A photoactivatable antibody–Chlorin e6 conjugate enabling singlet oxygen production for tumor-targeting photodynamic therapy

Abstract

Photodynamic therapy is a new technology for disease diagnosis and treatment in modern medical clinics. The main advantages of photodynamic therapy are low toxicity and side effects, a wide range of applications, no drug resistance, and no obvious trauma in the treatment process. However, to achieve effective photodynamic therapy, new photosensitizer carriers need to be constructed, which can selectively deliver photosensitizers into tumor tissues. In this work, a photoactivatable antibody–Chlorin e6 conjugate with a dual-function to target tumor tissue and realize cancer photodynamic therapy is constructed. Both in vitro and in vivo experiments indicate that the antibody–Chlorin e6 conjugate has the ability to target tumors rapidly and efficiently, and has the ability to generate reactive oxygen species and kill tumor cells. Overall, this photoactivable antibody–Chlorin e6 conjugate may provide a promising strategy to address the current challenges of cancer photodynamic therapy.

A Photoactive Supramolecular Complex Targeting PD-L1 Reveals a Weak Correlation between Photoactivation Efficiency and Receptor Expression Levels in Non-Small-Cell Lung Cancer Tumor Models

“…Preliminary tests using sub-micromolar concentrations resulted in no significant effects and are not reported. This is in line with previously published works, where Atezolizumab [36,37] was used in definitely larger concentrations than the dissociation constant of the antibody, 0.19 nM and 0.62 nM for the dimeric and monomeric form of PD-L1, respectively [35].…”

“…The ATP assay performed 3 and 24 h after illumination (Figure 3E) and the MTT assay (Figure 3F) suggested that the photoinactivation was a little more efficient in A549 than in H322 cells when the conjugate was used at 5 µM, while the effect was comparable between the two models at 10 µM, within the error bars. Similar results were reported by Pan et al using a Chlorin-e6-functionalized Atezolizumab at the same concentrations on HCT-116 cells [36].…”

“…Atezolizumab, with durvalumab and avelumab, is one of the three anti-PD-L1 monoclonal antibodies approved by the FDA and is employed in the treatment of urothelial carcinoma, non-small-cell lung cancer (NSCLC), small-cell lung cancer, triple-negative breast cancer, hepatocellular carcinoma, and melanoma [ 35 ]. It has been applied in photo-immunotherapy only in one case so far, in combination with a different photosensitizer (Chlorin e6) on HCT-116, a colon cancer cellular line, demonstrating a decrease in the tumor mass larger than 50% in a mouse model upon illumination in comparison to dark conditions [ 36 ]. Moreover, it has been used in the intracellular light-controlled drug delivery method termed photochemical internalization, an innovative procedure to release a drug caged in endo/lysosomal compartments, exploiting the oxidative action of a photosensitizer (TPCS 2a /fimaporfin) upon irradiation [ 37 ].…”

Anti-PD-L1 immunoconjugates for cancer therapy: Are available antibodies good carriers for toxic payload delivering?

“…The conjugate demonstrated anti-tumor efficacy in HCT-116 (colon cancer cell line) tumor-bearing mouse model showing a tumor mass reduction greater than 50% compared to the same conjugate treatment without light activation. No data about the conjugate adverse effects in vivo were reported ( Pan et al, 2021 ).…”

Mitochondria-Targeted Nanomedicine for Enhanced Efficacy of Cancer Therapy

“…In addition to the passive accumulation, nanoparticles with active targeting performance are also employed to deliver drugs, by modifying specific ligands with high affinity to cancer cells ( e.g. polypeptides ( Fang et al, 2020 ; Kang et al, 2020 ), proteins, antibodies ( Chen et al, 2012 ; Pan et al, 2021 ), folic acids ( Mitra et al, 2018 ) and aptamers ( Tang et al, 2020 ; Tian et al, 2021 )). On this basis, the unique advantages of nanocarriers have been widely demonstrated including long-term sustained ( Xia et al, 2019 ) and controlled release ( Xia et al, 2014 ) and the integration with more diagnostic or therapeutic modality such as multimodal imaging ( Gao et al, 2017 ; Xia et al, 2017 ; Liu et al, 2019 ), photodynamic therapy (PDT) ( Lucky et al, 2015 ; Wen et al, 2020 ), photothermal therapy (PTT) ( Xia et al, 2016 ; Yang et al, 2017 ) and immunotherapy ( Meraz et al, 2012 ; Secret et al, 2013 ).…”