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| 1 | Mesoporous silica nanoparticles for drug and gene delivery显示文摘Mesoporous silica nanoparticles(MSNs) are attracting increasing interest for potential biomedical applications. With tailored mesoporous structure, huge surface area and pore volume,selective surface functionality, as well as morphology control, MSNs exhibit high loading capacity for therapeutic agents and controlled release properties if modified with stimuli-responsive groups, polymers or proteins. In this review article, the applications of MSNs in pharmaceutics to improve drug bioavailability, reduce drug toxicity, and deliver with cellular targetability are summarized. Particularly,the exciting progress in the development of MSNs-based effective delivery systems for poorly soluble drugs, anticancer agents, and therapeutic genes are highlighted. | Yixian Zhou Guilan Quan Qiaoli Wu Xiaoxu Zhang Boyi Niua Biyuan Wu Ying Huang Xin Pan Chuanbin Wu | 2018 | Acta Pharmaceutica Sinica B2018，8，2： | 31 |
| 2 | Synergistic immunoreaction of acupuncture-like dissolving microneedles containing thymopentin at acupoints in immune-suppressed rats显示文摘Dissolving microneedles carried drug molecules can effectively penetrate the stratum corneum of skin to improve the transdermal drug delivery. The traditional Chinese medicine acupuncture is based on the needle stimulation at a specific location(acupoint) to generate and transmit biochemical and physiological signals which alter the pathophysiological state of patients. However, the pain associated with conventional acupuncture needles and the requirement of highly trained professionals limit the development of acupuncture in non-Asian countries. The purpose of this study is to investigate whether the dissolving microneedles can be utilized as a self-administered painless replacement for acupuncture and locally released drug molecules can achieve expected therapeutic outcomes. Immunosuppressive rats were treated with acupuncture at Zusanli(ST36) acupoint using microneedles containing thymopentin.The immune functions and psychological mood of the immunosuppressed animals were examined. The proliferation of splenocytes was examined by CCK-8 assay. CD4 and CD8 expression patterns in spleen cells were detected by flow cytometry. The current study showed that use of either microneedles containing thymopentin or conventional acupuncture both resulted in immune cell proliferation, which was confirmed by flow cytometry. Furthermore, either conventional acupuncture or microneedles were able to effectively mitigate the anxiety caused by immune-suppression when applied on the ST36. | Qian Zhang Chuncao Xu Shiqi Lin Huanbin Zhou Gangtao Yao Hu Liu Lili Wang Xin Pan Guilan Quan Chuanbin Wu | 2018 | Acta Pharmaceutica Sinica B2018，8，3： | 9 |
| 3 | Bilayer dissolving microneedle array containing 5-fluorouracil and triamcinolone with biphasic release profile for hypertrophic scar therapy显示文摘Hypertrophic scar(HS)is an undesirable skin abnormality following deep burns or operations.Although intralesional multi-injection with the suspension of triamcinolone acetonide(TA)and 5-fluorouracil(5-Fu)has exhibited great promise to HS treatment in clinical,the difference of metabolic behavior between TA and 5-Fu remarkably compromised the treatment efficacy.Besides,the traditional injection with great pain is highly dependent on the skill of the experts,which results in poor compliance.Herein,a bilayer dissolving microneedle(BMN)containing TA and 5-Fu(TA-5-Fu-BMN)with biphasic release profile was designed for HS therapy.Equipped with several micro-scale needle tips,the BMN could be self-pressed into the HS with uniform drug distribution and less pain.Both in vitro permeation and in vivo HS retention tests revealed that TA and 5-Fu could coexist in the scar tissue for a sufficient time period due to the well-designed biphasic release property.Subsequently,the rabbit ear HS model was established to assess therapeutic efficacy.The histological analysis showed that TA-5-Fu-BMN could significantly reduce abnormal fibroblast proliferation and collagen fiber deposition.It was also found that the value of scar elevation index was ameliorated to a basal level,together with the downregulation of mRNA and protein expression of Collagen I(Col I)and transforming growth factor-β1(TGF-β1)after application of TA-5-Fu-BMN.In conclusion,the BMN with biphasic release profiles could serve as a potential strategy for HS treatment providing both convenient administrations as well as controlled drug release behavior. | Beibei Yang Yating Dong Yifeng Shen Ailin Hou Guilan Quan Xin Pan Chuanbin Wu | 2021 | Bioactive Materials2021，6，8： | 8 |
