Mesoporous silica nanoparticles(MsNs)are thought to be an attractive drug delivery material because of their advantages including high specific surface area,tunable pore size and morphology,easy sur-face modification ...Mesoporous silica nanoparticles(MsNs)are thought to be an attractive drug delivery material because of their advantages including high specific surface area,tunable pore size and morphology,easy sur-face modification and good biocompatibility.However,as a result of the poor biodegradability of MsNs,their biomedical applications are limited.To break the bottleneck of limited biomedical applications of MSNs,more and more researchers tend to design biodegradable MSNs(b-MSNs)nanosystems to obtain biodegradable as well as safe and reliable drug delivery carriers.In this review,we focused on sum-marizing strategies to improve the degradability of MsNs and innovatively proposed a series of advan-tages of b-MsNs,including controlled cargo release behavior,multifunctional frameworks,nano-catalysis,bio-imaging capabilities and enhanced therapeutic effects.Based on these advantages,we have inno-vatively summarized the applications of b-MsNs for enhanced tumor theranostics,including enhanced chemotherapy,delivery of nanosensitizers,gas molecules and biomacromolecules,initiation of immune response,synergistic therapies and image-guided tumor diagnostics.Finally,the challenges and further clinical translation potential of nanosystems based on b-MsNs are fully discussed and prospected.We believe that such b-MsNs delivery carriers will provide a timely reference for further applications in tu-mor theranostics.展开更多
As the third essential trace element in the human body,copper plays a crucial role in various physiological processes,which lays the foundation for its broad applications in cancer treatments.The overview of copper,in...As the third essential trace element in the human body,copper plays a crucial role in various physiological processes,which lays the foundation for its broad applications in cancer treatments.The overview of copper,including pharmacokinetics,signaling pathways,and homeostasis dysregulation,is hereby discussed.Additionally,cuproptosis,as a newly proposed cell death mechanism associated with copper accumulation,is analyzed and further developed for efficient cancer treatment.Different forms of Cu-based nanoparticles and their advantages,aswell as limiting factors,are introduced.Moreover,the unique characteristics of Cu-based nanoparticles give rise to their applications in various imaging modalities.In addition,Cu-based nanomaterials are featured by their excellent photothermal property and ROS-associated tumor-killing potential,which are widely explored in diverse cancer therapies and combined therapies.Reducing the concentration of Cu^(2+)/Cu^(+)is another cancer-killing method,and chelators can meet this need.More importantly,challenges and future prospects are identified for further research.展开更多
Particle size and surface properties are crucial for lymphatic drainage(LN),dendritic cell(DC)uptake,DC maturation,and antigen cross-presentation induced by nanovaccine injection,which lead to an effective cell-mediat...Particle size and surface properties are crucial for lymphatic drainage(LN),dendritic cell(DC)uptake,DC maturation,and antigen cross-presentation induced by nanovaccine injection,which lead to an effective cell-mediated immune response.However,the manner in which the particle size and surface properties of vaccine carriers such as mesoporous silica nanoparticles(MSNs)affect this immune response is unknown.We prepared 50,100,and 200 nm of MSNs that adsorbed ovalbumin antigen(OVA)while modifyingβ-glucan to enhance immunogenicity.The results revealed that these MSNs with different particle sizes were just as efficient in vitro,and MSNs withβ-glucan modification demonstrated higher efficacy.However,the in vivo results indicated that MSNs with smaller particle sizes have stronger lymphatic targeting efficiency and a greater ability to promote the maturation of DCs.The results also indicate thatβ-glucan-modified MSN,with a particle size of∼100 nm,has a great potential as a vaccine delivery vehicle and immune adjuvant and offers a novel approach for the delivery of multiple therapeutic agents that target other lymph-mediated diseases.展开更多
The objective of this work is to construct a nanosuspension drug delivery system of probucol,a BCS II drug,in order to improve its dissolution and oral bioavailability.The wet milling procedure using planetary beads-m...The objective of this work is to construct a nanosuspension drug delivery system of probucol,a BCS II drug,in order to improve its dissolution and oral bioavailability.The wet milling procedure using planetary beads-milling equipment was utilized to grind the raw probucol to ultrafine nanoparticle/nanocrystal aqueous suspension that was further solidified by freeze-drying process.Cellulose derivatives of different substitution groups and molecular weights,including HPMC,HPC,and MC,were evaluated as the primary stabilizer of probucol nanosuspension.Ternary stabilizers system composed of a primary stabilizer(cellulose derivative,i.e.HPC),a nonionic surfactant(Pluronic R F68),and an anionic surfactant(SDS)was employed to obtain probucol nanosuspension of finer particle size and enhanced dissolution in aqueous media.The probucol nanosuspension with good physical stability showed no obvious change of particle size even after storing over 7 d at 4°C or 25°C.The solidified probucol nanosuspension with trehalose as the cryoprotectant showed the highest dissolution rate(>60%at 2 h)compared to other cryoprotectant.The in vivo pharmacokinetic evaluation indicated about 15-folds higher AUC value of the probucol nanosuspension compared to that of coarse probucol suspension after oral administration to rats.The probucol nanosuspension prepared by wet-milling and ternary stabilizers system may find wide applications for improving the dissolution and oral absorption of water-insoluble drugs.展开更多
To improve the corneal permeability and water-solubility of disulfiram(DSF), which is an ocular drug for cataract, P188 was selected as a matrix to prepare solid dispersion of DSF(DSF SD) by hot melt method. The DSF S...To improve the corneal permeability and water-solubility of disulfiram(DSF), which is an ocular drug for cataract, P188 was selected as a matrix to prepare solid dispersion of DSF(DSF SD) by hot melt method. The DSF SD was characterized by DSC, XRD, and IR, and the results suggested that DSF was amorphous in DSF SD. The DSF SD was added to borate buffer solution(BBS) contained 20% poloxamer P407 and 1.2% poloxamer P188 to form in-situ gel. In vitro and in vivo experiments revealed that DSF SD combined with in-situ gel(DSF SD/in-situ gel) increased the residence time and the amount of DSF penetrated through the corneal. The pharmacodynamics studies exhibited DSF SD/in-situ gel delayed the development of selenium-induced cataract at some content. These results investigated that DSF SD/in-situ gel as a drug delivery system can improve DSF ocular permeability.展开更多
