Cholesterol-paclitaxel conjugate nanoparticles for in vivo hitchhiking of serum albumin to enhance antitumor efficacy

Self-delivery systems are considered to be a promising strategy to optimize drug formulation and improve treatment outcomes. Herein a paclitaxel (PTX) prodrug was designed by modifying PTX with cholesterol molecule with the disulfide bond as the bridging group. The self-delivery PSSch NPs with high content of PTX up to 61.6 ​wt% were obtained by the self-assembly of as-synthesized PTX prodrug in the absence of any adjuvants. PSSch NPs had good colloidal stability and strong interaction with serum albumin. The non-covalent binding to albumin not only accelerated drug release in a reductive environment, but also enhanced cellular endocytosis by tumor cells. After intravenous injection, PSSch NPs exhibited preferential tumor accumulation and superior tumor inhibition effects with the help of serum albumin. This study provides a vital guide for the construction of self-delivery nanoformulations for potentiated chemotherapy. • Modification with cholesterol endows the paclitaxel prodrug with good self-assembly ability. • Binding of PSSch NPs to albumin promoted reductive-responsive drug release. • PSSch NPs had enhanced cellular internalization after interaction with HSA.