Tumor growth inhibition and adverse effect reduction together with
metastasis alleviation are still the challenges that need to be overcome in
cancer chemotherapy. Combinational
therapy provides an alternative
solution for these challenges. Nanoparticles are the ideal carriers for combinational
therapy due to their versatile
drug loading capacities and versatile
tumor-targeting strategies. In this study, a cRGDfk modified
nanogel system has been utilized to coload
lidocaine, a voltage-gated Na+ channels inhibitor, and
cisplatin, a common anticancer
drug to obtain a
tumor-targeted dual drugs-loaded
nanogel system. The introduction of
lidocaine not only promotes the
cisplatin-induced apoptosis in vitro and in vivo but also alleviates the
metastasis of MDA-MB-231
breast cancer cells in the mouse model. Besides, the
body weight loss caused by
cisplatin has also been relieved, and higher dose with less
body weight loss can be achieved, which indicated the adverse effect caused by
cisplatin-mediated
chemotherapy has been alleviated. Furthermore, the introduction of
peptide segment-cRGDfk, which presents high affinity to αvβ3
integrin, further increases the enrichment of
drug-loaded
nanogel in the
tumor site. It favors the primary
tumor growth inhibition. The results demonstrate the coloading of
lidocaine and
cisplatin by
ligand-modified
nanogels is a promising strategy for αvβ3
integrin-overexpressing
breast cancer combinational
therapy.