Abstract
Background: Targeting cancer tumors using PLGA (Poly(D, L-lactide-co-glycolide)) nanoparticles (NPs) requires clathrin-mediated endocytosis (CME) and lysosomal degradation to provide release within cancer cells. However, Caveolae-mediated endocytosis (CavME) provides lysosomal escape, which is favorable in oral applications. Macropinocytosis (MPC) is a non-targeted way of endocytosis, used by immune cells. Methods: In this proof-of-concept study, we investigated how polysaccharide surface coatings modulate the endocytic uptake of FITC-labeled PLGA nanomicelles (FPM) in MCF-7 breast cancer cells using spectrophotometry. This research involved the surface modification of FPM using polysaccharides: cellulose (FPCM) as a polyglucan and Halomonas Levan (FPLM) as a polyfructan, to modify the NP and cell-surface association. Results: MPC was found to be the major internalization pathway for the nanomicelles ~200 nm. However, after surface modification, FPCM and FPM remained highly MPC-dependent with additional CavME/CME involvement, whereas FPLM showed relatively reduced MPC dependence and a higher CME contribution. Conclusion: Overall, the results indicate that simple polysaccharide coatings can bias the relative use of MPC, CME, and CavME for PLGA nanomicelles in MCF-7 cells, providing a basis for pathway-oriented nanocarrier design. Validation by flow cytometry, studies in additional breast cancer cell lines, and transporter-level investigations will be needed to generalize and refine these findings.