In this study,a polymeric lipid nanoparticle(NP)(simplified as Lipid NP)was reported as a promising oral vaccine delivery system.The Lipid NPs composed of a hydrophobic polymeric poly(D,L-lactide-co-glycolide)(PLGA)co...In this study,a polymeric lipid nanoparticle(NP)(simplified as Lipid NP)was reported as a promising oral vaccine delivery system.The Lipid NPs composed of a hydrophobic polymeric poly(D,L-lactide-co-glycolide)(PLGA)core and a surface coating of lipid monolayer.Membrane emulsification technique was used to obtain uniform-sized Lipid NPs.Ovalbumin(OVA)was used as a model vaccine.Compared with the pure PLGA NPs,the Lipid NPs achieved higher loading capacity(LC)and entrapment efficiency(EE)for the encapsulated OVA.An in vitro oral release profile showed that the OVA-Lipid NPs were with lower initial burst and could protect the loaded OVA from the harsh gastrointestinal(GI)environment for a long time.In addition,a human microfold cell(M-cell)transcytotic assay demonstrated that due to a lipid layer structure on the particle surface,the Lipid NPs showed higher affinity to the M-cells.Since the M-cell in the intestinal epithelium played an important role in particle transportation as well as intimately associated with the underlying immune cells,the OVA-Lipid NPs effectively induced mucosal and humoral immune responses.展开更多
We applied a combination of inorganic mesoporous silica material,frequently used as drug carriers,and a natural organic polymer alginate(ALG),to establish a sustained drug delivery system for the poorly water-soluble ...We applied a combination of inorganic mesoporous silica material,frequently used as drug carriers,and a natural organic polymer alginate(ALG),to establish a sustained drug delivery system for the poorly water-soluble drug Indomethacin(IND).Mesoporous silica nanospheres(MSNs)were synthesized using an organic template method and then functionalized with aminopropyl groups through postsynthesis.After drug loading into the pores of aninopropyl functionalized MSNs(AP-MSNs),IND loaded AP-MSNs(IND-AP-MSNs)were encapsulated by ALG through the ionic interaction.The effects of surface chemical groups and ALG layer on IND release were systematically studied using scanning electron microscopy(SEM),transmission electron microscopy(TEM),nitrogen adsorption,zetapotential analysis and TGA analysis.The surface structure and surface charge changes of the ALG encapsulated AP-MSNs(ALG-AP-MSNs)were also investigated.The results showed that sustained release of IND from the designed drug delivery system was mainly due to the blockage effect from the coated ALG.We believe that this combination will help designing oral sustained drug delivery systems for poorly water-soluble drugs.展开更多
To achieve GSH-responsive 5-Fluorouridine(5-FU) delivery, a novel family of nanogel drug carriers has been successfully prepared. The new class of PAHy-based nanogels was prepared by the crossing-link reaction of poly...To achieve GSH-responsive 5-Fluorouridine(5-FU) delivery, a novel family of nanogel drug carriers has been successfully prepared. The new class of PAHy-based nanogels was prepared by the crossing-link reaction of poly-α, β-polyasparthydrazide(PAHy) chains and 3,3′-dithiodipropionic acid(DTDPA) consisting of a redox-responsive chain network. This particle highlights recent efforts in introducing a disulfide bond to drug delivery nanogel by DTDPA,and the increased release properties of complex nanogels produced excellent glutathione(GSH)-sensitivity and significant anti-tumor therapeutic efficacy. The PAHy-based nanogels were characterized by Fourier transform infrared spectroscopy(FT-IR), dynamic light scattering(DLS)(nano-particle size ~200 nm), UV–vis spectrometry, X-ray diffraction(XRD) and differential scanning calorimetric(DSC). PAHy-based nanogels are promising controlledrelease carriers for the tumor-targeting delivery of the anticancer agent 5-Fluorouridine.展开更多
In the current study,mesoporous carbon(MC)with pore volume(1.53 cm3/g)and pore size(9.74 nm)was successfully prepared as a carrier for celecoxib(CEL).Celecoxib was loaded into the pore channels of MC using three diffe...In the current study,mesoporous carbon(MC)with pore volume(1.53 cm3/g)and pore size(9.74 nm)was successfully prepared as a carrier for celecoxib(CEL).Celecoxib was loaded into the pore channels of MC using three different methods:solvent evaporation method,absorption method and physical mixing method.Solid-state characterization methods,such as SEM,TEM,BET,DSC and XRD were used to systematically investigate the process of the drug loading system.Dissolution tests were performed to examine the effects of MC on the release of CEL.Furthermore,the cytotoxicity,wound healing,migration and invasion experiments were carried out to measure the contribution of MC to the anti-tumor metastasis ability of celecoxib on MDA-MB-231 cells.The results showed that CEL could be kept in a non-crystalline state when they were incorporated into the MC using the solvent evaporation method or absorption method.The dissolution rate of CEL released from MCS(Mesoporous carbon e Celecoxib e Solvent evaporation method)and MCA(Mesoporous carbon e Celecoxib e Absorption evaporation method)was all significantly higher than that of pure CEL.The cumulative release for MCS within the 5 min was up to 51.86%.MCS enhanced the inhibitory effect of CEL on the migration and invasion of MDAMB-231 cells.展开更多
