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

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

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Accurate tumor targeting,deep penetration and superb retention are still the main pursuit of developing excellent nanomedicine.To 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 iRGD.The 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 therapy.The loaded d-SN38 with disulfide bond responded to the high level of GSH in tumor cytoplasm,which conse-quently resulted in SN38 release and excellent chemo-photodynamic effect on tumor.In vitro,co-administering iRGD with d-SN38@NPs+laser showed higher cellular uptake,apoptosis ratio and multicellular spheroid penetration.In vivo,d-SN38@NPs/iRGD+laser displayed advanced penetration and accumulation in tumor,leading to 60.89％of tumor suppression in 4T1 tumor-bearing mouse model with a favorable toxicity profile.Our new strategy combining iRGD with structural transformable nano-particles greatly improves tumor targeting,penetrating and retention,and empowers anticancer efficacy.

Shape-transformableSN38 dimerGSH-responsiveChemo-photodynamic therapyiRGDCo-administrationCe6Breast cancer

Congcong Lin、Fan Tong、Rui Liu、Rou Xie、Ting Lei、Yuxiu Chen、Zhihang Yang、Huile Gao、Xiangrong Yu

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Department of Radiology,Zhuhai People's Hospital,Jinan University,Zhuhai 519000,China

Department of Medicinal Chemistry and Natural Medicine Chemistry,College of Pharmacy,Harbin Medical University,Harbin 150081,China

Key Laboratory of Drug Targeting and Drug Delivery Systems,West China School of Pharmacy,Sichuan University,Sichuan 610041,China

authors gratefully acknowledge the financial support from National Natural Science Foundation of Chinaauthors gratefully acknowledge the financial support from National Natural Science Foundation of ChinaResearch Funds of Sichuan Science and Technology DepartmentResearch Funds of Sichuan Science and Technology Department111 Project111 ProjectFundamental Research Funds for the Central Universities,and Natural Science Foundation of Hei-longjiang Province of China

Nos.819611380098207191519YYJC2250ChinaB18035ChinaYQ2019H004

2020

药学学报(英文版)

药学学报(英文版)

CSTPCDCSCDSCI
ISSN：
年,卷(期)：2020.10(12)
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