Actively targeted delivery of tamoxifen through stimuli-responsive polymeric nanoparticles for cancer chemotherapy

Cancer has been one of the main healthcare problems, demanding novel therapeutic approaches to improve treatment efficiency. Chemotherapy is a primary clinical therapeutic strategy that is frequently hampered by tumor recurrence and the emergence of drug-resistant metastases. This study reported a practical method to defeat chemotherapy challenges in aggressive breast tumors with tamoxifen (Tmx)-loaded redox-sensitive nanoparticles. We studied the physicochemical and biological properties of tumor-actively targeted formulations formed by self-assembly of amphiphilic chondroitin sulfate-palmitoyl (ChS-Pal) copolymers opposing their amount of hydrophobic group. ChS-Pal exhibited more than 12% loading capacities for Tmx and desirable redoxsensitivity evaluated by in vitro release of the drug in several reducing mediums. The early apoptosis-inducing effects of Tmx-loaded nanoparticles were better than Tmx against both MCF-7 and MDA-MB-231 breast cancer cells. Moreover, fluorescence microscopy indicated that ChS-Pal nanoparticles could enter breast cancer cells. In vivo evaluation indicated that Tmx-loaded ChS-Pal nanoparticles accurately accumulated in the tumor region and prevented tumor cell proliferation more effectively than free Tmx in 4T1-bearing BALB/c mice. The resulting nanoparticles exhibited promising behavior as a chemotherapeutic drug carrier both in vitro and in vivo for efficiently combating breast cancer.

Automated summary

This study presents a practical method to overcome the challenges of chemotherapy in aggressive breast tumors using tamoxifen-loaded redox-sensitive nanoparticles. These nanoparticles exhibit enhanced apoptosis-inducing effects on breast cancer cells and can accurately accumulate in the tumor region in vivo, showing promising potential as an efficient chemotherapeutic drug carrier for combating breast cancer.