Mesoporous silica cocoon materials(MSNCs) and MgO doped mesoporous silica cocoons(MgO-MSNCs) with the cocoon-like hierarchical morphology and different alkalinities were synthesized as carriers for acidic drugs. Indom...Mesoporous silica cocoon materials(MSNCs) and MgO doped mesoporous silica cocoons(MgO-MSNCs) with the cocoon-like hierarchical morphology and different alkalinities were synthesized as carriers for acidic drugs. Indomethacin(IMC) was selected as a model drug and loaded into carriers. All materials and the drug-loaded samples were characterized by nitrogen adsorption, FTIR spectroscopy, transmission electron microscopy(TEM), powder X-Ray diffraction(XRD) and differential scanning calorimetry(DSC). The effect of the Mg/Si molar ratio on the kinetics and equilibrium of IMC adsorption on MgO-MSNCs was thoroughly examined, and it was found that the increase in the Mg/Si molar ratio resulted in an increasing IMC adsorption rate due to the increased affinity between alkaline MgO-MSNCs and weak acid IMC. The adsorption kinetics fitted a pseudo second-order model well. The Freundlich isotherm showed a better fit, indicating that the coverage of IMC on the surface of MgO-MSNCs was heterogeneous. The maximum adsorption capacity of adsorbent was calculated by the Langmuir isotherm equation. The Temkin equation provided further support that the IMC adsorption on MgO-MSNCs was dominated by a chemisorption process. MgO-MSNCs also have the advantage of allowing an adjustment of the drug release rate of weak acid drug. The cytotoxicity assay indicated good biocompatibility of MgO-MSNCs. Our research on MgO-MSNCs carriers demonstrated their potential therapeutic benefit for safe and effective management of IMC adsorption and in vitro release.展开更多
In this study,phosphonate-terminated magnetic mesoporous nanoparticles(pMMSNs)was designed by incorporation of MNPs in the center of mesoporous silica nanoparticles(MSNs)and followed by grafting phosphonate group on t...In this study,phosphonate-terminated magnetic mesoporous nanoparticles(pMMSNs)was designed by incorporation of MNPs in the center of mesoporous silica nanoparticles(MSNs)and followed by grafting phosphonate group on to the surface of MMSNs.The carrier exhibited a typical superparamagnetic feature and the saturation magnetization was 4.89 emu/g measured by vibrating sample magnetometer(VSM).pMMSNs had a spherical morphology and a pore size of 2.2 nm.FromN2 adsorption-desorption analysis,pMMSNs had a surface area of 613.4 m^(2)/g and a pore volume of 0.78 cm^(3)/g.Phosphonate modification improved the colloidal stability of MMSNs,and the hydrodynamic diameter of pMMSNs was around 175 nm.The hydrophilic phosphonate group significantly enhanced the negative surface charge of MMSNs from -19.3 mV to -28.8 mV pMMSNs with more negative surface charge had a 2.3-fold higher drug loading capacity than that of MMSNs.In addition,the rate and amount of release of doxorubicin(DOX)from DOX/pMMSNs was pH-dependent and increased with the decrease of pH.At pH 7.4,the release amount was quite low and only approximately 17wt%ofDOXwasreleasedin48h.AtpH5.0and3.0,the release rate increased significantly and the release amount achieved 31 wt%and 60 wt%in 48 h,respectively.To evaluate the magnetic targeting performance ofpMMSNs,FITC labeledpMMSNswas injected into mice bearing S180 solid tumor.FITC labeledpMMSNscontrolled by an external magnetic field showed higher tumor accumulation and lower normal tissue distribution.展开更多
The purpose of this study was to develop poly(amidoamine)(PAMAM)-functionalized multi-walled carbon nanotubes(MWNTs)loaded with a poorly water-soluble drug,intended to improve the drug-loading capacity,dissolution an...The purpose of this study was to develop poly(amidoamine)(PAMAM)-functionalized multi-walled carbon nanotubes(MWNTs)loaded with a poorly water-soluble drug,intended to improve the drug-loading capacity,dissolution and design a sustained release system.MWNTs were modified with a carboxyl group by acid treatment and then complex with PAMAM.PAMAM-MWNTs were investigated as a scaffold for loading the model drug,Carvedilol(CAR),using three different methods(the fusion method,the incipient wetness impregnation method,and the solvent method).The effects of different pore size,specific surface area and physical state were systematically studied using FT-IR,TGA,SEM,DSC,nitrogen adsorption,XPS and XRD.All the samples made by PAMAM-MWNTs to load the drug had a marked effect on the drug-loading capacity as well as drug dissolution,especially theⅡ-30%.展开更多
Dear Editors,Bispecific antibodies(bsAbs),which possess the unique ability to bind to two different antigens simultaneously(Labrijn et al.,2019),have emerged as powerful tools in the field of cancer immunotherapy and ...Dear Editors,Bispecific antibodies(bsAbs),which possess the unique ability to bind to two different antigens simultaneously(Labrijn et al.,2019),have emerged as powerful tools in the field of cancer immunotherapy and pathogen prevention.Their design and production are of great significance,as they can enhance the effectiveness of targeted therapy by improving the accuracy and efficiency of attacks against multiple targets.However,compared with traditional monoclonal antibodies,the design and production of bsAbs are more complex.One major challenge facing the conventional IgG bispecific format is the efficient pairing of different chains,known as the chain association issue.To overcome this,researchers have sought to promote heavychain heterodimerization through Fc engineering techniques,such as knobs-intoholes(KiH)and controlled Fab arm exchange.Others have highlighted the benefit of simple heavy-light chain paired formats,as they completely bypass the chain association issue while offering improved manufacturability.展开更多
Reactive oxygen species(ROS)generated from photosensitizers exhibit great potential for repolarizing immunosuppressive tumor-associated macrophages(TAMs)toward the anti-tumor M1 phenotype,representing a promising canc...Reactive oxygen species(ROS)generated from photosensitizers exhibit great potential for repolarizing immunosuppressive tumor-associated macrophages(TAMs)toward the anti-tumor M1 phenotype,representing a promising cancer immunotherapy strategy.Nevertheless,their effectiveness in eliminating solid tumors is generally limited by the instability and inadequate TAMs-specific targeting of photosensitizers.Here,a novel core-shell integrated nano platform is proposed to achieve a coordinated strategy of repolarizing TAMs for potentiating cancer immunotherapy.Colloidal mesoporous silica nanoparticles(CMSN)are fabricated to encapsulate photosensitizer-Indocyanine Green(ICG)to improve their stability.Then ginseng-derived exosome(GsE)was coated on the surface of ICG/CMSN for targeting TAMs,as well as repolarizing TAMs concurrently,named ICG/CMSN@GsE.As expected,with the synergism of ICG and GsE,ICG/CMSN@GsE exhibited better stability,mild generation of ROS,favorable specificity toward M2-like macrophages,enhancing drug retention in tumors and superior TAMs repolarization potency,then exerted a potent antitumor effect.In vivo,experiment results also confirm the synergistic suppression of tumor growth accompanied by the increased presence of anti-tumor M1-like macrophages and maximal tumor damage.Taken together,by integrating the superiorities of TAMs targeting specificity and synergistic TAMs repolarization effect into a single nanoplatform,ICG/CMSN@GsE can readily serve as a safe and high-performance nanoplatform for enhanced cancer immunotherapy.展开更多
