Tumor-Targeted Radioiodinated Glyconanoparticles for Doxorubicin Delivery and Auger-Chemotherapy in Triple-Negative Breast Cancer.

ABSTRACT: This study focuses on developing a tumor-responsive core-shell glyconanoparticle formulation targeting galectin-3 (Gal-3) in triple-negative breast cancer (TNBC) for Auger-chemotherapy. The formulation utilizes citrus pectin dialdehyde (CPDA) to create nanoparticles capable of tumor-responsive release of the drug Doxorubicin (Dox) for chemotherapy and incorporating the radionuclide, Iodine-125 for Auger therapy. CPDA-based core-shell nanoparticles (CPDANP) are engineered for drug Dox release in the tumor microenvironment using boronate ester links between polymeric chains of CPDANP and imine linkages for conjugating Dox to CPDANP (CPDANP-Dox). The nanoparticles are characterized for their size, effective charge, and core-shell like structure by DLS and TEM and radiolabeled with ¹²⁵I. Gal-3 specific targeting of CPDANP-Dox and ¹²⁵I to the nucleus of tumor cells is confirmed by fluorescence microscopy and estimating radioactivity in the isolated nucleus of cells. In vitro and in vivo studies demonstrated that the combination therapy with [¹²⁵I] I-CPDANP-Dox exhibited enhanced cytotoxicity in TNBC cells. SPECT imaging and biodistribution studies showed rapid clearance of the formulations from the bloodstream, and tumor regression studies in 4T1 tumor-bearing mice confirmed the therapeutic superiority of the combined treatment over individual therapies. This study highlights the potential of CPDANP as a dual-targeting platform for efficient Auger-chemo therapy in the treatment of TNBC.

SUBMITTER: Suman SK 

PROVIDER: S-EPMC12366269 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature