Research on preparation and antitumor activity of redox-responsive polymer micelles co-loaded with sorafenib and curcumin

Abstract

A novel redox-responsive mPEG-SS-PLA (PSP) polymeric micelle was synthesized and prepared for the delivery of sorafenib (SAF) and curcumin (CUR). And a series of validations were conducted to confirm the structure of the synthesized polymer carriers. Using the Chou-Talalay approach, the combination indexes (CI) of SAF and CUR were determined, and explore the inhibitory effects of the two drugs on HepG2^R cells at different ratios. SAF/CUR-PSP polymeric micelles were prepared by thin film hydration method, and the physicochemical properties of nanomicelles were evaluated. The biocompatibility, cell uptake, cell migration, and cytotoxicity assays were assessed in HepG2^R cells. The expression of the phosphoinositol-3 kinase (PI3K)/serine/threonine kinase (Akt) signaling pathway was detected by Western blot assay. Additionally, the tumor suppressive effect of SAF/CUR-PSP micelles was clearly superior to free drug monotherapy or their physical combination in HepG2 cell-induced tumor xenografts. The current study revealed that mPEG-SS-PLA polymer micelles loaded with SAF and CUR showed the enhanced therapeutic effects against hepatocellular carcinoma in vitro and in vivo models. It has promising applications for cancer therapy.

GRAPHICAL ABSTRACT

Keywords:

• Sorafenib
• curcumin
• polymeric micelles
• redox-responsive
• hepatocellular carcinoma

Disclosure statement

The authors declared that they have no conflict of interest.

Data and code availability

The data that support the findings of this study are available on request from the corresponding author upon reasonable request.

Additional information

Funding

This research was funded by the Heilongjiang Postdoctoral Foundation (LBH-Z21214), the Provincial Undergraduate College Basal Research Foundation (2019-KYYWF-1342), the Doctor Scientific Research Startup Fund (JMSUBZ2019-14), the Heilongjiang Provincial Key Laboratory of New Drug Development, the Pharmacotoxicological Evaluation (KFKT2021-04), “the North Medicine and Functional Food Characteristic Subject Project in Heilongjiang Province (No. HLJTSXK-2022-03)” and “the Heilongjiang Provincial Higher Education Institutions Fundamental Research Fund for Excellent Innovative Team (2021-KYYWF-0637)” and the Natural Science Foundation of Heilongjiang Province of China (LH2022H095).