The authors regret that there is an error in the article Fig.9D1 due to the mistake of copying and pasting in the process of assembling figures and negligence in the proofreading,and also a mislabled error in the supp...The authors regret that there is an error in the article Fig.9D1 due to the mistake of copying and pasting in the process of assembling figures and negligence in the proofreading,and also a mislabled error in the supporting Information Fig.S9 and S10.展开更多
The limited penetration of nanoparticles and their poor accessibility to cancer cell fractions in tumor remain essential challenges for effective anticancer therapy.Herein,we designed a targeting peptide-decorated bio...The limited penetration of nanoparticles and their poor accessibility to cancer cell fractions in tumor remain essential challenges for effective anticancer therapy.Herein,we designed a targeting peptide-decorated biomimetic lipoprotein(termed as BL-RD)to enable their deep penetration and efficient accessibility to cancer cell fractions in a tumor,thereby improving the combinational chemophotodynamic therapy of triple negative breast cancer.BL-RD was composed of phospholipids,apolipoprotein A1 mimetic peptide(PK22),targeting peptide-conjugated cytotoxic mertansine(RM)and photodynamic agents of DiIC18(5)(DiD).The counterpart biomimetic lipoprotein system without RM(termed as BL-D)was fabricated as control.Both BL-D and BL-RD were nanometer-sized particles with a mean diameter of less than 30 nm and could be efficiently internalized by cancer cells.After intravenous injection,they can be specifically accumulated at tumor sites.When comparing to the counterpart BLD,BL-RD displayed superior capability to permeate across the tumor mass,extravasate from tumor vasculature to distant regions and efficiently access the cancer cell fractions in a solid tumor,thus producing noticeable depression of the tumor growth.Taken together,BL-RD can be a promising delivery nanoplatform with prominent tumor-penetrating and cancer cells-accessing capability for effective tumor therapy.展开更多
Utilization of the intestinal lymphatic pathway will allow extraordinary gains in lymph and tumors cascade-targeted delivery of oral drugs and awakening the innate/adaptive immunity of the body and the lesion microenv...Utilization of the intestinal lymphatic pathway will allow extraordinary gains in lymph and tumors cascade-targeted delivery of oral drugs and awakening the innate/adaptive immunity of the body and the lesion microenvironment,in addition to improving oral bioavailability relative to other means of delivery of oral drugs.Here,inspired by the specific invasion route of intestinal microorganisms,we pioneered an immune-awakening Saccharomyces-inspired mesoporous silicon nanoparticle(yMSN)for the ingenious cascade-targeted delivery of therapeutic cancer vaccines and antitumor drugs to lymph and tumors via the intestinal lymphatic pathway.Encouragingly,yMSN high-loaded tumor-specific antigens(OVA,11.9%)and anti-tumor drugs(Len,28.6%)with high stability,namely Len/OVA/yMSN,efficiently co-delivered OVA and Len to their desired target sites.Moreover,yMSN concomitantly awakened the innate antitumor immunity of dendritic cells and macrophages,strengthening vaccine-induced adaptive immune responses and reversing macrophage-associated immunosuppression in the tumor microenvironment.Surprisingly,Len/OVA/yMSN treatment resulted in excellent synergistic antitumor efficacy and long-term antitumor memory in OVA-Hepa1-6-bearing mice.This high-performance nanocarrier provides a novel approach for lesion-targeting delivery of oral drugs accompanied with awakening of the innate/adaptive immunity of the lesion environment,and also represents a novel path for the oral delivery of diverse therapeutic agents targeting other lymph-mediated diseases.展开更多
Dear Editor As of January 2023,coronavirus disease 2019(COVID-19)induced by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused more than 6.7 million deaths,with SARS-CoV-2 variants continuing to alt...Dear Editor As of January 2023,coronavirus disease 2019(COVID-19)induced by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused more than 6.7 million deaths,with SARS-CoV-2 variants continuing to alter the trajectory of the COVID-19 pandemic.Indeed,the prevalence of the newly emergent Omicron sublineages,particularly BA.4/5 and XBB,has highlighted the critical need for the design and production of broadly potent neutralization antibodies to efficiently combat SARS-CoV-2 variants.Neutralizing antibodies(nAbs)XMA01,XMA04,and XMA09,which target noncompeting antigenic sites in RBD(receptor binding domain),exhibit high neutralization potency against earlier disease variants(Supplementary Fig.1a–d),as previously reported by us.展开更多
基金from"XingLiao Talent Program"of Liaoning Province(No.XLYC2203156)Shenyang Young and Middle-aged Science and Technology Innovation Talent Support Program(No.RC220397)are greatly acknowledged。
文摘Mesoporous silica nanoparticles(MsNs)are thought to be an attractive drug delivery material because of their advantages including high specific surface area,tunable pore size and morphology,easy sur-face modification and good biocompatibility.However,as a result of the poor biodegradability of MsNs,their biomedical applications are limited.To break the bottleneck of limited biomedical applications of MSNs,more and more researchers tend to design biodegradable MSNs(b-MSNs)nanosystems to obtain biodegradable as well as safe and reliable drug delivery carriers.In this review,we focused on sum-marizing strategies to improve the degradability of MsNs and innovatively proposed a series of advan-tages of b-MsNs,including controlled cargo release behavior,multifunctional frameworks,nano-catalysis,bio-imaging capabilities and enhanced therapeutic effects.Based on these advantages,we have inno-vatively summarized the applications of b-MsNs for enhanced tumor theranostics,including enhanced chemotherapy,delivery of nanosensitizers,gas molecules and biomacromolecules,initiation of immune response,synergistic therapies and image-guided tumor diagnostics.Finally,the challenges and further clinical translation potential of nanosystems based on b-MsNs are fully discussed and prospected.We believe that such b-MsNs delivery carriers will provide a timely reference for further applications in tu-mor theranostics.
