journal article·2018-10-23Open access

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

Wangxiao He, Jin Yan, Wei Jiang, Shichao Li, Yiping Qu, Fan Niu, Yuwei Yan, Fang Sui, Simeng Wang, Yi Zhou, Liang Jin, Yujun Li, Meiju Ji, Peter X. Ma, Min Liu, Wuyuan Lu, Peng Hou

Chemistry of Materials· Volume 30· Issue 20

Abstract

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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Research context

OpenAlex topics: Advanced biosensing and bioanalysis techniques · RNA Interference and Gene Delivery · Supramolecular Self-Assembly in Materials

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Center for Translational Medicine, Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China

Key Laboratory for Tumor Precision Medicine of Shaanxi Province and Department of Endocrinology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China

Institute of Human Virology and Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland 21201, United States

Department of Biologic and Materials Sciences, Department of Biomedical Engineering, Macromolecular Science and Engineering Center, Department of Materials Science and Engineering, University of Michigan, Ann Arbor, Michigan 48109, United States

Frontier Institute of Science and Technology, State Key Laboratory for Mechanical Behavior of Materials, Xi’an Jiaotong University, Xi’an 710049, China

Department of Infectious Diseases, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China

Center for Translational Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China

Funding

National Cancer Institute · China Scholarship Council · National Natural Science Foundation of China · First Affiliated Hospital, Xi’an Jiaotong University

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