Nanoparticles from supramolecular polylactides overcome drug resistance of cancer cells

Abstract

A major drawback of chemotherapy is that cancer cells can develop multi-drug resistance, leading to failure of anticancer treatments. To overcome this limitation, we report the preparation of environment-sensitive polylactide (PLA)-based nanoparticles, assembled by multiple hydrogen bonds. These nanoparticles showed sizes in the 100–150 nm range, a spherical morphology, and low toxicity in cell culture. In addition, their 3D supramolecular polymer network was sensitive to both pH and temperature and yielded dynamically reversible networks that could recognize the intrinsic differences between cancer and normal tissues. Release studies of the encapsulated anticancer drug doxorubicin (DOX) demonstrated that the nanoparticles exhibited high stability at physiological conditions. However, when the pH was reduced from 7.4 to 5, an accelerated release was observed. Most importantly, by applying this supramolecular linked nanocarrier for the delivery of DOX, the drug-resistance of KB-V1 cells could be overcome. All these features demonstrate the versatility of the proposed modular approach and their great potential for anticancer therapy.