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Doxorubicin hydrochloride and L-arginine co-loaded nanovesicle for drug resistance reversal stimulated by near-infrared light

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Asian Journal of Pharmaceutical Sciences 2022年第6期17卷 924-937页

作者： Linping Jiang Kesi Wang Liyan Qiu Ministry of Educational(MOE)Key Laboratory of Macromolecular Synthesis and Functionalization Department of Polymer Science and EngineeringZhejiang UniversityHangzhou 310027China

Drug resistance is accountable for the inadequate outcome of chemotherapy in clinics.The newly emerging role of nitric oxide(NO)to conquer drug resistance has been recognized as a potential strategy.However,it remains a great challenge to realize targeted delivery as well as accurate release of NO at desired sites.Herein,we developed a PEGylated indocyanine green(m PEG-ICG)integrated nanovesicle system(PIDA)to simultaneously load doxorubicin hydrochloride(DOX·HCl)and the NO donor L-arginine(L-Arg),which can produce NO triggered by NIR light irradiation and exert multimodal therapy to sensitize drug-resistant cancers.Upon 808 nm irradiation,the NO released from PIDA led to a decrease in mitochondrial membrane potential,an increase in ROS and significant ATP depletion in K562/ADR cells,thus inhibiting cell growth and resolving the problem of drug resistance.Consequently,the in vivo experiment on K562/ADR-bearing nude mice indicated that PIDA nanovesicles achieved significant anticancer efficacy with a tumor inhibition rate of 80.8%.Above all,PIDA nanovesicles offer guidance for designing nanoplatforms for drug-resistant cancer treatment.

关键词： Nitric oxide L-arginine Doxorubicin Indocyanine green Drug resistance nanovesicle

Co-delivery of Doxorubicin and Afatinib with pH-responsive Polymeric nanovesicle for Enhanced Lung Cancer Therapy

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Chinese Journal of Polymer Science 2019年第12期37卷 1224-1233,I0006页

作者： Heng-Ye Gong Yan-Gui Chen Xing-Su Yu Hong Xiao Jin-Peng Xiao Yong Wang Xin-Tao Shuai PCFM Lab of Ministry of Education School of Materials Science and EngineeringSun Yat-Sen UniversityGuangzhou 510275China HEC Pharma Co. Ltd.Dongguan 523871China Reproductive Center Guangdong Women’s Health Care CenterGuangzhou 511400China

Drug-resistance and drastic side effects are two major issues of traditional chemotherapy which may result in trail failure even death.Nanoparticle-mediated multidrug combination treatment has been proven to be a feasible strategy to overcome these challenges.In the present study,amphipathic block polymer of methoxyl poly(ethylene glycol)-poly(aspartyl(dibutylethylenediamine)-co-phenylalanine)(m PEG-P(Asp(DBA)-co-Phe))was synthesized and self-assembled into p H-responsive polymeric vesicle.The vesicle was utilized to co-deliver cancer-associated epidermal growth factor(EGFR)inhibitor of afatinib and DNA-damaging chemotherapeutic doxorubicin hydrochloride(DOX)for enhanced non-small-cell lung cancer(NSCLC)therapy.As evaluated in vitro,the p H-responsive design of nanovesicle resulted in a rapid release of encapsulated drugs into tumor cells and caused enhanced cell apoptosis.In addition,in vivo therapeutic studies were conducted and the results evidenced that the co-delevery of DOX and afatinib using p H-sensitive nanovector was a promising strategy for NSCLC treatment.

关键词： nanovesicle Polymeric vector Combination therapy pH-responsive

Engineering SIRPα cellular membrane-based nanovesicles for combination immunotherapy

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Nano Research 2023年第5期16卷 7355-7363页

作者： Mingyue Wang Yanfang Wang Yeteng Mu Fuxu Yang Zebin Yang Yuxuan Liu Lili Huang Shi Liu Xingang Guan Zhigang Xie Zhen Gu School of Medicine Taizhou UniversityTaizhou 318000China College of Medical Technology Beihua UniversityJilin 132013China Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Jinhua Institute of Zhejiang University Jinhua 321299China State Key Laboratory of Polymer Physics and Chemistry Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China Department of General Surgery Sir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhou 310016China Zhejiang Laboratory of Systems&Precision Medicine Zhejiang University Medical CenterHangzhou 311121China MOE Key Laboratory of Macromolecular Synthesis and Functionalization Department of Polymer Science and EngineeringZhejiang UniversityHangzhou 310027China