| 4 | Development of composite PLGA microspheres containing exenatide-encapsulated lecithin nanoparticles for sustained drug release显示文摘This study aimed to prepare poly(D, L-lactic-co-glycolic acid) microspheres(PLGA-Ms)by a modified solid-in-oil-in-water(S/O/W) multi-emulsion technique in order to achieve sustained release with reduced initial burst and maintain efficient drug concentration for a prolonged period of time. Composite PLGA microspheres containing exenatideencapsulated lecithin nanoparticles(Ex-NPs-PLGA-Ms) were obtained by initial fabrication of exenatide-loaded lecithin nanoparticles(Ex-NPs) via the alcohol injection method,followed by encapsulation of Ex-NPs into PLGA microspheres. Compared to Ms prepared by the conventional water-in-oil-in-water(W/O/W) technique(Ex-PLGA-Ms), Ex-NPs-PLGAMs showed a more uniform particle size distribution, reduced initial burst release, and sustained release for over 60 d in vitro. Cytotoxicity studies showed that Ms prepared by both techniques had superior biocompatibility without causing any detectable cytotoxicity.In pharmacokinetic studies, the effective drug concentration was maintained for over 30 d following a single subcutaneous injection of two types of Ms formulation in rats, potentially prolonging the therapeutic action of Ex. In addition, administration of Ex-NPs-PLGA-Ms resulted in a more smooth plasma concentration-time profile with a higher area under the curve(AUC) compared to that of Ex-PLGA-Ms. Overall, Ex-NPs-PLGA-Ms prepared by the novel S/O/W method could be a promising sustained drug release system with reduced initial burst release and prolonged therapeutic efficacy. | Ni Dong Chune Zhu Junhuang Jiang Di Huang Xing Li Guilan Quan Yang Liu Wen Tan Xin Pan Chuanbin Wu | 2020 | Asian Journal of Pharmaceutical Sciences2020，15，3： | 7 |
| 5 | “Pincer movement”:Reversing cisplatin resistance based on simultaneous glutathione depletion and glutathione S-transferases inhibition by redox-responsive degradable organosilica hybrid nanoparticles显示文摘The therapeutic efficacy of cisplatin has been restricted by drug resistance of cancers.Intracellular glutathione(GSH)detoxification of cisplatin under the catalysis of glutathione S-transferases(GST)plays important roles in the development of cisplatin resistance.Herein,a strategy of“pincer movement”based on simultaneous GSH depletion and GST inhibition is proposed to enhance cisplatin-based chemotherapy.Specifically,a redox-responsive nanomedicine based on disulfide-bridged degradable organosilica hybrid nanoparticles is developed and loaded with cisplatin and ethacrynic acid(EA),a GST inhibitor.Responding to high level of intracellular GSH,the hybrid nanoparticles can be gradually degraded due to the break of disulfide bonds,which further promotes drug release.Meanwhile,the disulfide-mediated GSH depletion and EA-induced GST inhibition cooperatively prevent cellular detoxification of cisplatin and reverse drug resistance.Moreover,the nanomedicine is integrated into microneedles for intralesional drug delivery against cisplatin-resistant melanoma.The in vivo results show that the nanomedicine-loaded microneedles can achieve significant GSH depletion,GST inhibition,and consequent tumor growth suppression.Overall,this research provides a promising strategy for the construction of new-type nanomedicines to overcome cisplatin resistance,which extends the biomedical application of organosilica hybrid nanomaterials and enables more efficient chemotherapy against drug-resistant cancers. | Boyi Niu Yixian Zhou Kaixin Liao Ting Wen Sixian Lao Guilan Quan Xin Pan Chuanbin Wu | 2022 | Acta Pharmaceutica Sinica B2022，12，4： | 3 |
