Current Targets and Bioconjugation Strategies in Photodynamic Diagnosis and Therapy of Cancer

Abstract

Photodynamic diagnosis (PDD) and therapy (PDT) are emerging, non/minimally invasive techniques for cancer diagnosis and treatment. Both techniques require a photosensitizer and light to visualize or destroy cancer cells. However, a limitation of conventional, non-targeted PDT is poor selectivity, causing side effects. The bioconjugation of a photosensitizer to a tumor-targeting molecule, such as an antibody or a ligand peptide, is a way to improve selectivity. The bioconjugation strategy can generate a tumor-targeting photosensitizer conjugate specific for cancer cells, or ideally, for multiple tumor compartments to improve selectivity and efficacy, such as cancer stem cells and tumor neovasculature within the tumor microenvironment. If successful, such targeted photosensitizer conjugates can also be used for specific visualization and detection of cancer cells and/or tumor angiogenesis (an early event in tumorigenesis) with the hope of an early diagnosis of cancer. The purpose of this review is to summarize some current promising target molecules, e.g., tissue factor (also known as CD142), and the currently used bioconjugation strategies in PDT and PDD, with a focus on newly developed protein photosensitizers. These are genetically engineered photosensitizers, with the possibility of generating a fusion protein photosensitizer by recombinant DNA technology for both PDT and PDD without the need of chemical conjugation. We believe that providing an overview of promising targets and bioconjugation strategies will aid in driving research in this field forward towards more effective, less toxic, and non- or minimally invasive treatment and diagnosis options for cancer patients.

Photodynamic Therapy: A Compendium of Latest Reviews

“…As was noted in Ref. [125], the bioconjugation follows a well-established strategy, consisting of chemical conjugation of a targeting molecule to a chemical PS (with direct or indirect linkage) or a bioconjugated organic PS (with a targeting peptide or antibodies), as seen in Figure 5. The molecule can be a peptide, a full length or partial sequence of a ligand (for a membrane-bound receptor), or a full-length antibody or antibody fragments (also called photoimmunoconjugates [126][127][128]).…”

“…The molecule can be a peptide, a full length or partial sequence of a ligand (for a membrane-bound receptor), or a full-length antibody or antibody fragments (also called photoimmunoconjugates [126][127][128]). An ideal tumour target molecule would be commonly expressed on several malignancy-related compartments in the tumour microenvironment, including, but not limited to, cancer cells, tumour vascular endothelial cells (VCEs), cancer stem cells, and myeloid-derived suppressor cells [125]. Alternatively, the use of nanotechnology in PDT has undergone exponential growth in the last decade (see Figure 1).…”

“…A potentially new bioconjugation strategy is the use of recombinant DNA techniques to produce fusion proteins that contain a targeting domain and a fluorescent protein PS simultaneously for targeted PD and PDT. Reproduced with permission from S. Gomez et al, Molecules; published by MDPI, 2020[125].…”

Development of Non-Porous Silica Nanoparticles towards Cancer Photo-Theranostics

“…In addition to imaging, the application of optics is also being expanded to therapeutic techniques, such as photodynamic therapy (PDT). PDT is a breakthrough medical technique which irradiates only the lesion area with an optical laser, in order to treat cancer without resorting to surgery, further reducing complications [ 32 , 33 ]. Recent research in nanomedicine has been progressing toward the realization of the integration of diagnosis and therapy, termed “theranostics”.…”

A Study on Mesoporous Silica Loaded With Novel Photosensitizers HCE6 and Oxaliplatin for the Treatment of Cholangiocarcinoma

“…It is favored by investigators because of its relatively few side effects and higher targeted treatment in relative to conventional chemoradiotherapy. Nevertheless, the fact that photosensitizers are highly hydrophobic makes their transport in patient more difficult, triggering certain limitations in PDT clinically ( 7 , 8 ). To address this situation, to improve the efficiency of drug delivery can has a positive impact on the anti-cancer effect of photosensitizers.…”