Photochemical internalization (PCI) is a further development of
photodynamic therapy (
PDT). In this report, we describe PCI as a potential tool for cellular internalization of chemotherapeutic agents or
antigens and systematically review the ongoing research. Eighteen published papers described the pre-clinical and clinical developments of PCI-mediated delivery of chemotherapeutic agents or
antigens. The studies were screened against pre-defined eligibility criteria. Pre-clinical studies suggest that PCI can be effectively used to deliver chemotherapeutic agents to the cytosol of
tumor cells and, thereby, improve treatment efficacy. One Phase-I clinical trial has been conducted, and it demonstrated that PCI-mediated
bleomycin treatment was safe and identified tolerable doses of the
photosensitizer disulfonated tetraphenyl
chlorin (TPCS2a). Likewise, PCI was pre-clinically shown to mediate major histocompatibility complex (MHC)
class I antigen presentation and generation of
tumor-specific cytotoxic CD8+ T-lymphocytes (CTL) and
cancer remission. A first clinical Phase I trial with the
photosensitizer TPCS2a combined with human papilloma virus
antigen (HPV) was recently completed and results are expected in 2020. Hence,
photosensitizers and light can be used to mediate cytosolic delivery of endocytosed chemotherapeutics or
antigens. While the therapeutic potential in
cancer has been clearly demonstrated pre-clinically, further clinical trials are needed to reveal the true translational potential of PCI in humans.