Suman Shishu Kant, Balakrishnan Biji, Mallia Madhava B, Mukherjee Archana
Radiopharmaceuticals Division, Bhabha Atomic Research Centre (BARC), Mumbai, 400085, India.
Homi Bhabha National Institute, Anushaktinagar, Mumbai, 400094, India.
Small. 2025 Aug;21(32):e2502419. doi: 10.1002/smll.202502419. Epub 2025 Jun 23.
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 I. Gal-3 specific targeting of CPDANP-Dox and I 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 [I] 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.
本研究聚焦于开发一种肿瘤响应性核壳聚糖纳米颗粒制剂,用于三阴性乳腺癌(TNBC)中针对半乳糖凝集素-3(Gal-3)的俄歇化疗。该制剂利用柑橘果胶二醛(CPDA)制备能够在肿瘤中响应性释放化疗药物阿霉素(Dox)的纳米颗粒,并掺入放射性核素碘-125用于俄歇治疗。基于CPDA的核壳纳米颗粒(CPDANP)通过CPDANP聚合物链之间的硼酸酯键和用于将Dox与CPDANP偶联的亚胺键(CPDANP-Dox),设计用于在肿瘤微环境中释放药物Dox。通过动态光散射(DLS)和透射电子显微镜(TEM)对纳米颗粒的大小、有效电荷和核壳样结构进行表征,并用碘进行放射性标记。通过荧光显微镜和估计细胞分离核中的放射性,证实了CPDANP-Dox和碘对肿瘤细胞核的Gal-3特异性靶向。体外和体内研究表明,[I]I-CPDANP-Dox联合治疗在TNBC细胞中表现出增强的细胞毒性。单光子发射计算机断层扫描(SPECT)成像和生物分布研究表明制剂从血液中快速清除,4T1荷瘤小鼠的肿瘤消退研究证实联合治疗相对于单一疗法具有治疗优势。本研究突出了CPDANP作为双靶向平台在TNBC治疗中进行高效俄歇化疗的潜力。