基金Grant from Liaoning Provincal National Nature Science Foundation of China(No.2023-MS-202)is greatly acknowledged.
文摘As the third essential trace element in the human body,copper plays a crucial role in various physiological processes,which lays the foundation for its broad applications in cancer treatments.The overview of copper,including pharmacokinetics,signaling pathways,and homeostasis dysregulation,is hereby discussed.Additionally,cuproptosis,as a newly proposed cell death mechanism associated with copper accumulation,is analyzed and further developed for efficient cancer treatment.Different forms of Cu-based nanoparticles and their advantages,aswell as limiting factors,are introduced.Moreover,the unique characteristics of Cu-based nanoparticles give rise to their applications in various imaging modalities.In addition,Cu-based nanomaterials are featured by their excellent photothermal property and ROS-associated tumor-killing potential,which are widely explored in diverse cancer therapies and combined therapies.Reducing the concentration of Cu^(2+)/Cu^(+)is another cancer-killing method,and chelators can meet this need.More importantly,challenges and future prospects are identified for further research.
基金supported by the Doctoral Start-up Foundation of Liaoning Province,China(Grant No.:2021-BS-127)China Medical University,China Medical University Cancer Hospital in animal experiments.
文摘Particle size and surface properties are crucial for lymphatic drainage(LN),dendritic cell(DC)uptake,DC maturation,and antigen cross-presentation induced by nanovaccine injection,which lead to an effective cell-mediated immune response.However,the manner in which the particle size and surface properties of vaccine carriers such as mesoporous silica nanoparticles(MSNs)affect this immune response is unknown.We prepared 50,100,and 200 nm of MSNs that adsorbed ovalbumin antigen(OVA)while modifyingβ-glucan to enhance immunogenicity.The results revealed that these MSNs with different particle sizes were just as efficient in vitro,and MSNs withβ-glucan modification demonstrated higher efficacy.However,the in vivo results indicated that MSNs with smaller particle sizes have stronger lymphatic targeting efficiency and a greater ability to promote the maturation of DCs.The results also indicate thatβ-glucan-modified MSN,with a particle size of∼100 nm,has a great potential as a vaccine delivery vehicle and immune adjuvant and offers a novel approach for the delivery of multiple therapeutic agents that target other lymph-mediated diseases.
基金financial support from the National Basic Research Program of China(973 Program,No.2009CB930300)
文摘The objective of this work is to construct a nanosuspension drug delivery system of probucol,a BCS II drug,in order to improve its dissolution and oral bioavailability.The wet milling procedure using planetary beads-milling equipment was utilized to grind the raw probucol to ultrafine nanoparticle/nanocrystal aqueous suspension that was further solidified by freeze-drying process.Cellulose derivatives of different substitution groups and molecular weights,including HPMC,HPC,and MC,were evaluated as the primary stabilizer of probucol nanosuspension.Ternary stabilizers system composed of a primary stabilizer(cellulose derivative,i.e.HPC),a nonionic surfactant(Pluronic R F68),and an anionic surfactant(SDS)was employed to obtain probucol nanosuspension of finer particle size and enhanced dissolution in aqueous media.The probucol nanosuspension with good physical stability showed no obvious change of particle size even after storing over 7 d at 4°C or 25°C.The solidified probucol nanosuspension with trehalose as the cryoprotectant showed the highest dissolution rate(>60%at 2 h)compared to other cryoprotectant.The in vivo pharmacokinetic evaluation indicated about 15-folds higher AUC value of the probucol nanosuspension compared to that of coarse probucol suspension after oral administration to rats.The probucol nanosuspension prepared by wet-milling and ternary stabilizers system may find wide applications for improving the dissolution and oral absorption of water-insoluble drugs.
基金supported by Liaoning Provincial Key Labora-tory of Drug Preparation Design and Evaluation of Liaoning Provincial Education Department(LZ2014045)
文摘To improve the corneal permeability and water-solubility of disulfiram(DSF), which is an ocular drug for cataract, P188 was selected as a matrix to prepare solid dispersion of DSF(DSF SD) by hot melt method. The DSF SD was characterized by DSC, XRD, and IR, and the results suggested that DSF was amorphous in DSF SD. The DSF SD was added to borate buffer solution(BBS) contained 20% poloxamer P407 and 1.2% poloxamer P188 to form in-situ gel. In vitro and in vivo experiments revealed that DSF SD combined with in-situ gel(DSF SD/in-situ gel) increased the residence time and the amount of DSF penetrated through the corneal. The pharmacodynamics studies exhibited DSF SD/in-situ gel delayed the development of selenium-induced cataract at some content. These results investigated that DSF SD/in-situ gel as a drug delivery system can improve DSF ocular permeability.