Immune checkpoint inhibitors(ICIs)have revolutionized cancer treatment for their unprecedented clinical efficacy.Signal regulatory proteinα(SIRPα)is a phagocytic checkpoint expressed on macrophages,dendritic cells,other myeloid cells.Cancer cells inhibit macrophage phagocytosis through the interaction of the CD47-SIRPαaxis.Disrupting the CD47-SIRPαaxis has therefore been a promising strategy in restoring the immune attack against cancer.Herein,we engineered cellular membrane nanovesicles(NVs)presenting SIRPαreceptors for phagocytosis checkpoint blockade to augment the antitumor immune response.Furthermore,zebularine(Zeb),an inhibitor of DNA methyltransferase,was encapsulated into SIRPαNVs to reprogram the immunosuppressive tumor microenvironment together with blockade of phagocytosis checkpoint.It is demonstrated that SIRPα@Zeb can improve tumor immunogenicity,the polarization of tumor-associated macrophages to the M1 phenotype,increase the infiltration of CD8^(+)T lymphocytes in tumors.The robust antitumor immune response induced by SIRPα@Zeb significantly suppressed tumor growth and extended mice-bearing melanoma xenograft survival.

关键词： drug delivery signal regulatory proteinα nanovesicle tumor-associated macrophages cancer immunotherapy

利用"Find-eat"策略通过受体功能化凋亡小体纳米囊泡靶向内皮细胞

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Science Bulletin 2023年第8期68卷 826-837,M0004页

作者：钱姝桐毛佳怡赵秋羽赵彬帆刘芷默卢博伦张柳成毛曦媛张余光王丹茹孙晓明崔文国 Department of Plastic and Reconstructive Surgery Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China Department of Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint DiseasesShanghai Institute of Traumatology and OrthopaedicsRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China

慢性创面的缺氧微环境导致血管化不足,进而使得伤口延迟愈合.内皮细胞作为组成新生血管的关键细胞,在血管化过程中发挥着核心作用.本研究构建了CX3CR1功能化凋亡小体纳米囊泡(nABs).“Find-eat”策略通过受体-配体组合,靶向低氧微环境... 详细信息

慢性创面的缺氧微环境导致血管化不足,进而使得伤口延迟愈合.内皮细胞作为组成新生血管的关键细胞,在血管化过程中发挥着核心作用.本研究构建了CX3CR1功能化凋亡小体纳米囊泡(nABs).“Find-eat”策略通过受体-配体组合,靶向低氧微环境中高表达CX3CR1的内皮细胞(ECs),从而放大“Find-eat”信号,促进血管生成.作者首先通过化学诱导脂肪干细胞(ADSCs)凋亡获得ABs,然后通过优化的低渗处理-温和超声-药物混合-挤压一系列处理步骤,获得载有去铁胺(DFO)的功能化凋亡小体纳米囊泡.体外实验显示ABs纳米囊泡生物相容性良好;可以通过CX3CL1/CX3CR1诱导缺氧微环境中的内皮细胞实现对其的“Find-eat”,进而促进内皮细胞的增殖、迁移、成管能力.体内实验中,ABs纳米囊泡可以促进伤口快速闭合,并可通过释放“Find-eat”信号靶向内皮细胞的同时实现促血管药物的缓释,促进糖尿病大鼠创面的新生血管形成.这种能够通过释放双重信号靶向内皮细胞并实现促血管药物缓释的ABs纳米囊泡为慢性糖尿病创面的愈合提供了一种新思路.

关键词： Endothelialcell-targeted Apoptotic body nanovesicle Dual signal

Delivery of Survivin siRNA Using Cationic Diphenylalanine Vesicles

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Chemical Research in Chinese Universities 2019年第3期35卷 434-439页

作者： GUAN Shuwen YU Xiaoxuan LI Junyang XU Heng HAN Wenzhao SHI Guannan XU Jia WANG Liping School of Life Sciences Jilin UniversityChangchun 130012P.R.China College of Chemistry Jilin UniversityChangchun 130012P.R.China

Small interfering RNA(siRNA) has been proved to be a powerful tool for silencing target gene in cells, raising the possibility that siRNA can be employed as a therapy for treating cancers and other genetic diseases. However, siRNA transfection has the limitation due to the difficulty in the delivery of siRNA to target cells and tissues. To explore an efficient biocompatible siRNA delivery system, cationic diphenylalanine vesicles(CDPVs) were constructed to transfer survivin siRNA to human ovarian cancer cells. The morphology of CDPVs was characterized by scanning electron microscopy(SEM) and the distribution of survivin siRNA was characterized by confocal laser scanning microscopy, which reveal that diphenylalanine and the survivin siRNA were successfully co-delivered. After co-incubation for 48 h, the CDPVs/siRNA exhibited enhanced tumor cell growth inhabitation and apoptosis inducted in human SK-OV-3 ovarian carcinoma cells. Overall, CDPVs is an efficient siRNA delivery system and has a promising prospect for cancer therapy.

关键词： siRNA delivery Cationic diphenylalanine nanovesicle Cancer therapy