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Synergistic Therapy of a Naturally Inspired Glycopolymer-Based Biomimetic Nanomedicine Harnessing Tumor Genomic Instability.

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机构： [1]Huaxi MR Research Center (HMRRC), Department of Radiology, National Clinical Research Center for Geriatrics, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China. [2]West China Medical School, Sichuan University, Chengdu, 610041, China. [3]Functional and Molecular Imaging Key Laboratory of Sichuan Province, and Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, 610041, China. [4]Amgen Bioprocessing Centre, Keck Graduate Institute, Claremont, CA, 91711, USA.

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Inspired by natural saccharide-protein complexes, a stimuli-responsive biodegradable and branched glycopolymer-pyropheophorbide-a (Ppa) conjugate (BSP) with saccharide units for cancer therapy is constructed. A linear glycopolymeric conjugate (LSP), a branched glycopolymeric conjugate (BShP) from Ppa with long carbon chains, and a branched conjugate (BHSP) based on poly[N-(2-hydroxypropyl) methacrylamide] (polyHPMA) without saccharide units are prepared as controls. Through structure-activity relationship studies, BSP with a 3D network structure forms stable nanostructures via weak intermolecular interactions, regulating the stacking state of Ppa to improve the singlet oxygen quantum yield and the corresponding photodynamic therapy (PDT) effect. BSP shows high loading of olaparib, and are further coated with tumor cell membranes, resulting in a biomimetic nanomedicine (CM-BSPO). CM-BSPO shows highly efficient tumor targeting and cellular internalization properties. The engulfment of CM-BSPO accompanied with laser irradiation results in a prominent antitumor effect, evidenced by disruption of cell cycles in tumor cells, increased apoptosis and DNA damage, and subsequent inhibition of repair for damaged DNA. The mechanism for the synergistic effect from PDT and olaparib is unveiled at the genetic and protein level through transcriptome analysis. Overall, this biodegradable and branched glycopolymer-drug conjugate could be effectively optimized as a biomimetic nanomedicine for cancer therapy.© 2021 Wiley-VCH GmbH.

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出版当年[2021]版：

大类 | 1 区

材料科学

小类 | 1 区化学综合 1 区物理化学 1 区纳米科技 1 区材料科学：综合 1 区物理：应用 1 区物理：凝聚态物理

最新[2023]版：

大类 | 1 区

材料科学

小类 | 1 区化学：综合 1 区物理化学 1 区材料科学：综合 1 区纳米科技 1 区物理：应用 1 区物理：凝聚态物理

第一作者：

第一作者机构： [1]Huaxi MR Research Center (HMRRC), Department of Radiology, National Clinical Research Center for Geriatrics, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China. [2]West China Medical School, Sichuan University, Chengdu, 610041, China.

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通讯作者：

通讯机构： [1]Huaxi MR Research Center (HMRRC), Department of Radiology, National Clinical Research Center for Geriatrics, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China. [2]West China Medical School, Sichuan University, Chengdu, 610041, China. [3]Functional and Molecular Imaging Key Laboratory of Sichuan Province, and Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, 610041, China.

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