Functional evaluation of doxorubicin decorated polymeric liposomal curcumin: a surface tailored therapeutic platform for combination chemotherapy

Abstract

Recent advances in nanotechnology have revolutionized nanomedicine to concurrently deliver multiple drugs for combination chemotherapy. Despite some improvements in drug delivery systems, the accommodation of combination chemotherapeutics in hybrid nanostructures with tunable chemistry remains a challenge. Here, we have made a hypothesis and designed a new platform for the accommodation of curcumin and doxorubicin in surface engineered liposomes. The liposome surface is engineered by one-step polyelectrolyte (poly(sodium 4-styrene sulfonate) (PSS)) coating to accommodate curcumin (CUR) in the phospholipid bilayer and doxorubicin (DOX) on the polymeric liposomal surface (DOX-PSS@lipo-cur). Infusion of CUR drug molecules between the phospholipid bilayers is visualized by confocal laser scanning microscopy images. The conjugation strategy of DOX with and without the polymeric platform can be distinguished from fluorescence measurements. The quenching mechanism of PSS@lipo-cur with DOX is intricately studied and the nature of the quenching process evaluated from fluorescence lifetime measurements which show the effective binding based on static quenching rather than dynamic. The stability of the nanoformulation and engineered liposomal surface is validated through the zeta potential and TEM micrographs. The hemolysis assay revealed that the nanoformulation ameliorates the toxicity of DOX which paves the way for in vivo applications. Further, in vitro studies reveal the effective inhibition of cellular proliferation, cellular internalization and apoptosis which evidences high therapeutic efficacy in MCF-7 breast cancer cells. The decoration of DOX on PSS@lipo-cur has empowered a new strategy to improve the therapeutic efficacy. The present findings provide an insight into the design of various conjugation strategies on a liposomal surface for combination chemotherapy.