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Updated: Oct 3, 2025
Near Infrared Photoimmunotherapy for Mouse Models of Pleural Dissemination
Published on: February 9, 2021
Antibody guided activatable NIR photosensitizing system for fluorescently monitored photodynamic therapy with reduced
Ebaston Thankarajan1, Helena Tuchinsky2, Sarit Aviel-Ronen3
1Department of Chemical Sciences, the Faculty of Natural Sciences, Ariel University, Ariel 40700, Israel.
Abstract:
Photodynamic therapy (PDT) utilizing an organic dye (photosensitizer) capable of killing cancer cells in the body upon light irradiation is one of the promising non-invasive treatment modalities for many cancers. A known drawback of PDT is a side-effect caused by existing photosensitizers to organs due to insufficient specificity and accidental light exposure of a patient during the delivery of the photosensitizer in the bloodstream. To overcome this issue, we developed a novel antibody guided, activatable photosensitizing system, Ab-mI2XCy-Ac, where the trastuzumab (Ab) is linked to the non-active (not phototoxic and not fluorescent) dye, mI2XCy-Ac, that contains the hydroxyl group protected by acetyl (Ac). This targeting, non-photo-active conjugate was shown to be safely (without detectable side-effects) delivered to the targeted tumor, where it is activated by the esterase-mediated acetyl group cleavage and effectively treats the tumor upon NIR light irradiation. It was demonstrated in the Her2 positive BT-474 tumor mouse model that the treatment efficacy of the activatable photosensitizing system is about the same as for the permanently active photosensitizer, Ab-mI2XCy, while the side-effects are noticeably reduced. In addition, this activatable system enables fluorescence monitoring of the photosensitizer activation events.
Insights
A new antibody-guided photosensitizer system targets cancer cells, activating only at the tumor site. This reduces side effects compared to traditional photodynamic therapy (PDT), enabling safer and effective non-invasive cancer treatment.
Area of Science:
- Biomedical Engineering
- Oncology
- Photochemistry
Background:
- Photodynamic therapy (PDT) offers non-invasive cancer treatment using photosensitizers activated by light.
- Current PDT faces challenges with photosensitizer specificity, leading to side effects from off-target organ exposure and accidental light activation.
Purpose of the Study:
- To develop a novel antibody-guided, activatable photosensitizing system to enhance PDT specificity and reduce side effects.
- To evaluate the safety, efficacy, and activation monitoring capabilities of the new system in a preclinical cancer model.
Main Methods:
- Development of an activatable photosensitizer (Ab-mI2XCy-Ac) by linking trastuzumab (Ab) to a non-phototoxic dye with a protected hydroxyl group.
- In vivo testing in a Her2-positive BT-474 tumor mouse model to assess delivery, activation, efficacy, and side effects.
- Utilized esterase-mediated cleavage for in-situ activation and fluorescence monitoring of photosensitizer activation.
Main Results:
- The antibody-guided, activatable photosensitizer system (Ab-mI2XCy-Ac) was safely delivered to tumors with no detectable side effects.
- The system demonstrated comparable tumor treatment efficacy to a permanently active photosensitizer (Ab-mI2XCy) but with significantly reduced side effects.
- The activatable system allowed for fluorescence monitoring of photosensitizer activation events within the tumor.
Conclusions:
- The novel antibody-guided, activatable photosensitizing system represents a significant advancement in PDT, offering targeted cancer cell killing with improved safety.
- This approach overcomes key limitations of traditional PDT by minimizing off-target toxicity and enabling real-time monitoring of treatment activation.
- The developed system holds promise for more effective and safer non-invasive cancer therapies.
