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Highly versatile cancer photoimmunotherapy using photosensitizer-conjugated avidin and biotin-conjugated targeting antibodies.

ABSTRACT: Background:Photoimmunotherapy (PIT) employing antibody-photosensitizer conjugates is a promising treatment for cancer. However, the fixed antigen specificity severely limits the efficacy and the applicability. Here we describe a universal strategy for PIT of cancer by using a near-infrared (NIR) photosensitizer IRDye700DX-conjugated NeutrAvidin, designated as AvIR, together with various biotinylated antibodies (BioAbs) for cellular targeting. Methods:Cytotoxicity of AvIR-mediated PIT was evaluated by fluorescence imaging and cell viability assay. Phototoxic effect on tumorigenicity was assessed by tumorsphere-formation assay and Matrigel invasion assay. Cancer stem cell-like side-population (SP) cells were identified by flow cytometry. Results:CHO cells stably expressing carcinoembryonic antigen or EpCAM were pre-labeled with each BioAb for the corresponding antigen, followed by AvIR administration. NIR light irradiation specifically killed the targeted cells, but not off-targets, demonstrating that the AvIR-mediated PIT does work as expected. CSC-like subpopulation of MCF-7 cells (CD24low/CD44high) and SP of HuH-7 cells (CD133+/EpCAM+) were effectively targeted and photokilled by AvIR-PIT with anti-CD44 BioAb or anti-CD133/anti-EpCAM BioAbs, respectively. As results, the neoplastic features of the cell lines were sufficiently suppressed. Cancer-associated fibroblast (CAF)-targeted AvIR-PIT by using anti-fibroblast activation protein BioAb showed an abolishment of CAF-enhanced clonogenicity of MCF-7 cells. Conclusions:Collectively, our results demonstrate that AvIR-mediated PIT can greatly broaden the applicable range of target specificity, with feasibility of efficacious and integrative control of CSC and its microenvironment.

SUBMITTER: Shirasu N

PROVIDER: S-EPMC6858743 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Highly versatile cancer photoimmunotherapy using photosensitizer-conjugated avidin and biotin-conjugated targeting antibodies.

Shirasu Naoto N Shibaguchi Hirotomo H Yamada Hiromi H Kuroki Masahide M Yasunaga Shin'ichiro S

Cancer cell international 20191115

<h4>Background</h4>Photoimmunotherapy (PIT) employing antibody-photosensitizer conjugates is a promising treatment for cancer. However, the fixed antigen specificity severely limits the efficacy and the applicability. Here we describe a universal strategy for PIT of cancer by using a near-infrared (NIR) photosensitizer IRDye700DX-conjugated NeutrAvidin, designated as AvIR, together with various biotinylated antibodies (BioAbs) for cellular targeting.<h4>Methods</h4>Cytotoxicity of AvIR-mediated ...[more]

PMID: 31787847

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Project description:Affinity interactions between the small molecule biotin and the protein avidin have been used extensively to functionalize biomaterials. More recently, researchers have leveraged the changes in biotin-avidin affinity that occur upon biotin conjugation to larger molecules to control the release of biotinylated drugs and proteins. However, the effects of biotin-avidin interactions on hydrogel properties have not been thoroughly investigated. The objective of this study was to evaluate the effect of increasing biotin and avidin concentrations on hydrogel swelling properties, as an indicator of crosslinking. Gelatin, selected as a model hydrogel material, was biotinylated at increasing fold molar excesses of biotin with a PEG linker using N-hydroxysuccinimide chemistry. Afterwards, biotinylated gelatin was formed into hydrogels and stabilized with glutaraldehyde. Swelling properties of the biotinylated hydrogels were investigated by conducting swelling studies in different avidin solutions. Increasing the degree of biotinylation caused significant decreases in swelling ratios of the hydrogels in a dose-dependent manner, suggesting increases in crosslinking of the hydrogels. However, increasing avidin concentrations in excess of biotin content did not significantly affect swelling ratios. Moving hydrogels to phosphate-buffered saline following avidin incorporation resulted in increased swelling ratios for hydrogels prepared with a lower concentration of biotin. However, hydrogels prepared with the highest concentration of biotin did not experience increased swelling ratios, implying that the stability of biotin-avidin-mediated crosslinking depends on the number of biotin molecules available for binding. Collectively, these results demonstrate that biotin-avidin interactions control hydrogel swelling properties, and that the magnitude and stability of the effects depend on the biotin concentration. These results have important implications for affinity-based controlled release of biotinylated drugs or proteins from biotin-avidin-crosslinked hydrogels.

Dataset Information

Highly versatile cancer photoimmunotherapy using photosensitizer-conjugated avidin and biotin-conjugated targeting antibodies.

Publications

Highly versatile cancer photoimmunotherapy using photosensitizer-conjugated avidin and biotin-conjugated targeting antibodies.

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