Lecithin-modified hybrid nanocarriers for enhanced locoregional therapy of melanoma: Influence of surface modification on therapeutic response.

Nanomedicine has enormous potential and can overcome the limitations of conventional methods of cancer therapy. However, a major problem is still unfavorable tumor biodistribution of nanocarriers that can lead to inefficient cancer therapy. The surface modification of nanoparticles (NPs) can increase the depth of tumor penetration and improve therapeutic outcome. This study demonstrates the enhanced therapeutic effect of lecithin-modified silica NPs (LSi NPs, < 100 nm in size, Dh ∼ 150-190 nm) loaded with anticancer drug (ATS) for locoregional therapy of melanoma. Both in vitro and in vivo investigations confirmed that the lecithin functionalization not only leads to uniform intratumoral biodistribution of NPs, but also provides a more pronounced therapeutic effect on melanoma. In particular, fluorescent imaging showed increased cellular uptake and tumor spheroid penetration (B16-F10, 4T1 and CT26 cells) in case of LSi NPs. By employing localized injection of the developed NPs, their biodistribution in the tumors was determined to be 96.35-98.84 %ID/g. The evaluation of in vivo antitumor efficiency revealed a significant reduction of the tumor growth for lecithin-modified nanocarriers (ATS@LSi NPs) compared to non-modified nanocarriers (ATS@Si NPs): ∼ 0.25 cm3versus ∼ 1.1 cm3). No unwanted side effects were observed during the therapy, as confirmed by body weight measurements and histological analysis of key organs, including the heart, lungs, liver, spleen, and kidneys. Thus, we believe this study will aid in the design of nanocarriers for cancer therapy and help to accelerate the clinical translation of nanomedicine.