Reversing microtubule-directed chemotherapeutic drug resistance by co-delivering α2β1 inhibitor and paclitaxel with nanoparticles in ovarian cancer

Previous reports indicated that integrins associated signals are tightly related to tumor progression. Here, we observed elevated expression of Integrin α2β1 in tumor tissues from microtubule-directed chemotherapeutic drugs (MDCDs) resistant patients compared with the samples from chemosensitive patients. More importantly, we sorted the Integrin α2β1⁺ tumor cells and found those cells revealed high MDCDs resistance, whereas MDCDs shows effective cytotoxicity to those Integrin α2β1^- tumor cells in vitro and in vivo. Mechanistically, we demonstrated that Integrin α2β1 could induce MDCDs resistance through the activation of the PI3K/Akt pathway. Applying MPEG-PLA to co-encapsulate the integrin α2β1 Inhibitor E7820 and MDCDs could effectively reverse MDCDs resistance, resulting in enhanced Anticancer effects while avoiding potential systemic toxicity in vitro and in vivo. In conclusion, the expression of Integrin α2β1 contributes to MDCDs resistance, while applying E7820 combination treatment by MPEG-PLA nanoparticles could reverse the resistance.