Peptide-Induced Self-Assembly of Therapeutics into a Well-Defined Nanoshell with Tumor-Triggered Shape and Charge Switch

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...

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Veröffentlicht in:Chemistry of materials : a publication of the American Chemical Society. - 1998. - 30(2018), 20 vom: 01., Seite 7034-7046
1. Verfasser: He, Wangxiao (VerfasserIn)
Weitere Verfasser: Yan, Jin, Jiang, Wei, Li, Shichao, Qu, Yiping, Niu, Fan, Yan, Yuwei, Sui, Fang, Wang, Simeng, Zhou, Yi, Jin, Liang, Li, Yujun, Ji, Meiju, Ma, Peter X, Liu, Min, Lu, Wuyuan, Hou, Peng
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2018
Zugriff auf das übergeordnete Werk:Chemistry of materials : a publication of the American Chemical Society
Schlagworte:Journal Article
Beschreibung
Zusammenfassung: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
Beschreibung:Date Revised 29.03.2024
published: Print-Electronic
Citation Status PubMed-not-MEDLINE
ISSN:0897-4756
DOI:10.1021/acs.chemmater.8b02572