Self-assembled nanocomposites of carboxymethyl β-dextran/protamine sulfate for enhanced chemotherapeutic drug sensitivity of triple-negative breast cancer by autophagy inhibition via a ternary collaborative strategy

In this study, a tri-drug nanocomposite (NP) delivery system was devised using carboxymethyl β-dextran (CMD) and protamine sulfate (PS), two natural materials with good bio-compatibility. They were designed to carry the chemotherapeutic drug docetaxel (DTX), the autophagy inhibitor chloroquine (CQ), and Atg5 siRNA to cancer cells. The CQ + DTX + Atg5 siRNA NPs was driven by electrostatic interaction and self-assembly methods. The breast cancer cell line MDA-MB-231 was used for both cell culture and establishing mouse xenograft model. Our findings demonstrated that CQ and Atg5 siRNA encapsulated in NPs could enhance the sensitivity of tumor cells to DTX. The NPs exhibited remarkable considerable therapeutic effects for treating triple-negative breast cancer (TNBC) and good biosafety. Therefore, we established a novel multifunctional nanoplatform based on CMD and PS that enhances chemotherapeutic drug sensitivity through an autophagy inhibition strategy, providing new opportunities to overcome conventional drug resistance and enhance therapeutic efficiency against TNBC.PMID:36780963 | DOI:10.1016/j.ijbiomac.2023.123663
Source: International Journal of Biological Macromolecules - Category: Biochemistry Authors: Source Type: research