A single-beam of light priming the immune responses and boosting cancer photoimmunotherapy.

Mirroring the rapid clinical performance, immune checkpoint blockade (ICB) leads a remarkable clinical advance in combating cancer, but suffers poor response in most cancers. The low presence of tumor-infiltration lymphocytes and the poor immunogenicity in tumor microenvironment (TME) are the main factors hindering the effectiveness of ICB in the treatment of immunological "cold" tumors. Aiming at boosting immune response via TME modulation, we report a near-infrared laser-guided photoimmuno-strategy in which synergistic phototherapy, immune adjuvant, and ICB are integrated into one versatile nanoporphyrin platform. The prepared nanoporphyrins are self-assembled from purpurin18-lipids and have photodynamic/photothermal and immunomodulatory effects that can be tuned under a single laser irradiation, concomitant with fluorescence or MSOT imaging. In this work, the contributions of each component in the nanoporphyrin platform were specified. In particular, phototherapy-driven in situ tumor cell death provided abundant tumor-associated antigens to initiate immune responses. With the assist of spatiotemporally delivered immune adjuvant, phototherapy potentiated tumor immunogenicity, reprogrammed "cold" tumors into "hot" ones, and sensitized tumors to ICB therapy. Further combined with PD-L1 blockade, the photoimmune-strategy substantially stimulated tumor-specific immune-responses and long-term immunological memory against primary tumor, abscopal tumor as well as metastatic foci. Such single light-primed photoimmunotherapy offers a promising solution to overcome common hurdles in ICB treatment and can potentially be integrated into existing clinical practice.

Correction to "Highly Efficient Water-Soluble Photosensitizer Based on Chlorin: Synthesis, Characterization, and Evaluation for Photodynamic Therapy".

[This corrects the article DOI: 10.1021/acsptsci.1c00004.].

Highly Efficient Water-Soluble Photosensitizer Based on Chlorin: Synthesis, Characterization, and Evaluation for Photodynamic Therapy.

The clinical applications of many photosensitizers (PSs) are limited because of their poor water solubility, weak tissue penetration, low chemical purity, and severe toxicity in the absence of light. We designed a novel chlorin-based PS (designated as HPS) to achieve fluorescence image-guided photodynamic therapy (PDT) with efficient ROS generation. In addition to its simple fabrication process, HPS has other advantages such as excellent water solubility, strong NIR absorption, and high biocompatibility upon chemical functionalization for enhanced phototherapy. HPS exhibited high photodynamic performance against lung cancer and breast cancer cells by generating a large amount of singlet oxygen (1O2) under 654 nm laser irradiation. HPS accumulated into multiple organelles such as mitochondria and the endoplasmic reticulum and triggered cell apoptosis by laser exposure. In the tumor-bearing mice, in vivo, HPS showed an optimal half-life in circulation and achieved fluorescence-image-guided PDT within the irradiation window, resulting in effective tumor growth inhibition and the prolonged survival of animals. Moreover, the antitumor PDT effect of HPS was close to the clinical trial phase II stage of HPPH even at the low dosage of 0.32 mg/kg (under 75 J/cm2 laser), while the systemic safety of HPS was much higher. In conclusion, HPS is a novel water-soluble chlorin derivative with excellent PDT potential for clinical transformation.