Preparation of a PEGylated liposome that co-encapsulates L-arginine and doxorubicin to achieve a synergistic anticancer effect

Haitao Feng; Jeong-Hun Kang; Song Qi; Akihiro Kishimura; Takeshi Mori; Yoshiki Katayama

doi:10.1039/D1RA06514A

Preparation of a PEGylated liposome that co-encapsulates l-arginine and doxorubicin to achieve a synergistic anticancer effect†

Haitao Feng,^a Jeong-Hun Kang,^b Song Qi,

^c Akihiro Kishimura,

^acde Takeshi Mori

*^acef and Yoshiki Katayama

*^acdefg

Author affiliations

* Corresponding authors

^a Department of Applied Chemistry, Graduate School of Engineering, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan

^b Division of Biopharmaceutics and Pharmacokinetics, National Cerebral and Cardiovascular Center Research Institute, 6-1 Shinmachi, Kishibe, Suita, Osaka 564-8565, Japan

^c Graduate School of Systems Life Sciences, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan

^d Center for Future Chemistry, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan

^e International Research Center for Molecular Systems, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan

^f Centre for Advanced Medicine Innovation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Japan

^g Department of Biomedical Engineering, Chung Yuan Christian University, 200 Chung Pei Rd., Chung Li, Taiwan

Abstract

Strategies that combine chemotherapies with unconventional agents such as nitric oxide (NO) have been shown to enhance cancer therapies. Compared with small molecule chemotherapy drugs, nanosized particles have improved therapeutic efficacies and reduced systemic side effects because of the enhanced permeability and retention effect. In this report, we prepared PEGylated liposomes (LP) that incorporated L-arginine (Arg) and the anticancer drug doxorubicin (Dox) to yield a co-delivery system (Dox–Arg-LP). On the basis of our previous research, we hypothesized that Dox–Arg-LP should achieve a synergistic anticancer effect because Arg conversion to NO by activated M1 macrophages augments the chemotherapeutic activity of Dox. Dox–Arg-LP showed comparable physical properties to those of conventional Dox-only liposomes (Dox-LP). In vitro assessment revealed that the cytotoxicity of Dox–Arg-LP toward cancer cells was significantly higher than that of Dox-LP. In vivo application of Dox–Arg-LP in mice enhanced the chemotherapeutic effect with a 2 mg kg⁻¹ dose of Dox–Arg-LP achieving the same therapeutic efficacy as a two-fold higher dose of Dox-LP (i.e., 4 mg kg⁻¹). Therefore, co-encapsulation of dual agents into a liposome formulation is an efficient strategy to enhance chemotherapy while reducing systemic toxicity.

RSC Advances

Preparation of a PEGylated liposome that co-encapsulates l-arginine and doxorubicin to achieve a synergistic anticancer effect†

Abstract

Supplementary files

Article information

Download Citation

Permissions

Preparation of a PEGylated liposome that co-encapsulates L-arginine and doxorubicin to achieve a synergistic anticancer effect

Social activity

Search articles by author

Spotlight

Advertisements