Could Photodynamic Therapy Be a Promising Therapeutic Modality in Hepatocellular Carcinoma Patients? A Critical Review of Experimental and Clinical Studies

Abstract

Photodynamic Therapy (PDT) relies on local or systemic administration of a light-sensitive dye, called photosensitizer, to accumulate into the target site followed by excitation with light of appropriate wavelength and fluence. This photo-activated molecule reacts with the intracellular oxygen to induce selective cytotoxicity of targeted cells by the generation of reactive oxygen species. Hepatocellular carcinoma (HCC), one of the leading causes of cancer-associated mortality worldwide, has insufficient treatment options available. In this review, we discuss the mechanism and merits of PDT along with its recent developments as an anti-cancerous therapy. We also highlight the application of this novel therapy for diagnosis, visualization, and treatment of HCC. We examine the underlying challenges, some pre-clinical and clinical studies, and possibilities of future studies associated with PDT. Finally, we discuss the mechanism of an active immune response by PDT and thereafter explored the role of PDT in the generation of anti-tumor immune response in the context of HCC, with an emphasis on checkpoint inhibitor-based immunotherapy. The objective of this review is to propose PDT as a plausible adjuvant to existing therapies for HCC, highlighting a feasible combinatorial approach for HCC treatment.

Multiple Light-Activated Photodynamic Therapy of Tetraphenylethylene Derivative with AIE Characteristics for Hepatocellular Carcinoma via Dual-Organelles Targeting

“…Multiple treatment sessions and repetitive puncture operation may be required due to difficult tumor conditions and limitation of imaging technology, which may cause additional suffering of patients [4]. Alternatively, photodynamic therapy (PDT) is a potential tumor-ablative locoregional therapy [5][6][7]. Fluorescent molecules with photodynamic effect can provide precise and safe ablation of tumor at the cellular level while enabling dynamic monitoring of tumor lesion, which has great promise in building cancer-targeted theragnostic platforms [8,9].…”

“…Additionally, intraoperative fluorescence image-guided surgery combined with PDT can eliminate residual tumors and reduce the recurrence of cancer [12][13][14][15]. The use of PDT has gained much attention in the treatment of HCC, and has been approved as a feasible approach for HCC treatment in preclinical studies [6,16].…”

Progress in Nanocarriers Codelivery System to Enhance the Anticancer Effect of Photodynamic Therapy

“…There are many factors that contribute to decline in photodynamic therapy, including the metastatic tumor at unknown sites, inadequate light delivery, lack of sufficient oxygen and induction of an anti-PDT effect [1]. To overcome these limitations and to improve efficiency, the researchers have combined PDT with other treatments.…”

“…Photodynamic therapy (PDT) is a modern noninvasive antitumor technique that has great clinical application potential due to its advantages of simple operation and low systemic toxicity. PDT has been clinically approved for the treatment of some tumors, such as advanced esophageal cancer and advanced lung cancer [1]. Local or systemic photosensitizers (PSs) can be activated to produce cytotoxic reactive oxygen species (ROS) after absorbing light from an appropriate wavelength laser, which can induce tumor cell necrosis and apoptosis or cause angiotoxicity to block tumor cell nutrient supply.…”

Photodynamic and Photothermal Therapy of Hepatocellular Carcinoma

“…PDT takes advantage of the active metabolism of tumor tissue; whereby non-toxic photosensitizers accumulate in tumor tissue after injection. When the tumor tissue is irradiated with harmless visible light, the activated photosensitizer transfers its energy to surrounding intracellular oxygen that forms reactive oxygen species (ROS), which specifically destroy the tumor cells and neovascularization ( 14 – 17 ) ( Figure 1 ).…”