pH-tunable nanoparticles composed of copolymers of lactide and allyl-glycidyl ether with various functionalities for the efficient delivery of anti-cancer drugs.

The designing of biocompatible nanocarriers for the efficient delivery of their cargos to the desired targets remains a challenge. In this regard, the most promising strategy relies on the construction of pH- or thermo-responsive nanoparticles (NPs). However, it is also important to preserve the balance between the responsiveness of the carrier and their stability in physiological conditions. Therefore, we described a new family of copolymers of lactide and allyl-glycidyl ether which were subsequently modified by thiol-ene reaction to functionalize the resulting copolymer with acetylcysteine (ACC) or thioglycolic acid (tGA) moieties. Subsequently, these copolymers were used to obtain blank and doxorubicin (DOX) loaded NPs with an average diameter of about 50-100 nm. Interestingly, the NPs were stable in different pH conditions, however, the presence of ACC or tGA units in the polymeric chain allows for the reduction of the undesired burst release due to the supramolecular interactions between polymeric pedant groups and DOX. The release tests of DOX from NPs showed that DOX release rate decrease depending on the pH values and the copolymer functionalization in order of non-modified NPs > ACC-modified NPs > tGA functionalized NPs. Most importantly, the MTT assay showed that all blank NPs are non-toxic against the normal L929 cell line. Subsequently, the antitumor efficiency of the obtained NPs was tested towards L929 (murine fibroblast cell line), HeLa (cervical cancer), and AGS (human gastric adenocarcinoma cancer) cells. The results demonstrated that DOX-loaded NPs efficiently induce the reduction in the viability of the HeLa and AGS cell, and this reduction in the viability was even below 20 % for the AGS cells. Together with their biocompatibility, the obtained NPs offer a novel route for the preparation of nanocarriers for the controlled and efficient delivery of anticancer drugs.