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    张楠等Combining Fruquintinib and Doxorubicin in Size-Converted NanoDrug Carriers for Tumor Therapy

    2022-12-13   点击:[]

    Combining Fruquintinib and Doxorubicin in Size-Converted NanoDrug Carriers for Tumor Therapy

    【作者】Nan Zhang, Xiangying Xin, Nannan Feng, Deqiao Wu, Junwei Zhang, Tong Yu, Qianqian Jiang, Ming Gao, Hui Yang, Siyuan Zhao, Qingfeng Tian, and Zhenzhong Zhang

    【期刊名】ACS Biomater. Sci. Eng.

    【影响因子】 5.395

    【作者单位】 School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, PR China


    【年,卷():页码】2022, 8, 1907−1920

    【关键词】 fruquintinib, fruquintinib-combined chemotherapy, PAMAM, tumor tissue penetration, size-converted

    【摘要】 Single-modality tumor therapy confronts many challenges, such as incomplete tumor ablation, tumor metastasis, and limited tumor tissue penetration. Combination therapy simultaneously achieves deep drug delivery to fully exert synergistic effects and has received increasing attention. Herein, based on the excellent efficacy of anti-angiogenesis therapy combined with chemotherapy and the specific size of the poly-amidoamine dendrimer (PAMAM), we developed a pH-triggered size-converted nano-drug delivery system to co-deliver fruquintinib (FRU) and doxorubicin (DOX). This study used cyclic Arg-Gly-Asp (cRGD) as the target, pH-responsive liposomes (PRLs), and PAMAM as the drug carrier. The FRU and DOX-loaded small-particle-size complex polyamide-amine-doxorubicin (PD) was encapsulated into PRLs with the target to construct a size-converted nano-drug delivery system, PRL-PD/FRU-cRGD. This nanoparticle (∼120 nm) actively targeted tumor tissues and used the acidic microenvironment outside tumor cells to release FRU and small-particle-size complex PD (∼15 nm), enabling the conversion of large-size nanoparticles to small-size nanoparticles and resulting in efficient tumor accumulation. In addition, the released PD could realize the deep delivery of DOX, showing efficient deep tumor penetration and further enhancing the tumor-suppressing effect. The results of in vivo and in vitro experiments showed that PRL-PD/FRU-cRGD exhibited the excellent synergistic effects of anti-angiogenesis therapy combined with chemotherapy and effectively inhibited tumor cell proliferation and metastasis, thereby achieving efficient tumor therapy. Thus, PRL-PD/FRU-cRGD shows great potential for combined tumor therapy.


    【全文链接】

    https://doi.org/10.1021/acsbiomaterials.1c01606


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