Progress in Clinical Trials of Photodynamic Therapy for Solid Tumors and the Role of Nanomedicine

Abstract

Current research to find effective anticancer treatments is being performed on photodynamic therapy (PDT) with increasing attention. PDT is a very promising therapeutic way to combine a photosensitive drug with visible light to manage different intense malignancies. PDT has several benefits, including better safety and lower toxicity in the treatment of malignant tumors over traditional cancer therapy. This reasonably simple approach utilizes three integral elements: a photosensitizer (PS), a source of light, and oxygen. Upon light irradiation of a particular wavelength, the PS generates reactive oxygen species (ROS), beginning a cascade of cellular death transformations. The positive therapeutic impact of PDT may be limited because several factors of this therapy include low solubilities of PSs, restricting their effective administration, blood circulation, and poor tumor specificity. Therefore, utilizing nanocarrier systems that modulate PS pharmacokinetics (PK) and pharmacodynamics (PD) is a promising approach to bypassing these challenges. In the present paper, we review the latest clinical studies and preclinical in vivo studies on the use of PDT and progress made in the use of nanotherapeutics as delivery tools for PSs to improve their cancer cellular uptake and their toxic properties and, therefore, the therapeutic impact of PDT. We also discuss the effects that photoimmunotherapy (PIT) might have on solid tumor therapeutic strategies.

Keywords: cancer; nanotechnology; photodynamic therapy/PDT; photoimmunotherapy; photosensitizing agents; solid tumors.

Figure 1

The mechanism of photodynamic therapy (PDT) effects and a list of clinically approved Photosensitizers (PSs) with their excitation wavelengths and indications.

Figure 2

Near-infrared-Photoimmunotherapy (NIR-PIT) induce immunogenic cell death (ICD) biologically which enhances the antitumor host immunity for treating cancerous cells. Reproduced from [70].

Figure 3

NIR-PIT for treating cancer cells. This therapy can involve injecting a monoclonal antibody conjugated with a photoabsorber followed by exposure to near-infrared light at the tumor site.

Figure 4

In vivo effect of NIR-PIT for treating animals bearing H441 lung cancer cells. (A) NIR-PIT injection regimen. (B) In vivo fluorescence real-time imaging of tumor-bearing mice in response to NIR-PIT. The tumors treated by NIR-PIT represented a decrease in IR700 fluorescence after NIR-PIT. (C) Tumor growth was substantially reduced in the NIR-PIT treatment groups. (D) Significantly prolonged survival was observed in the NIR-PIT treatment group. Reproduced from [75].

Figure 5

Chemotherapeutic agent and PDT of NCP@pyrolipid induced ICD, which caused the release of tumor-associated antigens (TAAs). Combined with the PD-L1 antibody inhibitor, the NCP@pyrolipid chemotherapy/PDT significantly stimulated the generation of tumor-specific effector T cells and improved their infiltration in both primary and distant tumors, resulting in tumor removal in the primary sites and distant tumors. Reproduced from [87].

Figure 6

PEGylated doped- and undoped-TiO₂ nanoparticles for cancer-related PDT. Mode of the conjugation of NPs against the cytotoxicity on cervical cancer cells. Reproduced from [91].

Figure 7

Schematic illustrations of the process for synthesizing a biomimetic nanoreactor: (A) ROS generation based on chemiluminescence resonance energy transfer (CRET) with glucose consumption, no light excitation (B), and synergetic photodynamic-starvation therapy for metastases (C). Reproduced from [115].