Collagen-Binding Nanoparticles for Paclitaxel Encapsulation and Breast Cancer Treatment

Abstract

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.

Thermosensitive Polymeric Nanoparticles for Drug Co-Encapsulation and Breast Cancer Treatment

“…Given that collagen is a predominant component of the tumor microenvironment, and its content and structure are substantially altered by mutations in tumor suppressor genes in cancer cells, collagen affinity provides a strategic avenue for targeted therapy [ 10 ]. Consistent with earlier studies [ 43 , 76 ], we observed that nanoparticles modified with SILY successfully adhered to a collagenous matrix, a property not observed in nonmodified nanoparticles. In line with this finding, the nanoparticles provided longer retention in vivo in the mammary tissue compared to a simple solution.…”

“…The IC 50 values obtained in the spheroids were higher than those obtained in monoculture, which was previously related to the limitation of drug penetration into the spheroid core [ 76 ]. Consistent with the findings observed in monolayer cultures, nanoencapsulation markedly reduced the piplartine IC 50 across both examined cell line spheroids.…”

“…Additionally, the size reduction of pNIPAM nanoparticles at body temperature might make them more suitable for endocytosis, the primary mechanism for cellular internalization of nanoparticles. While Figure 6 does not directly show particle uptake, in a recent work by our group, it was observed that SILY-modified PNIPAM nanoparticles undergo clathrin-mediated endocytosis by breast cancer cells; lipid nanoparticles coated with SILY underwent endocytosis mediated by both clathrin and caveolin, suggesting a greater influence of the composition of the nanoparticle itself than that of the SILY coating [ 76 ]. Nevertheless, SILY molecules, when attached to the surface of nanoparticles, can specifically bind to collagen, which is abundant in the extracellular matrix of tissues and facilitates the localization of the nanoparticles near the target cells, potentially increasing the likelihood of cellular uptake.…”