-off switch. This work presents a flexible medication platform,showing promise in improving the objective response rate of ICB therapy and minimizing its systemic toxicity.
基金the National High Level Talents Special Support Plan(X.C.)the“Young Talent Support Plan”of Xi'an Jiaotong University(X.C.)+2 种基金the Natural Science Foundation of Shaanxi Province(No.2022JZ-48 to X.C.)the National Natural Science Foundation of China(No.82272141 to X.C.)the Shaanxi Provincial Key Research and Development Plan Project(No.2023-JC-QN-0260 to X.Q.).
文摘The irregular defects and residual tumor tissue after surgery are challenges for effective breast cancer treatment.Herein,a smart hydrogel with self-adaptable size and dual responsive cargos release was fabricated to treat breast cancer via accurate tumor elimination,on-demand adipose tissue regeneration and effective infection inhibition.The hydrogel consisted of thiol groups ended polyethylene glycol(SH-PEG-SH)and doxorubicin encapsulated mesoporous silica nanocarriers(DOX@MSNs)double crosslinked hyaluronic acid(HA)after loading of antibacterial peptides(AP)and adipose-derived stem cells(ADSCs).A pH-cleavable unsaturated amide bond was pre-introduced between MSNs and HA frame to perform the tumor-specific acidic environment dependent DOX@MSNs release,meanwhile an esterase degradable glyceryl dimethacrylate cap was grafted on MSNs,which contributed to the selective chemotherapy in tumor cells with over-expressed esterase.The bond cleavage between MSNs and HA would also cause the swelling of the hydrogel,which not only provide sufficient space for the growth of ADSCs,but allows the hydrogel to fully fill the irregular defects generated by surgery and residual tumor atrophy,resulting in the on-demand regeneration of adipose tissue.Moreover,the sustained release of AP could be simultaneously triggered along with the size change of hydrogel,which further avoided bacterial infection to promote tissue regeneration.
文摘Single chemotherapy is difficult to meet the needs of tumor cure. Photothermia combined with chemotherapy is anew and effective anti-tumor therapy. However, the drug loading of nanoparticles and increase in performance of photothermalconversion limits the therapeutic effect of combination therapy. In this study, two-dimensional boron (boron, B) nanoparticles wereprepared by ultrasonic exfoliation, and copper sulfide (CuS) nanoparticles and doxorubicin (DOX) were grown on the surface ofthe nanoparticles to form B-CuS-DOX nanoparticles. B-CuS carrier has high DOX drug loading capacity (864mg/g) and goodphotothermal conversion performance (photothermal conversion efficiency at 808nm is 55.8%). At the same time, it can achievedrug release and good photothermal response at near infrared and pH. The nanoparticles designed in this study are expected toprovide an effective chemotherapy-photothermal therapy strategy for tumor therapy in vivo.
基金supported by the National Natural Science Foundation of China(NSFC,Nos.82373798 and 52103182).
文摘Psoriasis is a prevalent chronic inflammatory skin disorder,characterized by epidermal thickening and an inflammatory hypoxic microenvironment,which significantly hinder drug penetration through the thickened skin and limit the efficacy of photodynamic therapy(PDT).Here,we introduce a dual-section microneedle(MN)patch(termed S-PTP MN patch)to enhance the therapeutic efficacy of psoriasis treatment.The needle section contains PTP nanoparticles(NPs)loaded with triamcinolone acetonide(TA)and coated with a reactive oxygen species(ROS)-responsive layer,while the base section of the patch encapsulates sodium percarbonate(SPC)particles that serve as oxygen generators to facilitate deep penetration of the PTP NPs into inflammatory sites and improve PDT efficacy.Moreover,the PTP NPs enable sustained release of TA drug over 6 days,demonstrating potent anti-inflammatory activity.In an imiquimod-induced psoriatic mouse model,a single application of the S-PTP MN patch demonstrated superior therapeutic efficacy compared to the conventional topical TA cream,with significantly alleviated clinical symptoms,reduced epidermal thickness,and lowered inflammatory cytokine levels,highlighting the potential of the S-PTP MN patch as a clinically translatable strategy for effective psoriasis therapy.
基金the National Natural Science Foundation of China(Grant No.51773151)the Tianjin Applied Basic Research Multi-Input Fund(21JCYBJC01560).
文摘Monoclonal antibodies have been used in many diseases,but how to improve their delivery efficiency is still a key issue.As the modification of zwitterionic polymers can maintain the stability and biological activity of monoclonal antibodies,in this study,zwitterionic monomers,sulfobetaine methacrylate(SBMA),and 3-[[2-(methacryloyloxy)ethyl]dimethylammonio]propionate(CBMA)were used to prepare monoclonal antibody-loaded zwitterionic nanoparticles with the aid of the crosslinker of MMP-2 enzyme-responsive peptide which was a rapid synthesis process under mild conditions.The results from dynamic light scattering(DLS),Fourier transform infrared spectroscopy(FTIR)and transmission electron microscopy(TEM)indicated that a series of zwitterionic nanoparticles had been successfully prepared by the in situ free radical polymerization using the MMP-2 enzyme-responsive peptide as the cross-linking agent.These nanoparticles were spherical with the sizes of(18.7±1.9)nm(SBMA nanoparticle)and(18.2±2.1)nm(CBMA nanoparticle),and the surface contained zwitterionic polymers.It was revealed that they had no cytotoxicity,could be released in tumor microenvironment by enzyme to inhibit the growth of tumor cells,and was able to effectively penetrate endothelial cells(>2%)by transwell.Therefore,the development of this strategy has a great prospect for the delivery of monoclonal antibodies.
