pH low insertion peptide (pHLIP)-decorated polymeric nanovehicle for efficient and pH-responsive siRNA translocation

Guo-Bin Ding; Xiaohui Ma; Xue Meng; Peng Yang; Roland H. Stauber; Zhuoyu Li

Materials & Design (Dec 2021)

pH low insertion peptide (pHLIP)-decorated polymeric nanovehicle for efficient and pH-responsive siRNA translocation

Guo-Bin Ding,
Xiaohui Ma,
Xue Meng,
Peng Yang,
Roland H. Stauber,
Zhuoyu Li

Affiliations

Guo-Bin Ding: Institute of Biotechnology, the Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan 030006, China; Corresponding authors at: Institute of Biotechnology, the Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan 030006, China, Nanobiomedicine Department/ENT, University Medical Center Mainz, Mainz 55131, Germany
Xiaohui Ma: Institute of Biotechnology, the Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan 030006, China
Xue Meng: Institute of Biotechnology, the Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan 030006, China
Peng Yang: Institute of Biotechnology, the Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan 030006, China
Roland H. Stauber: Institute of Biotechnology, the Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan 030006, China; Nanobiomedicine Department/ENT, University Medical Center Mainz, Mainz 55131, Germany; Corresponding authors at: Institute of Biotechnology, the Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan 030006, China, Nanobiomedicine Department/ENT, University Medical Center Mainz, Mainz 55131, Germany
Zhuoyu Li: Institute of Biotechnology, the Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan 030006, China; Corresponding authors at: Institute of Biotechnology, the Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan 030006, China, Nanobiomedicine Department/ENT, University Medical Center Mainz, Mainz 55131, Germany

Journal volume & issue: Vol. 212
p. 110197

Abstract

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As a hallmark of most solid tumors, tumor acidic microenvironment aids tumor survival and progression. Tumor acidity also represents a tumor-specific stimulus that has been harnessed for the design and development of pH-responsive drug delivery systems. Pyruvate kinase M2 (PKM2) functions as an oncoprotein in tumorigenesis, and its overexpression in many tumors promotes metabolic rewiring towards aerobic glycolysis. Herein, a pH low insertion peptide (pHLIP)-functionalized copolymer of polyethylenimine and polylactide (pHLIP-PEI-PLA) was synthesized and self-assembled into a pH-responsive nanovehicle for delivery of siRNA to specifically target PKM2, a rate-limiting enzyme in glycolysis. The delivery of siPKM2 by pHLIP-decorated polymeric nanovehicle sufficiently downregulated the expression of PKM2 and exhibited potent inhibition on HepG2 cell migration. We believe that this strategy of targeting glycolysis-associated PKM2 gene by tumor acidity-responsive RNAi nanovehicle may offer a potential means for anticancer therapy.

Published in Materials & Design

ISSN: 0264-1275 (Print); 1873-4197 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Technology: Electrical engineering. Electronics. Nuclear engineering: Materials of engineering and construction. Mechanics of materials
Website: https://www.journals.elsevier.com/materials-and-design

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