Photodynamic Therapy: Targeting Cancer Biomarkers for the Treatment of Cancers

Abstract

Photodynamic therapy (PDT) is a well-documented therapy that has emerged as an effective treatment modality of cancers. PDT utilizes harmless light to activate non- or minimally toxic photosensitizers to generate cytotoxic species for malignant cell eradication. Compared with conventional chemotherapy and radiotherapy, PDT is appealing by virtue of the minimal invasiveness, its safety, as well as its selectivity, and the fact that it can induce an immune response. Although local illumination of the cancer lesions renders intrinsic selectivity of PDT, most photosensitizers used in PDT do not display significant tumor tissue selectivity. There is a need for targeted delivery of photosensitizers. The molecular identification of cancer antigens has opened new possibilities for the development of effective targeted therapy for cancer patients. This review provides a brief overview of recent achievements of targeted delivery of photosensitizers to cancer cells by targeting well-established cancer biomarkers. Overall, targeted PDT offers enhanced intracellular accumulation of the photosensitizer, leading to improved PDT efficacy and reduced toxicity to normal tissues.

Keywords: antibodies; ligands; photodynamic therapy; photosensitizer; targeted therapy.

Figure 1

Modified Jablonski scheme illustrating the principles and mechanisms of photodynamic therapy. Reprinted with permission from Ref. [8]. Copyright 2006 Springer Nature.

Figure 2

Structures of some photosensitizers and protoporphyrin IX precursor 5-ALA.

Figure 3

(a) General structure of antibody-based IR700 conjugates for NIR-PIT. (b) Pan-IR700 selectively accumulate in EGFR-expressing A431 tumors (right), but not in EGFR-non-expressing 3T3 tumors (left). (c) PIT with Pan-IR700 significantly inhibited A431 tumor growth. (d) PIT with Pan-IR700 significantly prolonged animal survival time. (***: p < 0.001). Reprinted with permission from Ref. [62]. Copyright 2011 Springer Nature.

Figure 4

Comparison of full-length antibodies (IgG), minibodies, diabodies, and affibodies. Reprinted with permission from Ref. [85]. Copyright 2018 Chemistry Europe.

Figure 5

(a) Phototoxicity of GO–FA–ZnO. (b) Hypothetical mechanism of GO–FA–ZnO-induced PDT. Reprinted with permission from Ref. [96]. Copyright 2013 Royal Society of Chemistry.

Figure 6

(a) Comparison of fluorescence images of mice received PSMA-targeting AuNPs-Pc158 and PSMA-1-Pc413 before and after each PDT. (b) Normalized fluorescence intensity of PSMA-targeting AuNPs-Pc158 and PSMA-1-Pc413. (c) Illustration of lysosome release of Pc158 by cathepsin and accumulation of Pc158 into mitochondria. (d) Multiple PDT with PSMA-targeting AuNPs-Pc158 effectively inhibits large tumor (>500 mm³) growth. Reprinted with permission from Ref. [123]. Copyright 2020 American Chemical Society.

Figure 7

(a) Fluorescence images of mice bearing U87MG tumors after injected with arginine-glycine-aspartate peptide (RGD) modified IR700-polymers. (b) Confocal images showing intratumor distribution of photosensitizers. (c) In vivo PDT of mice bearing U87MG. Reprinted with permission from Ref. [137]. Copyright 2018 Springer Nature.