A Sequential Stimulus-Responsive Nanoparticle Platform for Enhanced Tumor Growth Inhibition and Efficient Drug Delivery

Purpose In this study, we fabricated a nanoplatform to target tumor sites via active and passive targeting effects, thus avoiding the toxic side effects of nanocarriers and improving the efficacy of chemotherapeutic drug delivery. Methods A sequential stimulus-responsive nanoparticle that targeted the tumor microenvironment and exhibited dual sensitivity to the reduction condition and matrix metalloproteinase-9 (MMP-9) enzyme was fabricated based on a self-assembled polypeptide-paclitaxel conjugate. Results The nanoparticles (48.9 ± 2.1 nm) transformed into rod-like nanostructures (297.1 ± 3.2 nm) in the presence of MMP-9. The rod-like nanostructures were taken up by tumor cells and then sensitive bonds were broken in response to highly expressed GSH in tumor cells to release drugs. This platform showed a tumor inhibition rate of 71.8% in S180-bearing mice and a more effective tumor inhibition rate than Taxol in 4T1-bearing mice. Conclusion This platform facilitates the design of enhanced safe and efficient chemotherapy drug delivery.