Novel micelle formulation of curcumin for enhancing antitumor activity and inhibiting colorectal cancer stem cells

Ke Wang,¹ Tao Zhang,¹ Lina Liu,² Xiaolei Wang,¹ Ping Wu,¹ Zhigang Chen,¹ Chao Ni,¹ Junshu Zhang,¹ Fuqiang Hu,⁴ Jian Huang<sup>1,3

1</sup>Cancer Institute, ²Department of Pharmacy, Second Affiliated Hospital (Binjiang Branch), ³Department of Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, ⁴College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China

Background and methods: Curcumin has extraordinary anticancer properties but has limited use due to its insolubility in water and instability, which leads to low systemic bioavailability. We have developed a novel nanoparticulate formulation of curcumin encapsulated in stearic acid-g-chitosan oligosaccharide (CSO-SA) polymeric micelles to overcome these hurdles.
Results: The synthesized CSO-SA copolymer was able to self-assemble to form nanoscale micelles in aqueous medium. The mean diameter of the curcumin-loaded CSO-SA micelles was 114.7 nm and their mean surface potential was 18.5 mV. Curcumin-loaded CSO-SA micelles showed excellent internalization ability that increased curcumin accumulation in cancer cells. Curcumin-loaded CSO-SA micelles also had potent antiproliferative effects on primary colorectal cancer cells in vitro, resulting in about 6-fold greater inhibition compared with cells treated with a solution containing an equivalent concentration of free curcumin. Intravenous administration of curcumin-loaded CSO-SA micelles marginally suppressed tumor growth but did not increase cytotoxicity to mice, as confirmed by no change in body weight. Most importantly, curcumin-loaded CSO-SA micelles were effective for inhibiting subpopulations of CD44⁺/CD24⁺ cells (putative colorectal cancer stem cell markers) both in vitro and in vivo.
Conclusion: The present study identifies an effective and safe means of using curcumin-loaded CSO-SA micelles for cancer therapy.

Keywords: chitosan oligosaccharide, polymeric micelle, curcumin, drug delivery, colorectal cancer, cancer stem cells