基金This work was financially supported by the 973 Program(Grant No.2009CB930300)National Natural Science Foundation of China(No.81273449).
文摘In this study,a polymeric lipid nanoparticle(NP)(simplified as Lipid NP)was reported as a promising oral vaccine delivery system.The Lipid NPs composed of a hydrophobic polymeric poly(D,L-lactide-co-glycolide)(PLGA)core and a surface coating of lipid monolayer.Membrane emulsification technique was used to obtain uniform-sized Lipid NPs.Ovalbumin(OVA)was used as a model vaccine.Compared with the pure PLGA NPs,the Lipid NPs achieved higher loading capacity(LC)and entrapment efficiency(EE)for the encapsulated OVA.An in vitro oral release profile showed that the OVA-Lipid NPs were with lower initial burst and could protect the loaded OVA from the harsh gastrointestinal(GI)environment for a long time.In addition,a human microfold cell(M-cell)transcytotic assay demonstrated that due to a lipid layer structure on the particle surface,the Lipid NPs showed higher affinity to the M-cells.Since the M-cell in the intestinal epithelium played an important role in particle transportation as well as intimately associated with the underlying immune cells,the OVA-Lipid NPs effectively induced mucosal and humoral immune responses.
基金This work was supported by National Basic Research Program of China(973 Program)(2009CB930300)National Natural Science Foundation of China(81072605)Shenyang Special Fund for Exploration of Intellectual Resources.
文摘We applied a combination of inorganic mesoporous silica material,frequently used as drug carriers,and a natural organic polymer alginate(ALG),to establish a sustained drug delivery system for the poorly water-soluble drug Indomethacin(IND).Mesoporous silica nanospheres(MSNs)were synthesized using an organic template method and then functionalized with aminopropyl groups through postsynthesis.After drug loading into the pores of aninopropyl functionalized MSNs(AP-MSNs),IND loaded AP-MSNs(IND-AP-MSNs)were encapsulated by ALG through the ionic interaction.The effects of surface chemical groups and ALG layer on IND release were systematically studied using scanning electron microscopy(SEM),transmission electron microscopy(TEM),nitrogen adsorption,zetapotential analysis and TGA analysis.The surface structure and surface charge changes of the ALG encapsulated AP-MSNs(ALG-AP-MSNs)were also investigated.The results showed that sustained release of IND from the designed drug delivery system was mainly due to the blockage effect from the coated ALG.We believe that this combination will help designing oral sustained drug delivery systems for poorly water-soluble drugs.
基金National Basic Research Program of China(973 Program)(No.2015CB932100)National Natural Science Foundation of China(No.81473165)+1 种基金Liaoning Provincial Key Laboratory of Drug Preparation Design&Evaluation of Liaoning Provincial Education Department(LZ2014045)Liaoning Provincial Key Laboratory of Studying the Modern Drug preparations.
文摘To achieve GSH-responsive 5-Fluorouridine(5-FU) delivery, a novel family of nanogel drug carriers has been successfully prepared. The new class of PAHy-based nanogels was prepared by the crossing-link reaction of poly-α, β-polyasparthydrazide(PAHy) chains and 3,3′-dithiodipropionic acid(DTDPA) consisting of a redox-responsive chain network. This particle highlights recent efforts in introducing a disulfide bond to drug delivery nanogel by DTDPA,and the increased release properties of complex nanogels produced excellent glutathione(GSH)-sensitivity and significant anti-tumor therapeutic efficacy. The PAHy-based nanogels were characterized by Fourier transform infrared spectroscopy(FT-IR), dynamic light scattering(DLS)(nano-particle size ~200 nm), UV–vis spectrometry, X-ray diffraction(XRD) and differential scanning calorimetric(DSC). PAHy-based nanogels are promising controlledrelease carriers for the tumor-targeting delivery of the anticancer agent 5-Fluorouridine.
基金the National Basic Research Program of China(973 Program)(No.2009CB930300)National Natural Science Foundation of China(No.81273449).
文摘In the current study,mesoporous carbon(MC)with pore volume(1.53 cm3/g)and pore size(9.74 nm)was successfully prepared as a carrier for celecoxib(CEL).Celecoxib was loaded into the pore channels of MC using three different methods:solvent evaporation method,absorption method and physical mixing method.Solid-state characterization methods,such as SEM,TEM,BET,DSC and XRD were used to systematically investigate the process of the drug loading system.Dissolution tests were performed to examine the effects of MC on the release of CEL.Furthermore,the cytotoxicity,wound healing,migration and invasion experiments were carried out to measure the contribution of MC to the anti-tumor metastasis ability of celecoxib on MDA-MB-231 cells.The results showed that CEL could be kept in a non-crystalline state when they were incorporated into the MC using the solvent evaporation method or absorption method.The dissolution rate of CEL released from MCS(Mesoporous carbon e Celecoxib e Solvent evaporation method)and MCA(Mesoporous carbon e Celecoxib e Absorption evaporation method)was all significantly higher than that of pure CEL.The cumulative release for MCS within the 5 min was up to 51.86%.MCS enhanced the inhibitory effect of CEL on the migration and invasion of MDAMB-231 cells.