基金supported by the National Science Fund for Distinguished Young Scholars(22025406)the National Natural Science Foundation of China(22204162)the Natural Science Foundation of Tianjin City(24JCYBJC01810).
文摘Despite advances in screening and therapeutic strategies,approximately 50%of cancers are diagnosed at advanced stages,and treatment efficacy and disease prognosis remain limited[1,2].Early diagnosis is thus critical for improving survival.While circulating biomarkers(e.g.,cell-free DNA,tumor proteins,and proteases)provide non-invasive information about tumors,their utilization in early detection is constrained by heterogeneity,rapid degradation,and dilution effects,typically requiring a high tumor burden for reliable detection(Table S1 online)[3,4].Synthetic biomarkers address these limitations by leveraging tumor enzyme-responsive release of engineered reporters,such as fluorophores[5],oligonucleotides[6],or peptides[7].These systems amplify signals in situ and generate quantifiable outputs in biofluids,thereby enhancing sensitivity and specificity beyond those of conventional methods[8].However,although detecting tumors as small as 2.8 mm^(3) is possible in preclinical models[9],the detection at sub-millimeter or cellular levels remains challenging due to inadequate delivery and signal amplification(Table S2 online).
基金the National Natural Science Foundation of China(Nos:22075289,21875254,31771095,and 52073287).
文摘Neuroinflammation is one of the three important pathological features in neurodegenerative diseases including Parkinson’s disease(PD).The regulation of neuroinflammation can reduce the severity of neurological damage to alleviate diseases.Numerous studies have shown that the phenotype switch of microglia is tightly associated with the nuclear factorκB(NF-κB)-mediated inflammatory pathway.Therefore,the small interfering RNA(siRNA)therapy for downregulating the expression of NF-κB,provides a promising therapeutic strategy for Parkinson’s disease treatments.Considering the brain delivery challenges of siRNA,a sequential targeting inflammation regulation(STIR)delivery system based on poly(amino acid)s is developed to improve the therapeutic effects of Parkinson’s disease treatments.The STIR system sequentially targets the blood–brain barrier and the microglia to enhance the effective concentration of siRNA in the targeted microglia.The results demonstrate that the STIR nanoparticles can transform microglial phenotypes and regulate brain inflammation,thus achieving neuronal recovery and abnormal aggregation ofα-synuclein protein(α-syn)reduction in the treatment of Parkinson’s disease.Herein,this STIR delivery system provides a promising therapeutic platform in PD treatments and has great potential for other neurodegenerative diseases’therapies.
基金financial support from National Natural Science Foundation of China(Nos.81903557 and 82074024)Natural Science Foundation of Jiangsu Province(No.BK20190802,China)+3 种基金Natural Science Foundation Youth Project of Nanjing University of Chinese Medicine(No.NZY81903557,China)the Open Project of Chinese Materia Medica First-Class Discipline of Nanjing University of Chinese Medicine(No.2020YLXK019,China)the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(No.19KJB350003,China)College Students’Innovative Entrepreneurial Training Plan Program of Nanjing University of Chinese Medicine(No.202010315XJ040,China)。
文摘Due to the special physiological and pathological characteristics of gliomas,most therapeutic drugs are prevented from entering the brain.To improve the poor prognosis of existing therapies,researchers have been continuously developing non-invasive methods to overcome barriers to gliomas therapy.Although these strategies can be used clinically to overcome the blood-brain barrier(BBB),the accurate delivery of drugs to the glioma lesions cannot be ensured.Nano-drug delivery systems(NDDS)have been widely used for precise drug delivery.In recent years,researchers have gathered their wisdom to overcome barriers,so many well-designed NDDS have performed prominently in preclinical studies.These meticulous designs mainly include cascade passing through BBB and targeting to glioma lesions,drug release in response to the glioma microenvironment,biomimetic delivery systems based on endogenous cells/extracellular vesicles/protein,and carriers created according to the active ingredients of traditional Chinese medicines.We reviewed these well-designed NDDS in detail.Furthermore,we discussed the current ongoing and completed clinical trials of NDDS for gliomas therapy,and analyzed the challenges and trends faced by clinical translation of these well-designed NDDS.
基金supported by a grant from Priority Research Centers Program(2019R1A6A1A11051471)funded by the National Research Foundation of Korea(NRF)and Korea Medical Device Development Fund grant funded by the Korea government(the Ministry of Science and ICT,the Ministry of Trade,Industry and Energy,the Ministry of Health&Welfare and the Ministry of Food and Drug Safety)(Project Number:RS-2020-KD000033)Korea Evaluation Institute of Industrial Technology(KEIT 20018560,NTIS 1415180625)funded by the Ministry of Trade,Industry&Energy(MOTIE,Korea).
文摘The dual role of reactive oxygen and nitrogen species(RONS)in physiological and pathological processes in biological systems has been widely reported.It has been recently suggested that the regulation of RONS levels under physiological and pathological conditions is a potential therapy to promote health and treat diseases,respectively.Injectable hydrogels have been emerging as promising biomaterials for RONS-related biomedical applications owing to their excellent biocompatibility,three-dimensional and extracellular matrix-mimicking structures,tunable properties and easy functionalization.These hydrogels have been developed as advanced injectable platforms for locally generating or scavenging RONS,depending on the specific conditions of the target disease.In this review article,the design principles and mechanism by which RONS are generated/scavenged from hydrogels are outlined alongside a discussion of their in vitro and in vivo evaluations.Additionally,we highlight the advantages and recent developments of these injectable RONS-controlling hydrogels for regenerativemedicines and tissue engineering applications.
