Peptide-Induced Self-Assembly of Therapeutics into a Well-Defined Nanoshell with Tumor-Triggered Shape and Charge Switch.
Peptide-Induced Self-Assembly of Therapeutics into a Well-Defined Nanoshell with Tumor-Triggered Shape and Charge Switch.
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DOI：
10.1021/acs.chemmater.8b02572
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Hou P
中科院分区：
文献类型：
--
作者：
He W;Yan J;Jiang W;Li S;Qu Y;Niu F;Yan Y;Sui F;Wang S;Zhou Y;Jin L;Li Y;Ji M;Ma PX;Liu M;Lu W;Hou P
大分子药物（>500 Da）如治疗性肽的肽调节自组装提供了改善可降解纳米材料的性质和生物功能的策略，但是大分子治疗剂递送的坚韧要求和缺乏对基于肽的自组装设计的理解为其应用提出了很高的障碍。在此，我们开发了一种新的策略，通过一个精心制作的肽，称为PSP（VVVVHHRGDC），能够直接与货物共轭成为PSP货物单体作为积木往往自组装成一个明确的纳米壳与肿瘤触发的形状和电荷开关的纳米工程大分子药物。作为概念的证明，将PSP与称为DPMI（1492.5Da）的肿瘤抑制剂p53的D-肽激活剂缀合产生直径约80 nm的称为PSP-DPMI的中空球，其仅在肿瘤组织的酸性微环境中崩解，随后是整合素介导的PSP-DPMI单体的细胞摄取。重要的是，基于PSP的自组装成功地赋予DPMI长循环时间和高癌细胞特异性细胞内积累。PSP-DPMI纳米壳通过p53恢复在体外和体内有效地抑制肿瘤生长，同时保持高度有利的体内安全性特征。在传统的封装和缀合之外，我们的研究展示了一种临床上可行的新方法，用于纳米工程大分子药物，如用于抗癌治疗的肽，并为治疗诊断学递送提供了一种无危害的替代策略。
Peptide-tuned self-assembly of macromolecular agents (>500 Da) such as therapeutic peptides offers a strategy to improve the properties and biofunctions of degradable nanomaterials, but the tough requirement of macromolecular therapeutics delivery and a lack of understanding of peptide-based self-assembly design present high barriers for their applications. Herein, we developed a new strategy for nanoengineering macromolecular drugs by an elaborate peptide, termed PSP (VVVVVHHRGDC), capable of directly conjugating with cargo to be a PSP-cargo monomer as building block tending to self-assemble into a well-defined nanoshell with tumor-triggered shape and charge switch. As a proof of concept, conjugation PSP to a D-peptide activator of tumor suppressor p53 termed DPMI (1492.5 Da) generated hollow spheres ~80 nm in diameter named PSP-DPMI that disintegrated only in the acidic microenvironment of tumor tissues, followed by integrin-mediated cellular uptake of PSP-DPMI monomers. Importantly, PSP-based self-assembly successfully endowed the DPMI with long circulation time and high cancer-cell-specific intracellular accumulation. PSP-DPMI nanoshells potently inhibited tumor growth in vitro and in vivo by the p53 restoration, while maintaining a highly favorable in vivo safety profile. Out of conventional encapsulation and conjugation, our study showcases a clinically viable novel method to nanoengineer macromolecular agents such as peptide for anticancer therapy and provides a hazard-free alternative strategy for the theranostics delivery.
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MDM2/X 靶向治疗的临床概述。
影响因子：
4.7
作者：
Burgess A;Chia KM;Haupt S;Thomas D;Haupt Y;Lim E
通讯作者：
Lim E
影响因子：
56.9
作者：
Bunz, F;Dutriaux, A;Vogelstein, B
通讯作者：
Vogelstein, B
DOI：
10.1016/0277-5379(83)90418-2
发表时间：
1983-01-01
期刊：
EUROPEAN JOURNAL OF CANCER & CLINICAL ONCOLOGY
影响因子：
--
作者：
COATES, A;ABRAHAM, S;TATTERSALL, MHN
通讯作者：
TATTERSALL, MHN
影响因子：
64.8
作者：
King, Neil P.;Bale, Jacob B.;Sheffler, William;McNamara, Dan E.;Gonen, Shane;Gonen, Tamir;Yeates, Todd O.;Baker, David
通讯作者：
Baker, David
影响因子：
38.3
作者：
通讯作者：
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