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Self-Stabilized Supramolecular Assemblies Constructed from PEGylated Dendritic Peptide Conjugate for Augmenting Tumor Retention and Therapy.

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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]National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610064, China. [3]Animal Experimental Center of West China Hospital, Core Facility of West China Hospital, Sichuan University, Chengdu, 610041, China. [4]West China School of Medicine, West China College of Stomatology, Sichuan University, Chengdu, 610041, China. [5]Amgen Bioprocessing Centre, Keck Graduate Institute, Claremont, CA, 91711, USA. [6]Functional and Molecular Imaging Key Laboratory of Sichuan Province, Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, 610041, China.
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关键词: colloidal stability dendritic peptides dissipative particle dynamics simulations polymeric conjugates supramolecular assembly transcriptome

摘要:
Supramolecular self-assemblies of dendritic peptides with well-organized nanostructures have great potential as multifunctional biomaterials, yet the complex self-assembly mechanism hampers their wide exploration. Herein, a self-stabilized supramolecular assembly (SSA) constructed from a PEGylated dendritic peptide conjugate (PEG-dendritic peptide-pyropheophorbide a, PDPP), for augmenting tumor retention and therapy, is reported. The supramolecular self-assembly process of PDPP is concentration-dependent with multiple morphologies. By tailoring the concentration of PDPP, the supramolecular self-assembly is driven by noncovalent interactions to form a variety of SSAs (unimolecular micelles, oligomeric aggregates, and multi-aggregates) with different sizes from nanometer to micrometer. SSAs at 100 nm with a spherical shape possess extremely high stability to prolong blood circulation about 4.8-fold higher than pyropheophorbide a (Ppa), and enhance tumor retention about eight-fold higher than Ppa on day 5 after injection, which leads to greatly boosting the in vivo photodynamic therapeutic efficiency. RNA-seq demonstrates that these effects of SSAs are related to the inhibition of MET-PI3K-Akt pathway. Overall, the supramolecular self-assembly mechanism for the synthetic PEGylated dendritic peptide conjugate sheds new light on the development of supramolecular assemblies for tumor therapy.© 2021 The Authors. Advanced Science published by 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 纳米科技 1 区 材料科学:综合 2 区 化学综合
最新[2023]版:
大类 | 1 区 材料科学
小类 | 1 区 化学:综合 1 区 材料科学:综合 2 区 纳米科技
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]National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610064, China.
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]National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610064, China. [6]Functional and Molecular Imaging Key Laboratory of Sichuan Province, Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, 610041, China.
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