Abstract
Photodynamic therapy (PDT) has been widely used in cancer treatment. However, hypoxia in most solid tumors seriously restricts the efficacy of PDT. To improve the hypoxic microenvironment, we designed a novel mesoporous platinum (mPt) nanoplatform to catalyze hydrogen peroxide (H(2)O(2)) within the tumor cells in situ without an extra enzyme. During the fabrication, the carboxy terminus of the photosensitizer chlorin e6 (Ce6) was connected to the amino terminus of the bifunctional mercaptoaminopolyglycol (SH-PEG-NH(2)) by a condensation reaction, and then PEG-Ce6 was modified onto the mPt moiety via the mercapto terminal of SH-PEG-NH(2). Material, cellular and animal experiments demonstrated that Pt@PEG-Ce6 catalyzed H(2)O(2) to produce oxygen (O(2)) and that Ce6 transformed O(2) to generate reactive oxygen species (ROS) upon laser irradiation. The Pt@PEG-Ce6 nanoplatform with uniform diameter presented good biocompatibility and efficient tumor accumulation. Due to the high atomic number and good near-infrared absorption for Pt, this Pt@PEG-Ce6 nanoplatform showed computed tomography (CT) and photoacoustic (PA) dual-mode imaging ability, thus providing an important tool for monitoring the tumor hypoxic microenvironment. Moreover, the Pt@PEG-Ce6 nanoplatform reduced the expression of hypoxia-inducible factor-1α (HIF-1α) and programmed death-1 (PD-1) in tumors, discussing the relationship between hypoxia, PD-1, and PDT for the first time.