Targeted Delivery of Doxorubicin by PLGA Nanoparticles Increases Drug Uptake in Cancer Cell Lines

Abstract

Doxorubicin (DOX) is an anthracycline drug widely used in the treatment of a large spectrum of solid tumors. Its application is limited by its efflux through the multidrug resistance (MDR) protein. In this study, we explored the potential of DOX - PLGA nanoparticles (DNPs) and antibody decorated nanoparticles (ADNPs) to overcome MDR in cancer cells. DNPs were prepared by the O/W emulsion solvent evaporation method. The surface decoration of nanoparticles with antibody was performed via carbodiimide reaction. The particles were characterized for their size and zeta potential, and their in vitro uptake was compared with their unconjugated counterparts. Entrapment efficiency of DNPs and ADNPs was measured by fluorescence using the DMSO burst release procedure. Cytotoxicity was measured using the SRB assay. The DNP and ADNP nanoparticles had average diameter of 162.6 ± 2.0 nm and 213.0 ± 3.5 nm respectively. Their corresponding surface charges were -13.2 ± 2.3 mV and -1.3 ± 3.8 mV respectively. Our results showed that cellular uptake of DOX from DNPs in DOX-resistant MES-SA/Dx5 cancer cell was higher compared to free DOX. However, the uptake of DOX from DNPs in MES-SA and SKOV-3 cancer cell lines was comparable to free DOX treatment. Next, we conjugated the DNPs with HER-2 antibody to specifically target to SKOV-3 cancer cell line and MES-SA and MES-SA/Dx5 were used as negative controls. Results showed higher uptake of DOX from ADNPs compared to free DOX and DNPs in SKOV-3. However, the cellular uptake of DOX from ADNPs was comparable to DNPs in MES-SA and MES-SA/Dx5. Cytotoxicity results were consistent with the cellular uptake data. Our study concludes that the targeted DNPs may enhance the cellular uptake and cytotoxicity in SKOV-3.