| 6 | Self-assembly nanomicelle-microneedle patches with enhanced tumor penetration for superior chemo-photothermal therapy显示文摘Nanomedicine with high specificity has been a promising tool for cancer diagnosis and therapy.However,the successful application of nanoparticle-based superficial cancer therapy is severely hindered by restricted deep tumor tissue accumulation and penetration.Herein,a self-assembly nanomicelle dissolving microneedle(DMN)patch according to the“nano in micro”strategy was conducted to co-deliver a first-line chemotherapeutic agent paclitaxel(PTX),and a photosensitizer IR780(PTX/IR780-NMs@DMNs)for chemo-photothermal synergetic melanoma therapy.Upon direct insertion into the tumor site,DMNs created a regular and multipoint three-dimensional drug depot to maximize the tumor accumulation.Accompanied by the DMN dissolution,the composition of the needle matrixes self-assembled into nanomicelles,which could efficiently penetrate deep tumor tissue.Upon laser irradiation,the nanomicelles could not only ablate tumor cells directly by photothermal conversion but also trigger PTX release to induce tumor cell apoptosis.In vivo results showed that compared with intravenous injection,IR780 delivered by PTX/IR780-NMs@DMNs was almost completely accumulated at the tumor site.The antitumor results revealed that the PTX/IR780-NMs@DMNs could effectively eliminate tumors with an 88%curable rate without any damage to normal tissues.This work provides a versatile and generalizable framework for designing self-assembly DMN-mediated combination therapy to fight against superficial cancer. | Ying Sun Minglong Chen Dan Yang Wanbing Qin Guilan Quan Chuanbin Wu Xin Pan | 2022 | Nano Research2022，15，3： | 2 |
| 7 | Optimization of a doxycycline hydroxypropyl-β-cyclodextrin inclusion complex based on computational modeling显示文摘To prepare a stable complex of doxycycline(Doxy)and hydroxypropy-β-cyclodextrin(HP-β-CD)for ophthalmic delivery,the optimum formulation and preparation conditions were investigated using response surface methodology(RSM),artificial neural network(ANN)and support vector machine(SVM)modeling.The molar ratios of HP-β-CD/Doxy and Mg^(2+)/Doxy,inclusion time and temperature were selected as independent variables (X_(1)-X_(4)) and inclusion efficiency and stability of the Doxy-HP-β-CD complex were selected as dependent(response)variables(Y_(1) and Y_(2)).The optimal formulation predicted by genetic algorithm(GA)combined with the models was characterized by microscopy and nuclear magnetic resonance spectrometry,and the stability of Doxy in the complex was evaluated.The highest values of Y_(1) and Y_(2) were obtained using an ANN model combined with GA which predicted the values of X_(1)-X_(4) to be 4,10.8,12 h and 25℃,respectively.The modeling and optimization results indicated that a feed-forward back-propagation ANN with one hidden layer and 10 hidden units showed better fitting to both responses compared to the RSM and SVM models.GA proved to be an efficient tool in multiobjective optimization of a pharmaceutical formulation. | Zhouhua Wang Zixin He Lei Zhang Haohao Zhang Meimei Zhang Xinguo Wen Guilan Quan Xintian Huang Xin Pan Chuanbin Wu | 2013 | Acta Pharmaceutica Sinica B2013，3，2： | 2 |
| 8 | Virus-inspired surface-nanoengineered antimicrobial liposome:A potential system to simultaneously achieve high activity and selectivity显示文摘Enveloped viruses such as SARS-CoV-2 frequently have a highly infectious nature and are considered effective natural delivery systems exhibiting high efficiency and specificity.Since simultaneously enhancing the activity and selectivity of lipopeptides is a seemingly unsolvable problem for conventional chemistry and pharmaceutical approaches,we present a biomimetic strategy to construct lipopeptide-based mimics of viral architectures and infections to enhance their antimicrobial efficacy while avoiding side effects.Herein,a surface-nanoengineered antimicrobial liposome(SNAL)is developed with the morphological features of enveloped viruses,including a moderate size range,lipid-based membrane structure,and highly lipopeptide-enriched bilayer surface.The SNAL possesses virus-like infection to bacterial cells,which can mediate high-efficiency and high-selectivity bacteria binding,rapidly attack and invade bacteria via plasma membrane fusion pathway,and induce a local“burst”release of lipopeptide to produce irreversible damage of cell membrane.Remarkably,viral mimics are effective against multiple pathogens with low minimum inhibitory concentrations(1.6-6.3μg mL1),high bactericidal efficiency of>99%within 2 h,>10-fold enhanced selectivity over free lipopeptide,99.8%reduction in skin MRSA load after a single treatment,and negligible toxicity.This bioinspired design has significant potential to enhance the therapeutic efficacy of lipopeptides and may create new opportunities for designing next-generation antimicrobials. | Yin Shi Xiaoqian Feng Liming Lin Jing Wang Jiaying Chi Biyuan Wu Guilin Zhou Feiyuan Yu Qian Xu Daojun Liu Guilan Quan Chao Lu Xin Pan Jianfeng Cai Chuanbin Wu | 2021 | Bioactive Materials2021，6，10： | 1 |
