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GSH-responsive SN38 dimer-loaded shape-transformable nanoparticles with iRGD for enhancing chemo-photodynamic therapy

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Acta Pharmaceutica Sinica B 2020年第12期10卷 2348-2361页

作者： Congcong Lin Fan Tong Rui Liu Rou Xie Ting Lei Yuxiu Chen Zhihang Yang huile gao Xiangrong Yu Department of Radiology Zhuhai People’s HospitalJinan UniversityZhuhai 519000China Department of Medicinal Chemistry and Natural Medicine Chemistry College of PharmacyHarbin Medical UniversityHarbin 150081China Key Laboratory of Drug Targeting and Drug Delivery Systems West China School of PharmacySichuan UniversitySichuan 610041China

Accurate tumor targeting,deep penetration and superb retention are still the main pursuit of developing excellent *** achieve these requirements,a stepwise stimuli-responsive strategy was developed through co-administration tumor penetration peptide iRGD with shape-transformable and GSH-responsive SN38-dimer(d-SN38)-loaded nanoparticles(d-SN38@NPs/iRGD).Upon intravenous injection,d-SN38@NPs with high drug loading efficiency(33.92±1.33%)could effectively accumulate and penetrate into the deep region of tumor sites with the assistance of *** gathered nanoparticles simultaneously transformed into nanofibers upon 650 nm laser irradiation at tumor sites so as to promote their retention in the tumor and burst release of reactive oxygen species for photodynamic *** loaded d-SN38 with disulfide bond responded to the high level of GSH in tumor cytoplasm,which consequently resulted in SN38 release and excellent chemo-photodynamic effect on *** vitro,coadministering iRGD with d-SN38@NPs+laser showed higher cellular uptake,apoptosis ratio and multicellular spheroid *** vivo,d-SN38@NPs/iRGD+laser displayed advanced penetration and accumulation in tumor,leading to 60.89%of tumor suppression in 4 T1 tumor-bearing mouse model with a favorable toxicity *** new strategy combining iRGD with structural transformable nanoparticles greatly improves tumor targeting,penetrating and retention,and empowers anticancer efficacy.

关键词： Shape-transformable SN38 dimer GSH-responsive Chemo-photodynamic therapy iRGD Co-administration Ce6 Breast cancer

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Self-propelled nanomotor reconstructs tumor microenvironment through synergistic hypoxia alleviation and glycolysis inhibition for promoted anti-metastasis

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Acta Pharmaceutica Sinica B 2021年第9期11卷 2924-2936页

作者： Wenqi Yu Ruyi Lin Xueqin He Xiaotong Yang Huilin Zhang Chuan Hu Rui Liu Yuan Huang Yi Qin huile gao Industrial Technology West China School of PharmacySichuan UniversityChengdu 610041China Department of Orthopedics Zhuhai HospitalJinan UniversityZhuhai People’s HospitalGuangdong 519000China

Solid tumors always exhibit local hypoxia,resulting in the high metastasis and inertness to *** of hypoxic tumor microenvironment(TME)is considered a potential therapy compared to directly killing tumor ***,the insufficient oxygen delivery to deep tumor and the confronting Warburg effect"compromise the efficacy of hypoxia ***,we construct a cascade enzyme-powered nanomotor(NM-si),which can simultaneously provide sufficient oxygen in deep tumor and inhibit the aerobic glycolysis to potentiate anti-metastasis in ***(Cat)and glucose oxidase(GOx)are co-adsorbed on our previously reported CAuNCs@HA to form self-propelled nanomotor(NM),with hexokinase-2(HK-2)siRNA further condensed(NM-si).The persistent production of oxygen bubbles from the cascade enzymatic reaction propels NM-si to move forward autonomously and in a controllable direction along H_(2)O_(2) gradient towards deep tumor,with hypoxia successfully alleviated in the *** autonomous movement also facilitates NM-si with lysosome escaping for efficient HK-2 knockdown to inhibit *** vivo results demonstrated a promising anti-metastasis effect of commercially available albumin-bound paclitaxel(PTX@HSA)after pre-treated with NM-si for TME *** cascade enzyme-powered nanomotor provides a potential prospect in reversing the hypoxic TME and metabolic pathway for reinforced anti-metastasis of chemotherapy.

