Tumor-targeting and imaging micelles for pH-triggered anticancer drug release and combined photodynamic therapy

Abstract

Herein, we construct a charge - switchable polymer nano micelles poly (2-(hexamethyl eneimino) ethyl methacrylate) - b - poly (ethylene glycol) monomethyl ether methacrylate) - b - poly (diethyl enetriaminepentaacetic acid methacrylate) - b - poly (1-vinyl imidazole) - b - poly (4-vinyl phenylboronic acid) (PC7A-PEG-DTPA-VI-PBA) in different pH solutions. DOX released faster from micelles in a weakly acidic environment (pH 5.0) than at pH 7.4. In order to enhance the anti-tumor effect, the imidazole functional groups in the polymer were used to coordinate CdSeTe quantum dots (QDs) for photodynamic treatment (PDT). In addition, the surfaces of the micelles were further decorated with phenylboronic acidas a targeting group, using DTPA chelating 99mTc for SPECT imaging.It has been successfully demonstrated that the nanoparticles have a good cumulative effect on the tumor site.The structure of the polymer was characterized by 1HNMR. The morphology and particle size of the micelles were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The drug loading capacity (DLC) and drug loading efficiency (DLE) of the micelles were analyzed by ultraviolet visible spectroscopy. And the pH-sensitive drug release and cytotoxicity of the micelles were verified in vitro. In vitro experiments showed that the nano micelles were noncytotoxic to different cell lines, while DOX@CdSeTe@PC7A-PEG-DTPA-VI-PBA inhibited the proliferation and promoted the apoptosis of B16F10 cells. An in vivo study with C57BL tumor-bearing mice indicated that DOX@CdSeTe@PC7A-PEG-DTPA-VI-PBA nano micelles efficiently inhibited tumor growth. Results showed that the nano micelles had good pH responsibility and biocompatibility, and the loaded DOX could be released in the weak acidic environment of tumor cells, and it was expected to be a good drug delivery system.