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

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

doi:10.3390/membranes11110818

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

Membranes (Basel). 2021 Oct 26;11(11):818. doi: 10.3390/membranes11110818.

Authors

Wen-Jyun Wang¹, Chung-Dann Kan², Chih-Yen Chen³, Yi-Yao Meng¹, Jieh-Neng Wang⁴, Wei-Ling Chen^{5

6}, Chia-Hsiang Chen¹, Wei-Peng Li^{1

7

8}

Affiliations

¹ Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
² Division of Cardiovascular Surgery, Department of Surgery National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan.
³ Department of Materials and Optoelectronic Science, National Sun Yat-Sen University, Kaohsiung 804, Taiwan.
⁴ Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan.
⁵ School of Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 110, Taiwan.
⁶ Institute Food and Drug Administration, Ministry of Health Welfare, Taipei 115, Taiwan.
⁷ Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.
⁸ Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan.

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.

Keywords: cancer; carbon monoxide; emulsion; microvesicles; poly(lactic-co-glycolic acid).