In this study, we developed a novel hybrid collagen-binding nanocarrier for potential intraductal administration and local breast cancer treatment. The particles were formed by the encapsulation of nanostructured lipid carriers (NLCs) containing the cytotoxic drug paclitaxel within a shell of poly(N-isopropylacrylamide) (pNIPAM), and were functionalized with SILY, a peptide that binds to collagen type I (which is overexpressed in the mammary tumor microenvironment) to improve local retention and selectivity. The encapsulation of the NLCs in the pNIPAM shell increased nanoparticle size by approximately 140 nm, and after purification, a homogeneous system of hybrid nanoparticles (∼96%) was obtained. The nanoparticles exhibited high loading efficiency (<76%) and were capable of prolonging paclitaxel release for up to 120 h. SILY-modified nanoparticles showed the ability to bind to collagen-coated surfaces and naturally elaborated collagen. Hybrid nanoparticles presented cytotoxicity up to 3.7-fold higher than pNIPAM-only nanoparticles on mammary tumor cells cultured in monolayers. In spheroids, the increase in cytotoxicity was up to 1.8-fold. Compared to lipid nanoparticles, the hybrid nanoparticle modified with SILY increased the viability of nontumor breast cells by up to 1.59-fold in a coculture model, suggesting the effectiveness and safety of the system.
Keywords: breast cancer; collagen binding peptide; lipid-polymeric nanoparticles; paclitaxel; poly(N-isopropylacrylamide) (pNIPAM).