基金supported by the National Basic Research Pro-gram of China(973 Program)(No.2015CB932100)National Natural Science Foundation of China(No.81473165)Liaoning Provincial Key Laboratory of Drug Preparation De-sign&Evaluation of Liaoning Provincial Education Depart-ment(No.LZ2015068)
文摘Mesoporous silica cocoon materials(MSNCs) and MgO doped mesoporous silica cocoons(MgO-MSNCs) with the cocoon-like hierarchical morphology and different alkalinities were synthesized as carriers for acidic drugs. Indomethacin(IMC) was selected as a model drug and loaded into carriers. All materials and the drug-loaded samples were characterized by nitrogen adsorption, FTIR spectroscopy, transmission electron microscopy(TEM), powder X-Ray diffraction(XRD) and differential scanning calorimetry(DSC). The effect of the Mg/Si molar ratio on the kinetics and equilibrium of IMC adsorption on MgO-MSNCs was thoroughly examined, and it was found that the increase in the Mg/Si molar ratio resulted in an increasing IMC adsorption rate due to the increased affinity between alkaline MgO-MSNCs and weak acid IMC. The adsorption kinetics fitted a pseudo second-order model well. The Freundlich isotherm showed a better fit, indicating that the coverage of IMC on the surface of MgO-MSNCs was heterogeneous. The maximum adsorption capacity of adsorbent was calculated by the Langmuir isotherm equation. The Temkin equation provided further support that the IMC adsorption on MgO-MSNCs was dominated by a chemisorption process. MgO-MSNCs also have the advantage of allowing an adjustment of the drug release rate of weak acid drug. The cytotoxicity assay indicated good biocompatibility of MgO-MSNCs. Our research on MgO-MSNCs carriers demonstrated their potential therapeutic benefit for safe and effective management of IMC adsorption and in vitro release.
文摘In this study,phosphonate-terminated magnetic mesoporous nanoparticles(pMMSNs)was designed by incorporation of MNPs in the center of mesoporous silica nanoparticles(MSNs)and followed by grafting phosphonate group on to the surface of MMSNs.The carrier exhibited a typical superparamagnetic feature and the saturation magnetization was 4.89 emu/g measured by vibrating sample magnetometer(VSM).pMMSNs had a spherical morphology and a pore size of 2.2 nm.FromN2 adsorption-desorption analysis,pMMSNs had a surface area of 613.4 m^(2)/g and a pore volume of 0.78 cm^(3)/g.Phosphonate modification improved the colloidal stability of MMSNs,and the hydrodynamic diameter of pMMSNs was around 175 nm.The hydrophilic phosphonate group significantly enhanced the negative surface charge of MMSNs from -19.3 mV to -28.8 mV pMMSNs with more negative surface charge had a 2.3-fold higher drug loading capacity than that of MMSNs.In addition,the rate and amount of release of doxorubicin(DOX)from DOX/pMMSNs was pH-dependent and increased with the decrease of pH.At pH 7.4,the release amount was quite low and only approximately 17wt%ofDOXwasreleasedin48h.AtpH5.0and3.0,the release rate increased significantly and the release amount achieved 31 wt%and 60 wt%in 48 h,respectively.To evaluate the magnetic targeting performance ofpMMSNs,FITC labeledpMMSNswas injected into mice bearing S180 solid tumor.FITC labeledpMMSNscontrolled by an external magnetic field showed higher tumor accumulation and lower normal tissue distribution.
基金the National Basic Research Program of China(973 Program)(No.2009CB930300)National Natural Science Foundation of China(No.81273449).
文摘The purpose of this study was to develop poly(amidoamine)(PAMAM)-functionalized multi-walled carbon nanotubes(MWNTs)loaded with a poorly water-soluble drug,intended to improve the drug-loading capacity,dissolution and design a sustained release system.MWNTs were modified with a carboxyl group by acid treatment and then complex with PAMAM.PAMAM-MWNTs were investigated as a scaffold for loading the model drug,Carvedilol(CAR),using three different methods(the fusion method,the incipient wetness impregnation method,and the solvent method).The effects of different pore size,specific surface area and physical state were systematically studied using FT-IR,TGA,SEM,DSC,nitrogen adsorption,XPS and XRD.All the samples made by PAMAM-MWNTs to load the drug had a marked effect on the drug-loading capacity as well as drug dissolution,especially theⅡ-30%.
基金supported by the National Natural Science Foundation of China(81991491,32300777)the Fundamental Research Funds for the Central Universities(20720220006)+1 种基金China Postdoctoral Science Foundation(2022M722659)CAMS Innovation Fund for Medical Sciences(2019RU022).
文摘Dear Editors,Bispecific antibodies(bsAbs),which possess the unique ability to bind to two different antigens simultaneously(Labrijn et al.,2019),have emerged as powerful tools in the field of cancer immunotherapy and pathogen prevention.Their design and production are of great significance,as they can enhance the effectiveness of targeted therapy by improving the accuracy and efficiency of attacks against multiple targets.However,compared with traditional monoclonal antibodies,the design and production of bsAbs are more complex.One major challenge facing the conventional IgG bispecific format is the efficient pairing of different chains,known as the chain association issue.To overcome this,researchers have sought to promote heavychain heterodimerization through Fc engineering techniques,such as knobs-intoholes(KiH)and controlled Fab arm exchange.Others have highlighted the benefit of simple heavy-light chain paired formats,as they completely bypass the chain association issue while offering improved manufacturability.
基金supported by the Liaoning Provincial Department of Education youth project(No.LJKQZ20222355,China).
