Near-infrared and pH responsive molecular machine for controlled encapsulation and release of drugs

It is difficult to form nanoparticles by traditional polymerization methods, using the azobenzene monomer with large hindrance. In this work, distillation precipitation polymerization (DPP) with lowering the monomer content at the beginning and distilling the solvent at a constant speed. Monofunctional 6-(4-methoxy-4′-oxygen-azobenzene) hexyl methacrylate (Azo) as a photo-responsive monomer and methacrylic acid (MAA) as a pH responsive monomer, were used to synthesize UCNPs@SiO2@PAzo/MAA nanoparticles. After the SiO2 was etched, UCNPs@PAzo/MAA nanocapsules (NCs) were formed. The trans isomer in the PAzo shell is converted into cis under 980 nm near-infrared (NIR) irradiation, leading to a variation of size and hydrophilicity of the nanocapsules. Controlled drug loading (∼17.5%) could be performed using UV irradiation, in which the pendant Azo groups have an cis “open” state and larger hydrophilicity. Under weak acid and NIR irradiation, the pendant Azo group with constant isomerization is like a “molecular impeller” agitator and the cumulative release rate of the doxorubicin (DOX) reaches 67.88%. Furthermore, UCNPs@PAzo/MAA nanocapsules were applied to the intracellular environment, and the cytotoxicity was studied. The cell images and cytotoxicity studies showed that the drug could be efficiently delivered to the nucleus by the UCNPs@PAzo/MAA nanocapsules in a controlled manner.