Published online Nov 24, 2022. doi: 10.5306/wjco.v13.i11.880
Peer-review started: August 3, 2022
First decision: August 29, 2022
Revised: September 12, 2022
Accepted: October 18, 2022
Article in press: October 18, 2022
Published online: November 24, 2022
Photodynamic therapy (PDT) is one of the emerging options to combat cancer and it requires pho
We previously developed a folate-linked, near-infrared (NIR)-sensitive probe folate-Si-rhodamine-1 (FolateSiR-1). The feasibility of NIR-PDT using FolateSiR-1 and appropriate light irradiation had not been determined and reqired elucidation.
The aim of this study was to evaluate the photodynamic therapeutic efficacy of FolateSiR-1 in a preclinical cancer model and determine the cell death mode induced by FolateSiR-1-based PDT.
FolateSiR-1 was synthesized by conjugating a folate moiety to the Si-rhodamine derivative through a negatively charged tripeptide linker. Utilizing FR-overexpressing cell line KB and low FR-expressing cell lines OVCAR-3 and A4, selective binding of FolateSiR-1 to FR was evaluated by fluorescence microscopy. Cell viability imaging assays was exploited to assess the phototoxic effect of FolateSiR-1. In vivo longitudinal fluorescence imaging was conducted to examine the time-dependent biodistribution of FolateSiR-1 and its specific accumulation in KB tumors. To evaluate PDT efficacy of FolateSiR-1, KB tumor-bearing mice were divided into four groups: (1) FolateSiR-1 alone; (2) FolateSiR-1 followed by NIR irradiation; (3) NIR irradiation alone; and (4) no treatment. Tumor volume measurement, as well as immunohistochemical (IHC) and histological examinations of tumors were performed to determine the effect of PDT.
FR-specific binding of FolateSiR-1 was observed by fluorescence microscopy and in vivo fluorescence imaging. Cell viability imaging assays indicated that NIR-PDT induced cell death. In vivo longitudinal fluorescence imaging showed rapid peak accumulation of FolateSiR-1 in KB tumors 2 h after injection. The tumor volumes in the PDT group were significantly reduced compared to the other groups (P < 0.05). IHC analysis revealed reduced numbers of proliferation marker Ki-67-positive cells in PDT treated tumors, and hematoxylin-eosin staining revealed features of necrotic- and apoptotic cell death.
FolateSiR-1 may be effectively utilized in PDT with low side effects, and the FR-targeted NIR-PDT can potentially reveal new strategies for the treatment of FR-overexpressing tumors.
The fascinating features of FolateSiR-1, including specificity to FR, cytotoxicity in combination with NIR irradiation and relatively fast clearance implying low toxicity, prompted the development of an alternative PS for NIR-PDT. The therapeutic effect was significant after a single dose of irradiation and may be optimized to achieve patient-specific clinical effects. Moreover, fluorescence emission from FolateSiR-1 may be used for real time cancer detection and patient screening for treatment selection. Further research may elucidate these additional details of these processes.