3-Carboxyphenylboronic acid-modified carboxymethyl chitosan nanoparticles for improved tumor targeting and inhibitory

Carboxymethyl chitosan-based nanoparticles (CM NPs) were prepared, and were further modified with a tumor-homing ligand (3-carboxyphenylboronic acid, 3-CPBA) to give tumor-targeting nanoparticles (CB NPs). Particle sizes were measured by dynamic light scattering, while the morphology was observed via transmission electron microscopy and scanning electronic microscope. The results show that CM and CB NPs are spherical-like, and kinetically stable in various conditions. Doxorubicin (DOX) as a model drug was successfully encapsulated to give CM-DOX and CB-DOX NPs. The biological effect of these DOX-loaded NPs was then investigated by monolayer cell model and three-dimensional multicellular spheroids (MCS). The results demonstrate that 3-CPBA modification can improve NPs' accumulation and penetration ability. In vivo antitumor effect was evaluated by H22 lung metastasis tumor-bearing mice. CB-DOX NPs can deliver more drug than CM-DOX NPs, and retain for a long time in lung tissue, thus remarkably reducing the size of tumor mass of H22 metastasis lung tumor. All results demonstrate that the obtained NPs would be potentially useful as nano-scaled drug carriers in chemotherapy.