关键词： Nanomotor Microenvironment modulation Hypoxia Aerobic glycolysis Triple negative breast cancer Anti-metastasis Enzyme-powered Chemotherapy

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Scavenger receptor A-mediated nanoparticles target M1 macrophages for acute liver injury

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Asian Journal of Pharmaceutical Sciences 2023年第3期18卷 118-131页

作者： Rongping Zhang Shiqing Luo Ting Zhao Mengying Wu Lu Huang Ling Zhang Yuan Huang huile gao Xun Sun Tao Gong Zhirong Zhang Key Laboratory of Drug Targeting and Drug Delivery Systems Ministry of EducationSichuan UniversityChengdu 610041China College of Polymer Science and Engineering Sichuan UniversityChengdu 610041China

Acute liver injury(ALI)has an elevated fatality rate due to untimely and ineffective ***,schisandrin B(SchB)has been extensively used to treat diverse liver diseases,its therapeutic efficacy on ALI was limited due to its high *** acid-modified serum albumin(PSA)is not only an effective carrier for hydrophobic drugs,but also has a superb targeting effect via scavenger receptor-A(SR-A)on the M1 macrophages,which are potential therapeutic targets for *** with the common macrophage-targeted delivery systems,PSA enables site-specific drug delivery to reduce off-target ***,we prepared SchB-PSA nanoparticles and further assessed their therapeutic effect on *** vitro,compared with human serum albumin encapsulated SchB nanoparticles(SchB-HSA NPs),the SchB-PSA NPs exhibited more potent cytotoxicity on lipopolysaccharide(LPS)stimulated Raw264.7(LAR)cells,and LAR cells took up PSA NPs 8.79 times more than HSA *** expected,the PSA NPs also accumulated more in the ***,SchB-PSA NPs dramatically reduced the activation of NF-κB signaling,and significantly relieved inflammatory response and hepatic ***,the high dose of SchB-PSA NPs improved the survival rate in 72 h of ALI mice to 75%.Hence,SchB-PSA NPs are promising to treat ALI.

关键词： Acute liver injury M1 macrophages Schisandrin B Palmitic acid-modified human serum albumin

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Legumain-responsive aggregation of gold nanoparticles for enhanced retention in tumor via click cycloaddition

Legumain-responsive aggregation of gold nanoparticles for en...

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2016年中国药学大会暨第十六届中国药师周

作者： Shaobo Ruan Qin He huile gao Key Laboratory of Drug Targeting and Drug Delivery Systems West China School of PharmacySichuan University

＜正＞Designing a nanocarrier that can accumulate in tumor with preferential retention has been a majorgoalincontemporaryoncology.1,2Therefore,understandingtheprinciplesgoverning thedeliveryofnanoparticlesforpreferentialretentionisessentialforcancertherapyand detection.3 Here, we propose a size-increasing strategy based on biorespnsive nanoplatform,

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Non-invasive in vivo diagnosis of brain glioma using RGD decorated fluorescent carbonaceous nanospheres

Non-invasive in vivo diagnosis of brain glioma using RGD dec...

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2014年中国药学大会暨中国药师周

作者： Shaobo Ruan Qin He huile gao Key Laboratory of Drug Targeting and Drug Delivery Systems West China School of PharmacySichuan University

Carbon nanomaterials,including graphene,carbon nanotubes,fullerene and fluorescent carbonaceous nanospheres（CDs）,have been extensively applied in many *** which,CDs have generated much excitement because of their unique optical and electronic properties,such as low photobleaching,no optical blinking,size-and composition-tunable fluorescence emission from visible to infrared wavelengths,large absorption coefficients across a broad spectral range and high levels of brightness and *** obtain CDs with high-quality,many methods were introduced and developed,including thermal/hydrothermal oxidation,electrochemical synthesis and microwave/ultrasonic synthesis[8].One-step hydrothermal/thermal treatment methods have been widely used for preparing CDs from various carbon materials,such as silk,juice,glucose or other synthetic ***,CDs have been explored in its various promising applications especially in biology and *** application of CDs has approached bio-imaging in tumor cells and tumor tissue,which was contributed to the photoluminescent characteristic of CDs and pathological property of *** to the quick amplification of tumor cells,there is a leaky vasculature in subcutaneous tumor with pore size of approximately 200 nm to 1.2μm,which was well-known as enhancedpermeability and retention *** CDs could passively target to these tumors by EPR effect which was benefited from their small particle ***,their application in non-invasive imaging of diseased tissues was restricted by the poor targeting efficiency of CDs due to the existence of biological barriers in *** glioma,the most aggressive and common intracranial tumor,is considered as the major cause of death from central nervous system *** blood brain barrier（BBB）restricts the transportation from blood vessels to brain,BBB is compromised in the glioma because of the quick growth of ***,the cutoff pore size of glioma is muc