文摘Reactive oxygen species(ROS)generated from photosensitizers exhibit great potential for repolarizing immunosuppressive tumor-associated macrophages(TAMs)toward the anti-tumor M1 phenotype,representing a promising cancer immunotherapy strategy.Nevertheless,their effectiveness in eliminating solid tumors is generally limited by the instability and inadequate TAMs-specific targeting of photosensitizers.Here,a novel core-shell integrated nano platform is proposed to achieve a coordinated strategy of repolarizing TAMs for potentiating cancer immunotherapy.Colloidal mesoporous silica nanoparticles(CMSN)are fabricated to encapsulate photosensitizer-Indocyanine Green(ICG)to improve their stability.Then ginseng-derived exosome(GsE)was coated on the surface of ICG/CMSN for targeting TAMs,as well as repolarizing TAMs concurrently,named ICG/CMSN@GsE.As expected,with the synergism of ICG and GsE,ICG/CMSN@GsE exhibited better stability,mild generation of ROS,favorable specificity toward M2-like macrophages,enhancing drug retention in tumors and superior TAMs repolarization potency,then exerted a potent antitumor effect.In vivo,experiment results also confirm the synergistic suppression of tumor growth accompanied by the increased presence of anti-tumor M1-like macrophages and maximal tumor damage.Taken together,by integrating the superiorities of TAMs targeting specificity and synergistic TAMs repolarization effect into a single nanoplatform,ICG/CMSN@GsE can readily serve as a safe and high-performance nanoplatform for enhanced cancer immunotherapy.
文摘The authors regret that there is an error in the article Fig.9D1 due to the mistake of copying and pasting in the process of assembling figures and negligence in the proofreading,and also a mislabled error in the supporting Information Fig.S9 and S10.
基金financially supported by the National Basic Research Program of China(2015CB932103)the National Natural Science Foundation of China(31771092,81521005,81690265)the Youth Innovation Promotion Association of Chinese Academy of Sciences and Fudan-SIMM Joint Research Fund(FU-SIMM20182005,China).
文摘The limited penetration of nanoparticles and their poor accessibility to cancer cell fractions in tumor remain essential challenges for effective anticancer therapy.Herein,we designed a targeting peptide-decorated biomimetic lipoprotein(termed as BL-RD)to enable their deep penetration and efficient accessibility to cancer cell fractions in a tumor,thereby improving the combinational chemophotodynamic therapy of triple negative breast cancer.BL-RD was composed of phospholipids,apolipoprotein A1 mimetic peptide(PK22),targeting peptide-conjugated cytotoxic mertansine(RM)and photodynamic agents of DiIC18(5)(DiD).The counterpart biomimetic lipoprotein system without RM(termed as BL-D)was fabricated as control.Both BL-D and BL-RD were nanometer-sized particles with a mean diameter of less than 30 nm and could be efficiently internalized by cancer cells.After intravenous injection,they can be specifically accumulated at tumor sites.When comparing to the counterpart BLD,BL-RD displayed superior capability to permeate across the tumor mass,extravasate from tumor vasculature to distant regions and efficiently access the cancer cell fractions in a solid tumor,thus producing noticeable depression of the tumor growth.Taken together,BL-RD can be a promising delivery nanoplatform with prominent tumor-penetrating and cancer cells-accessing capability for effective tumor therapy.
基金This work was supported by China Postdoctoral Science Foundation(No.2020T130434,China)National Natural Science Foundation of China(No.82073798,China)+2 种基金National Natural Science Foundation of China(No.82104107,China)National Basic Research Program of China(973 Program)(No.2015CB932100,China)Doctoral Start-up Foundation of Liaoning Province(No.2021-BS-127,China).
文摘Utilization of the intestinal lymphatic pathway will allow extraordinary gains in lymph and tumors cascade-targeted delivery of oral drugs and awakening the innate/adaptive immunity of the body and the lesion microenvironment,in addition to improving oral bioavailability relative to other means of delivery of oral drugs.Here,inspired by the specific invasion route of intestinal microorganisms,we pioneered an immune-awakening Saccharomyces-inspired mesoporous silicon nanoparticle(yMSN)for the ingenious cascade-targeted delivery of therapeutic cancer vaccines and antitumor drugs to lymph and tumors via the intestinal lymphatic pathway.Encouragingly,yMSN high-loaded tumor-specific antigens(OVA,11.9%)and anti-tumor drugs(Len,28.6%)with high stability,namely Len/OVA/yMSN,efficiently co-delivered OVA and Len to their desired target sites.Moreover,yMSN concomitantly awakened the innate antitumor immunity of dendritic cells and macrophages,strengthening vaccine-induced adaptive immune responses and reversing macrophage-associated immunosuppression in the tumor microenvironment.Surprisingly,Len/OVA/yMSN treatment resulted in excellent synergistic antitumor efficacy and long-term antitumor memory in OVA-Hepa1-6-bearing mice.This high-performance nanocarrier provides a novel approach for lesion-targeting delivery of oral drugs accompanied with awakening of the innate/adaptive immunity of the lesion environment,and also represents a novel path for the oral delivery of diverse therapeutic agents targeting other lymph-mediated diseases.
基金This work was supported by grants from the National Key Research and Development Program of China(grant no.2022YFC0869900)the National Natural Science Foundation of China(grant nos.81991491,82272305)+2 种基金the Fundamental Research Funds for the Central Universities(grant no.20720220006)China Postdoctoral Science Foundation(grant nos.2022M722659)CAMS Innovation Fund for Medical Sciences(grant no.2019RU022).
文摘Dear Editor As of January 2023,coronavirus disease 2019(COVID-19)induced by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused more than 6.7 million deaths,with SARS-CoV-2 variants continuing to alter the trajectory of the COVID-19 pandemic.Indeed,the prevalence of the newly emergent Omicron sublineages,particularly BA.4/5 and XBB,has highlighted the critical need for the design and production of broadly potent neutralization antibodies to efficiently combat SARS-CoV-2 variants.Neutralizing antibodies(nAbs)XMA01,XMA04,and XMA09,which target noncompeting antigenic sites in RBD(receptor binding domain),exhibit high neutralization potency against earlier disease variants(Supplementary Fig.1a–d),as previously reported by us.
