Oleanolic acid-conjugated human serum albumin nanoparticles encapsulating doxorubicin as synergistic combination chemotherapy in oropharyngeal carcinoma and melanoma

Combination chemotherapy produces a superior therapeutic response than monotherapy in cancer. Human serum albumin and a naturally occurring cancer prophylactic/anticancer triterpenoid, oleanolic acid, were conjugated to form self-assembled nanoparticles that entrapped doxorubicin. Dox@HSA-OA NPs were physicochemically characterized for particle size, zeta potential, drug loading, entrapment efficiency, stability, release, and hemocompatibility. The Dox@HSA-OA NPs (particle size. ~ 140 nm) showed commendable loading (14.6 %), entrapment (59.01%) of Dox. The in vitro cell uptake study using human oral squamous carcinoma (FaDuHTB-43) and murine melanoma (B16F10) cells indicated a higher cellular association of Dox@HSA-OA NPs than free Dox. The lowest IC50 of Dox@HSA-OA NPs than Dox against both the cell lines at various time points proved the Dox/HSA-OA-mediated combination chemotherapeutic effect. Dox@HSA-OA NPs demonstrated higher apoptosis and cell cycle arrest (G2/M phase). The Dox@HSA-OA NPs-mediated Dox penetration, cell death/shrinkage were significant in FaDu-HTB-43 spheroids. Dox@HSA-OA NPs showed a better pharmacokinetic profile with increased t(1/2) and Cmax than Dox. The in vivo experiment using B16F10 tumor-bearing mice showed tumor regression, DNA damage, oxidative stress, and apoptosis-induction via the intrinsic pathway to a greater extent following Dox@HSA-OA NPs treatment than Dox. Therefore, the Dox@HSA-OA NPs-mediated combination therapy could be a powerful treatment strategy for solid tumors.

Automated summary

Combination chemotherapy with self-assembled nanoparticles of human serum albumin and oleanolic acid, entrapping doxorubicin, demonstrated superior therapeutic effects in vitro and in vivo, with increased cellular uptake, apoptosis induction, and tumor regression. It could be a powerful treatment strategy for solid tumors.