关键词： fluorescent carbonaceous nanospheres RGD glioma non-invasive imaging

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Recent progress in drug delivery

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Acta Pharmaceutica Sinica B 2019年第6期9卷 1145-1162页

作者： Chong Li Jiancheng Wang Yiguang Wang huile gao Gang Wei Yongzhuo Huang Haijun Yu Yong Gan Yongjun Wang Lin Mei Huabing Chen Haiyan Hu Zhiping Zhang Yiguang Jin College of Pharmaceutical Sciences Southwest UniversityChongqing 400715China Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems State Key Laboratory of Natural and Biomimetic DrugsSchool of Pharmaceutical SciencesPeking UniversityBeijing 100191China Key Laboratory of Drug Targeting and Drug Delivery Systems West China School of PharmacySichuan UniversityChengdu 610041China Key Laboratory of Smart Drug Delivery Ministry of EducationFudan UniversityShanghai 201203China Shanghai Institute of Materia Medica Chinese Academy of SciencesShanghai 201203China School of Pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China School of Pharmaceutical Sciences(Shenzhen) Sun Yat-sen UniversityGuangzhou 510275China School of Radiation Medicine and Protection Soochow UniversitySuzhou 215123China School of Pharmaceutical Sciences Sun Yat-sen UniversityGuangzhou 510006China School of Pharmacy Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Pharmaceutical Sciences Beijing Institute of Radiation MedicineBeijing 100850China

Drug delivery systems(DDS)are defined as methods by which drugs are delivered to desired tissues,organs,cells and subcellular organs for drug release and absorption through a variety of drug *** usual purpose to improve the pharmacological activities of therapeutic drugs and to overcome problems such as limited solubility,drug aggregation,low bioavailability,poor biodistribution,lack of selectivity,or to reduce the side effects of therapeutic *** 2015-2018,significant progress in the research on drug delivery systems has been achieved along with advances in related fields,such as pharmaceutical sciences,material sciences and biomedical *** review provides a conciseoverview of current progress in this research area through its focus on the delivery strategies,construction techniques and specific *** is a valuable reference for pharmaceutical scientists who want to learn more about the design of drug delivery systems.

关键词： Pharmaceutics Drug delivery system Basic research Application Delivery strategy

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Acta Pharmaceutica Sinica B 2020年第6期10卷 946-946页

作者： Qingfeng Liu huile gao 不详

In vitro model is important for evaluation drug delivery systems,which can provide useful information quickly to optimize and evaluate the drug delivery *** is the first time that a differentiated M cell model is deve... 详细信息

关键词： al. nasal drug

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肿瘤微环境响应性纳米递药系统用于肿瘤免疫治疗的研究进展

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药学进展 2022年第7期46卷 485-494页

作者：胡川宋钰珺高会乐四川大学华西药学院靶向药物及释药系统教育部重点实验室

在过去的几十年里，癌症免疫治疗取得了巨大的进步，但不尽如人意的患者应答率及潜在的免疫相关不良事件仍是临床上的主要挑战。纳米递药系统在癌症治疗方面具有独特的优势。基于肿瘤微环境缺氧、弱酸性、蛋白酶异常表达等特点，研究者... 详细信息