| 9 | Role of autoreactive Tc17 cells in the pathogenesis of experimental autoimmune encephalomyelitis显示文摘Background:The pathogenesis of multiple sclerosis(MS)and experimental autoimmune encephalomyelitis(EAE-an animal model of MS)is primarily mediated by T cells.However,recent studies have only focused on interleukin(IL)-17-secreting CD4^(+)T-helper cells,also known as Th17 cells.This study aimed to compare Th17 cells and IL-17-secreting CD8^(+)T-cytotoxic cells(Tc17)in the context of MS/EAE.Methods:Female C57BL/6 mice were immunized with myelin oligodendrocyte glycoprotein peptides 35-55(MOG35-55),pertussis toxin,and complete Freund's adjuvant to establish the EAE animal model.T cells were isolated from the spleen(12-14 days postimmunization).CD4^(+)and CD8^(+)T cells were purified using isolation kit and then differentiated into Th17 and Tc17,respectively,using MOG35-55 and IL-23.The secretion levels of interferon-(IFN-γ)and IL-17 were measured via enzyme-linked immunosorbent assay using cultured CD4^(+)and CD8^(+)T cell supernatants.The pathogenicity of Tc17 and Th17 cells was assessed through adoptive transfer(tEAE),with the clinical course assessed using an EAE score(0-5).Hematoxylin and eosin as well as Luxol fast blue staining were used to examine the spinal cord.Purified CD8^(+)CD3^(+)and CD4^(+)CD3^(+)cells differentiated into Tc17 and Th17 cells,respectively,were stimulated with MOG35-55 peptide for proliferation assays.Results:The results showed that Tc17 cells(15,951±19855VS.55,709±4196cpm;p<0.050)exhibited a weaker response to highest dose(20μg/mL)MOG35-55 than Th17 cells.However,this response was not dependent on Th17 cells.After the 48h stimulation,at the highest dose(20μg/mL)of MOG35-55.Tc17 cells secreted lower levels of IFN-(280.00±15.00vs.556.67±15.28pg/mL,p<0.050)and IL-17(102.67±5.86 pg/mL vs.288.33±12.58 pg/mL;p<0.050)than Th17 cells.Similar patterns were observed for IFN-γsecretion at 96 and 144h.Furthermore,Tc17 cell-induced tEAE mice exhibited similar EAE scores to Th17 cell-induced tEAE mice and also showed similar inflammation and demyelination.Conclusion:The degree of pathogenicity of Tc17 cells in EAE is lower than that of Th17 cells.Future investigation on different immune cells and EAE models is warranted to determine the mechanisms underlying MS. | Yong Peng Xiuli Zhang Yandan Tang Shunqing He Guilan Rao Quan Chen Yahui Xue Hong Jin Shu Liu Ziyang Zhou Yun Xiang | 2024 | Neuroprotection2024，2，1： | 0 |
| 10 | A triple-enhanced chemodynamic approach based on glucosepowered hybrid nanoreactors for effective bacteria killing显示文摘Rapid evolution of multidrug resistance in bacterial pathogens is outpacing the development of new antibiotics,and chemodynamic therapy(CDT)provides an excellent alternative.However,achieving highly efficient CDT is still a great challenge,since the pH in the infection site is close to neutral and the supply of H_(2)O_(2)is inadequate.We herein constructed the antibacterial nanoreactors.Indocyanine green(ICG)and glucose oxidase(GOx)were incorporated into homologous zeolitic imidazolate framework-8(ZIF-8)nanoparticles coating with metal polyphenol network(MPN)composed by Fe^(3+)and tannic acid(TA).The well-designed nanoreactors could simultaneously break the pH and H_(2)O_(2)limitations,and generate hyperthermia under irradiation,thus realizing a triple-enhanced CDT for high-efficiency sterilization.Furthermore,the nanoreactors could combine CDT with photothermal therapy(PTT)and photodynamic therapy(PDT),which not only improved the bactericidal efficiency and broadened the antibacterial spectrum,but also alleviated the antibiotics resistance issues.Remarkably,the proposed nanoreactors achieved a robust in vitro bacterial killing against Gram-positive methicillin-resistant Staphylococcus aureus(MRSA)and Gram-negative Pseudomonas aeruginosa.The nanoreactors achieved an 99.7%MRSA reduction in an MRSA-induced murine abscess model accompanied with negligible toxicity.Overall,this study provides a promising strategy for multiple-enhanced CDT and multimodal combined therapy for pathogenic infections. | Jintao Fu Yixian Zhou Ting Liu Wenhao Wang Yiting Zhao Ying Sun Yiming Zhang Wenxuan Qin Zhongwei Chen Chao Lu Guilan Quan Chuanbin Wu Xin Pan | 2023 | Nano Research2023，16，2： | 0 |
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