Enhanced Upconversion Luminescence-Guided Synergistic Antitumor Therapy Based on Photodynamic Therapy and Immune Checkpoint Blockade
Bi Lin, Jun Liu, Yanxing Wang, Fan Yang, Liyu Huang, Ruichan Lv
Abstract
In this research, a new type of mitochondrial-imaging probe using spindle nanocomposite with adjustable aspect ratios and enhanced upconversion luminescent (UCL) property was designed for synergistic immune–photodynamic anticancer theranostics. Gold nanoparticles are coated on the surface of a spindle-like probe layer-by-layer (LBL), which makes the probe have better red UCL enhancement under the NIR excitation, and the surface plasmon resonance (SPR) peak can be exactly predicted by discrete dipole scattering calculation. The mitochondrial imaging experiments show that the probe modified with ethylenebis(nitrilodimethylene)tetraphosphonic acid (EDTMP) has better biocompatibility and can achieve real-time dynamic imaging of mitochondria, revealing its potential preclinical bioimaging use. In addition, a monoclonal antibody of anti-CTLA-4 was used as an immune checkpoint blockade to promote the activation of immune response and enhance the photodynamic therapy (PDT) to kill cancer cells. The in vivo compatibility, blood routine, bioimaging, and anticancer results reveal that the combination of SPS@Au and ZnPc (SPSZ) was a potential synergistic immune–photodynamic therapy (PDT) candidate with enhanced UCL and good biocompatibility.