Abstract 6395: Enhanced antitumor efficacy of berbamine dihydrochloride nanomedicine via apoptosis induction in colorectal cancer.

Abstract Background: Berbamine dihydrochloride (BBM), a natural bisbenzylisoquinoline alkaloid, exhibits broad antitumor activity. However, its clinical translation is hampered by nonspecific tissue distribution, poor bioavailability, and dose-limiting toxicity. Bovine serum albumin (BSA) nanoparticles represent an ideal drug delivery platform because of their biocompatibility, low immunogenicity, and inherent tumor-targeting capability. This study aimed to develop BBM-loaded BSA nanoparticles (BBM-BSA-NPs) to enhance drug targeting and antitumor efficacy against colorectal cancer (CRC). Methods: BBM-BSA-NPs were prepared and characterized. In vitro cytotoxicity was assessed against CRC cell lines (CT26, HT29) and other cancer lines (AGS, CAOV3, HepG2) via CCK-8 assays. Selectivity was evaluated by comparing the effects on cancer cells with those on normal 293 cells. Apoptosis induction was measured by flow cytometry. In vivo antitumor efficacy and systemic safety were investigated in a murine CT26 tumor model. Results: Compared with native BBM, BBM-BSA-NPs significantly increased the cytotoxicity to CT26 and HT29 cells in a concentration- and time-dependent manner (P < 0.05). The formulation showed selective toxicity toward cancer cells, with markedly greater inhibition in HepG2 cells (P < 0.05) and minimal effects on normal 293 cells at 24 h and 48 h. Notably, BBM-BSA-NPs effectively induced morphological changes and apoptosis in CT26 cells, with apoptosis rates significantly exceeding those of native BBM at all concentrations tested (P < 0.05). In vivo, BBM-BSA-NP treatment resulted in a remarkable reduction in tumor volume (279.19 ± 46.75 mm3) and weight (0.13 ± 0.04 g), significantly outperforming native BBM (456.75 ± 54.64 mm3; 0.29 ± 0.04 g; P < 0.05). No significant changes in body weight or systemic toxicity were observed, confirming the safety of the treatment. The blank BSA-NPs showed no antitumor activity, confirming that the efficacy and safety benefits were attributable to the nanoformulation. Conclusion: We successfully developed a novel BBM-BSA nanoparticle system that significantly enhances the selective cytotoxicity and apoptotic induction of BBM against colorectal cancer while improving its therapeutic efficacy in vivo. This study provides a compelling rationale for leveraging albumin nanoparticles to repurpose BBM as a potent and safe therapeutic agent for CRC. Citation Format: Chan Zhang, Qiutong Guan, Zhenhua Li, . Enhanced antitumor efficacy of berbamine dihydrochloride nanomedicine via apoptosis induction in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6395.