Gene

Cell biology

Biology

Glycolysis

Materials science

Peptide

Anaerobic glycolysis

Pyruvate kinase

Cancer research

Biochemistry

Small interfering RNA

Transfection

Polyethylenimine

Drug delivery

Nanotechnology

Organic chemistry

Enzyme

Tumor microenvironment

Tumor cells

PKM2

Chemistry

Biophysics

Materials & Design

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.

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