Reconstructing the Intracellular pH Microenvironment for Enhancing Photodynamic Therapy
Tumor acidic microenvironment, characterized with weak acid outside cell (pH~6.5-7.0), has been revealed as a potential therapeutic target with the specific acid-responsible materials. However, the intracellular pH of tumor cells is still slightly alkaline (pH~7.2-7.4), which is not conducive for nanomaterials that respond to acid but should destroy intracellular substances. Here, we proposed a new strategy for reconstructing the intracellular pH microenvironment to enhance photodynamic therapy. The nanomaterials (UCNP@ZIF+TPP+PA) were designed with NaYF4:Yb:Tm (UCNP) inner core coated by the porous zeolitic imidazolate framework (ZIF-8) outside for photoacid (PA) and acid-responsive porphyrin (TPP) co-loading. Upon 980 nm laser irradiation, the emission light of UCNP activates PA for H+ release, which achieves reconstructing the intracellular pH environment. At this new acid condition, TPP becomes protonated (TPP-H+), which reduces its aggregation by enhancing its water solubility, and in turn increases singlet oxygen (1O2) production for enhanced tumor killing. Both in vitro and in vivo experiments have proved that UCNP@ZIF+TPP+PA could reconstruct the intracellular pH environment and enhance therapeutic effect of photodynamic therapy (PDT). Reconstructing the intracellular pH by light is of great significance for acid-responsive nanosystem to destroy the intracellular substances and treat tumors. The results also signify the use of such acid-responsive materials for several other disease therapies.