在过去的几十年里，癌症免疫治疗取得了巨大的进步，但不尽如人意的患者应答率及潜在的免疫相关不良事件仍是临床上的主要挑战。纳米递药系统在癌症治疗方面具有独特的优势。基于肿瘤微环境缺氧、弱酸性、蛋白酶异常表达等特点，研究者们进一步设计了刺激响应性纳米递药系统，其已被广泛研究用于提高抗肿瘤免疫应答的效果和减少免疫相关的副作用。介绍了肿瘤微环境响应性纳米递药系统用于肿瘤免疫治疗的研究进展，并讨论了该类递药系统的应用前景和面临的挑战。

关键词：肿瘤微环境响应性递药系统肿瘤免疫疗法联合治疗

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溶酶体酸性微环境敏感型粒径可变纳米粒的构建及评价

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华西药学杂志 2017年第4期32卷 353-356页

作者：邰晓伟王蛘高会乐何勤四川大学华西药学院靶向药物与传递系统教育部重点实验室四川成都610041

目的构建一种以功能性支化聚乙烯亚胺(b PEI)为基本骨架材料的粒径可变纳米粒,用于递送药物至黑色素瘤的深部区域。方法通过酰胺键修饰特定量的琥珀酸酐至b PEI骨架上,得到具有电荷翻转功能的材料NSP,再引入聚N-异丙基丙烯酰胺(PNIPAM)... 详细信息

目的构建一种以功能性支化聚乙烯亚胺(b PEI)为基本骨架材料的粒径可变纳米粒,用于递送药物至黑色素瘤的深部区域。方法通过酰胺键修饰特定量的琥珀酸酐至b PEI骨架上,得到具有电荷翻转功能的材料NSP,再引入聚N-异丙基丙烯酰胺(PNIPAM)制备粒径可变纳米粒(PSP),分别考察其粒径、Zeta电位和释药行为;考察B16F10细胞对PSP的摄取及胞内内涵-溶酶体对PSP的影响;通过构建体外三维肿瘤球模型来考察纳米粒的穿透能力。结果载阿霉素粒径可变纳米粒(D/PSP)在p H7.4缓冲液中的粒径、PDI和Zeta电位分别为31.2±4.8 nm、0.106±0.015、-2.26±0.06 m V。在内涵-溶酶体所对应的p H5.0条件下,D/PSP的粒径可膨胀至891.6±26.3 nm,PDI为0.256±0.123,Zeta电位为15.61±0.19 m V。B16F10细胞对D/PSP的摄取在一定范围内呈孵育浓度依赖性及时间依赖性,其主要的入胞机制为网格蛋白介导和能量依赖型的内吞途径。结论成功制备了具有较好的溶酶体酸性微环境响应性的PSP,D/PSP具有较强的肿瘤球穿透能力。

关键词：粒径变化支化聚乙烯亚胺电荷翻转内涵-溶酶体溶酶体酸敏感阿霉素纳米粒黑色素瘤

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穿膜肽TAT修饰的自噬诱导肽Beclin 1抗肿瘤的初步研究

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华西药学杂志 2017年第2期32卷 163-166页

作者：余倩雯胡关莲王蛘高会乐何勤四川大学华西药学院成都四川610041

目的研究自噬诱导肽Beclin 1及其经穿膜肽TAT修饰后所得TAT-Beclin 1对乳腺癌的体外自噬诱导作用及体内外疗效。方法采用透射电子显微镜、eGFP-LC3细胞转染技术和蛋白免疫印迹法综合对比评价Beclin 1和TAT-Beclin 1对4T1细胞自噬流的影... 详细信息

目的研究自噬诱导肽Beclin 1及其经穿膜肽TAT修饰后所得TAT-Beclin 1对乳腺癌的体外自噬诱导作用及体内外疗效。方法采用透射电子显微镜、eGFP-LC3细胞转染技术和蛋白免疫印迹法综合对比评价Beclin 1和TAT-Beclin 1对4T1细胞自噬流的影响,通过体外细胞毒性和体内抑瘤实验评价其抗肿瘤疗效。结果 TAT-Beclin 1能显著提高Beclin 1在4T1细胞上的自噬诱导能力;TAT-Beclin 1在体内具有一定的抗4T1肿瘤能力。结论 TAT-Beclin 1较Beclin 1能更有效地诱导自噬并发挥治疗乳腺癌的效果。

关键词： TAT-Beclin 1 TAT 自噬诱导肽穿膜肽自噬流 4T1细胞凋亡乳腺癌

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