Hyaluronan Reduces Cationic Liposome-Induced Toxicity and Enhances the Antitumor Effect of Targeted Gene Delivery in Mice.

ACS Applied Materials & Interfaces
Yanping QianXiawei Wei

Abstract

Cationic nanocarriers are reported to induce cell necrosis, especially in the lungs upon systemic administration. The release of damage-associated molecular patterns, such as mitochondrial DNA from the injured cell may result in the inflammatory toxicity of the nanocarrier, which has largely limited its clinical application. Partial blocking of the surface charge of cationic nanocarriers might improve their safety. As hyaluronan (HA) is an anionic polysaccharide that is widely used for specific binding to CD44 to improve the cellular uptake efficiency in tumor-targeting therapy, in this study, we modified cationic liposomes (LP) with the negatively charged HA at a mass ratio of 10% to prepare targeted HA-modified cationic liposomes (HALP). Cationic liposomes modified with hyaluronan showed significantly less cytotoxicity due to the blockage of their surface charge than the unmodified liposomes. In addition, HA modification helped to reduce cell necrosis in lung tissue and reduced the amount of mitochondria subsequently released, which alleviated pulmonary inflammation in mice. HA-modified liposomes also improved the survival of mice injected with a fatal dose of HALP compared with mice injected with cationic LP. In addition, bo...Continue Reading

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Citations

Jul 28, 2020·Nanomaterials·Chunhua Yang, Didier Merlin
Mar 4, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Duopeng AnMeiqing Feng
Jul 31, 2020·Nanomedicine : Nanotechnology, Biology, and Medicine·Wenjun WangHuiling Hu
Jun 4, 2021·The AAPS Journal·Amanda Catalina Ramirez-Phillips, Dexi Liu
Jul 3, 2021·Langmuir : the ACS Journal of Surfaces and Colloids·Martina HavlíkováFilip Mravec

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