Improving lung cancer treatment: Hyaluronic acid-modified and glutathione-responsive amphiphilic TPGS-doxorubicin prodrug-entrapped nanoparticles

Lung cancer nanotherapeutics aim to overcome the limitations of conventional therapeutic methods. In the present study, a self-assembled amphiphilic prodrug-based nanocarrier delivery system was developed that exhibited high therapeutic efficiency. D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) conjugated to doxorubicin (DOX) through disulfide (S-S) bonds to constitute TPGS-S-S-DOX was synthesized; furthermore, hyaluronic acid (HA) was conjugated to TPGS to obtain HA-TPGS. TPGS-S-S-DOX prodrug-based and HA-TPGS ligand-modified nanoparticles (HA-TPGS DOX-NPs) were prepared for the treatment of lung cancer. In vitro and in vivo evaluation of the system was performed on lung cancer cell lines and lung tumor-bearing mice. HA-TPGS DOX-NPs had a uniformly spherical shape with a white core and grey shell, with a size of 172.3 nm and a polydispersity index of 0.16. All of the NPs exhibited a drug encapsulation efficiency of >90%. The blank NPs exhibited low toxicity to all the tested cell lines, resulting in viabilities of >85%. HA-TPGS DOX-NPs had a more prominent in vitro antitumor effect than the other NPs tested, with cell viabilities of 80.2, 73.4, 57.8, 39.1, 28.3 and 10.9% observed after 72 h of incubation with 0.01, 0.05, 0.1, 0.5, 1 and 5 mu M, respectively. The in vivo results demonstrated that HA-TPGS DOX-NPs had the highest antitumor efficacy, with 10.5% tumor inhibition efficiency after 28 days of injection. Overall, HA-TPGS DOX-NPs had significant antitumor effects and minimal systemic toxicity, and their application may be a promising strategy for the treatment of lung cancer.