Superior antitumor effect of self-assembly supramolecular paclitaxel nanoparticles

Paclitaxel (Ptx), a microtubule depolymerization inhibitor, is one of the first-line regimens in lung cancer chemotherapy. However, the poor solubility of Ptx, as well as hypersensitivity of the solvent Cremphor EL, severely limits its clinical application. Here we developed a drug-polymer conjugate of Ptx–SA–PEG, in which amphiphilic copolymers poly(ethylene glycol) (PEG) and Ptx were conjugated by succinic acid (SA). The Ptx–SA–PEG polymers self-assemble into nanoparticles (Ptx-NPs) for efficient delivery of Ptx; cell count kit-8 assay and clonogenic assay were used to analyze the antitumor effect of Ptx-NPs. Acridine orange/ethidium bromide double staining, apoptosis analysis and western blot were measured to explore the apoptotic cell death after Ptx-NPs or free Ptx treatment. Subcutaneous xenograft models were practiced to estimate its tumor cytotoxicity and nonspecific side effects in vivo. Immunohistochemistry was used to analyze the effects of apoptosis and proliferation in tumor tissue; in vitro studies demonstrated that Ptx-NPs treatment exhibited more tumor inhibitory activity compared with free Ptx, especially at the lower doses. Moreover, Ptx-NPs activated apoptotic proteins. Animal experiments showed Ptx-NPs induced less weight loss and organ damage than free Ptx. Moreover, tumor growth was slower after Ptx-NPs treatment, indicating the superior antitumor effect and slight side effect of Ptx-NPs over free Ptx. Conjugation of Ptx–SA–PEG provides a feasible way to acquire self-assembled supramolecular Ptx-loaded nanoparticles with higher drug loading efficiency, less non-specific toxicity and more stable and durable antitumor effect of Ptx, providing a potential strategy to meliorate its clinical therapeutic efficacy.