An artificial "closed-loop" system that mimics the glucose-responsive insulin secretion of pancreas β-cells can potentially improve the treatment efficacy for diabetes. Herein, a lipid bilayer-coated polymeric nanoparticle (NP) with "core-shell" structure is designed. As far as it is known, it is the first and only intravenous nanoplatform utilizing enzymatic-oxidation scheme to achieve glucose-responsive insulin delivery so far. Ethoxy acetal-derivatized dextran nanoparticles (Ace-DEX NPs) are constructed as "inner core" loaded with insulin, and coloading glucose oxidase (GOx) and catalase (CAT) endow the "inner core" excellent glucose-sensitive ability. Red blood cell membrane (RBCm)-derived coating is adopted as "outer shell." It collectively provides a closed microenvironment for GOx-based enzymatic-oxidation scheme and camouflages it from elimination. Above all, the anchored glucose transporters (GLUTs) on the "outer shell" are able to sense blood glucose levels and facilitate the transport of outer blood glucose getting inside. Under a hyperglycemic condition, the internalized glucose is catalytically converted into gluconic acid with the aid of the GOx and subsequently triggers acid degradation of the "inner core" to secrete insulin. By governing the blood glucose levels on an automatic and continuous basis, the RBCm-Ace-DEX NPs can effectively respond to hyperglycemia and turn to resting conditions under normoglycemia.
Prostate cancer, one of the leading causes of disease and death in men all over the world, is challenging to treat. α-Enolase, a multifunctional protein, is overexpressed on human prostate carcinoma cells, and thereby it is a potential target for treatment of prostate cancer. In the current study, the pHCT74 peptide was used to construct a kind of highly targeted liposome (pHCT74-lipo) loaded with doxorubicin (pHCT74-lipo-Dox), which specifically targeted α-enolase on prostate tumour cells. Compared with liposomes without pHCT74 modification, pHCT74-lipo-Dox displayed a superior intracellular internalization with enhanced tumour cytotoxicity. In the in vivo study, pHCT74-lipo showed much higher tumour accumulation. In addition, loaded into pHCT74-lipo, doxorubicin demonstrated significantly improved anti-tumour activity on prostate tumour-bearing mice. These results suggest that the pHCT74 peptide has potential to be used in the development of a novel drug delivery system for targeted therapy against prostate cancer.
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