Synthetic Poly(lactic-co-glycolic Acid) Microvesicles as a Feasible Carbon Monoxide-Releasing Platform for Cancer Treatment.

Wen-Jyun Wang,Chih-Yen Chen,Chia-Hsiang Chen,Yi-Yao Meng,Wei-Ling Chen,Chung-Dann Kan,Wei-Peng Li,Jieh-Neng Wang

doi:10.3390/membranes11110818

Abstract

Biogenic microvesicles (MVs) play a pivotal role in intercellular signal communication, thus initiating critical biological responses such as the proliferation of cancer cells, gene and protein transport, and chemo-drug resistance. In addition, they have been recognized as having great potential in drug delivery applications. However, the productivity of biologically produced MVs is not sufficient for clinical applications. In this study, synthetic poly(lactic-co-glycolic acid) (PLGA) MVs were prepared via a double emulsion method. The PLGA MVs had a biogenic MV-mimic vesicular structure with a hydrophilic core/surface and hydrophobic interior of the shell, showing great potential for drug delivery. We successfully embedded hydrophobic iron carbonyl (IC), a carbon monoxide (CO) donor, in the PLGA shell region, enabling the delivery of IC in an aqueous solution. Because of the intrinsic properties of PLGA, it was susceptible to temperature, and the MVs could easily collapse in a warm environment, leading to the decomposition of IC into CO. The in vitro result indicated that the cell viability of A549 lung carcinoma cells significantly decreased to 14% after treatment with IC-loaded PLGA MVs for 24 h, suggesting that these synthetic PLGA MVs constitute an excellent drug delivery platform.

Highlights

Extracellular vesicles (EVs) are biological nanoparticles secreted by mammalian cells, bacteria, and fungus under specific conditions or environments [1,2,3]
Our artificial MVs showed an excellent ability to carry unstable iron-based complexes and revealed significant cytotoxicity to lung cancer cells through spontaneous iron carbonyl (IC) decomposition into carbon monoxide (CO) at 37 ◦C and ensuing CO-related mitochondria exhaustion. This result indicates that poly(lactic-co-glycolic acid) (PLGA) MVs with cell membrane-mimic shells represent a suitable carrier for water-insoluble drug delivery
A synthetic approach for preparing MVs is more feasible for achieving a reasonable yield for clinical requirements than biogenic methods

Summary

Introduction

Extracellular vesicles (EVs) are biological nanoparticles secreted by mammalian cells, bacteria, and fungus under specific conditions or environments [1,2,3]. The main objective of secreting these EVs is to communicate between individual cells through the signaling genes or proteins delivery, regulating cellular processes such as tumor metastasis, gene transport, defense, infection, quorum sensing, and autophagy [6,7,8,9]. Based on this principle, MVs and OMVs have been indicated to have great potential as carriers to transport drugs into specific cancer cells; many scientists have performed related research on identifying vesicle types, exploring the mechanism of EV secretion, and developing the methodology of vesicle generation [10,11,12]. Developing a feasible method with the ideal productivity of vesicles remains a great challenge that it is essential to overcome

Methods

Results

Conclusion