Design of GSH-Responsive Curcumin Nanomicelles for Oesophageal Cancer Therapy

Zhaoming Ma; Xuzhu Gao; Faisal Raza; Hajra Zafar; Guanhong Huang; Yunyun Yang; Feng Shi; Deqiang Wang; Xia He

doi:10.3390/pharmaceutics14091802

Design of GSH-Responsive Curcumin Nanomicelles for Oesophageal Cancer Therapy

Pharmaceutics. 2022 Aug 27;14(9):1802. doi: 10.3390/pharmaceutics14091802.

Authors

Zhaoming Ma^{1

2}, Xuzhu Gao¹, Faisal Raza³, Hajra Zafar³, Guanhong Huang¹, Yunyun Yang¹, Feng Shi⁴, Deqiang Wang^{4

5}, Xia He²

Affiliations

¹ Department of Radiotherapy, The Second People's Hospital of Lianyungang, Lianyungang 222023, China.
² Department of Radiation Oncology, Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing 210009, China.
³ School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
⁴ Institute of Digestive Diseases, Jiangsu University, Zhenjiang 212001, China.
⁵ Department of Medical Oncology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, China.

Abstract

Oesophageal cancer is a malignant tumor with high morbidity and mortality. Surgical treatment, radiotherapy, and chemotherapy are the most common treatment methods for oesophageal cancer. However, traditional chemotherapy drugs have poor targeting performance and cause serious adverse drug reactions. In this study, a GSH-sensitive material, ATRA-SS-HA, was developed and self-assembled with curcumin, a natural polyphenol antitumor drug, into nanomicelles Cur@ATRA-SS-HA. The micelles had a suitable particle size, excellent drug loading, encapsulation rate, stability, biocompatibility, and stable release behaviour. In the tumor microenvironment, GSH induced disulfide bond rupture in Cur@ATRA-SS-HA and promoted the release of curcumin, improving tumor targeting. Following GSH-induced release, the curcumin IC50 value was significantly lower than that of free curcumin and better than that of 5-FU. In vivo pharmacokinetic experiments showed that the drug-loaded nanomicelles exhibited better metabolic behaviour than free drugs, which greatly increased the blood concentration of curcumin and increased the half-life of the drug. The design of the nanomicelle provides a novel clinical treatment for oesophageal cancer.

Keywords: GSH responsive; curcumin; nanomicelles; oesophageal cancer.

Grants and funding

This work was supported by grants from the High-level Innovation and Entrepreneurship Talents Introduction Program of Jiangsu Province of China [grant number 2019-30345]; The “521 Project” scientific research funding project of Lianyungang City [grant number LYG06521202157].