Polymerized Polyphenol-Decorated Cationic Hydroxyethylcellulose Nanocomplexes for Enhanced Breast Cancer Cell Killing Effects

In this study, epigallocatechin gallate (EG)-containing multifunctional nanocomplexes based on cationic hydroxyethyl cellulose (HEC) were developed for breast cancer–targeted drug/gene codelivery. The pPBA-EG polymer was synthesized by grafting EG–phenylboronic acid (PBA) conjugates onto a poly(methyl vinyl ether-alt-maleic anhydride) (pMVMA) backbone, and combined with polyethylenimine 2k–modified hydroxyethyl cellulose (HECP2k) to deliver doxorubicin (Dox) and Bcl-2 siRNA, maintaining high transfection efficiency while enhancing EG stability and functionality. The resulting pPBA-EG/HECP2k@Dox/siRNA nanocomplexes exhibited suitable nanoscale size, positive surface charge, and efficient nucleic acid condensation. Enhanced cellular uptake via sialic acid interactions of the nanocomplexes was observed in MDA-MB-231 cells, leading to strong anticancer effects even in Dox-resistant cancer cells. Significant Bcl-2 downregulation and FAS upregulation indicated apoptosis-mediated cell death. These findings suggest that pPBA-EG/HECP2k@Dox/siRNA nanocomplexes present a promising strategy for concurrent delivery of siRNA, Dox, and EG, enhancing therapeutic potential against sialic acid-overexpressing breast cancer.