June 20, 2024
Targeted Nanotherapy

Targeted Nanotherapy: Advancing Fluorescence-Guided Photoimmunotherapy for Peritoneal Carcinomatosis

A team of researchers from the University of Maryland, Harvard Medical School, and the Modulight Corporation in Finland has made significant advancements in the field of fluorescence-guided intervention strategies for the detection and treatment of microscopic tumors. Their work, published in Science Advances, focuses on the integration of three technical innovations to improve photoimmunotherapy and nanotechnology for targeted cancer treatment.

The researchers developed a photoactivatable multiagent liposome, a nanoliposome labeled with fluorophores that can track and sensitize immunoconjugates for photoimmunotherapy. They conducted experiments using fluorescence-guided drug delivery and fluorescence-guided light dosimetry to study the effects on peritoneal carcinomatosis in mouse models.

The results of their research showed that the targeted photoactivatable multiagent liposome enhanced drug delivery to metastases by 14-fold. By combining intervention methods, the researchers were able to vary the treatment response for tumor control without side effects.

One application of this technology is in the treatment of ovarian cancer, particularly in cases of peritoneal metastasis or incomplete resection and drug resistance. These factors can make advanced ovarian cancer nearly incurable with existing surgical and chemotherapy approaches. The integration of targeted therapy, imaging, and monitoring can address drug-resistant micro-metastases and improve treatment outcomes.

Intraoperative photodynamic therapy using non-targeted photosensitizers has been used for peritoneal carcinomatosis, but its effectiveness has been limited by tumor heterogeneity and a lack of specificity during the uptake of photosensitizer. The researchers addressed these limitations by developing targeted photoactivatable multiagent liposomes (TPMAL) for photochemotherapy. These liposomes were engineered with molecular targeting and fluorescence-tracking features and combined with a laser endoscopy system for safe and customized drug delivery.

To activate photoimmunotherapy, the researchers attached photosensitizer molecules to anti-epidermal growth factor receptor monoclonal antibodies using carbodiimide chemistry. They then linked this to the nanoliposomes using click chemistry to create targeted photoactivatable multilayer liposomes. In vivo experiments in mice showed enhanced tumor selectivity and retention capacity.

The researchers also studied the biodistribution of the photosensitizer immunoconjugate-nanoliposome-carboxyfluorescein compounds, tracking their fluorescence signals to indicate their capacity to lock in and co-deliver drugs to target sites. They found increased accumulation of the compound in metastatic tumors compared to normal tissues, making it a promising treatment strategy for peritoneal carcinomatosis.

This research opens up new possibilities for the use of photodynamic therapy in the treatment of peritoneal carcinomatosis, particularly in cases of ovarian cancer. With a high percentage of ovarian cancer patients being diagnosed in advanced stages, there is a need for more effective treatment options to improve survival rates. Photoimmunotherapy, with its targeted approach and ability to activate immune responses, shows great potential in this regard.

The development of cancer-targeted photoactivated multiagent liposomes allows for the co-delivery of photosensitive immunoconjugates and chemotherapy drugs, providing insights into the mechanisms of antitumor immune responses and improving drug delivery for effective cancer treatment.

Overall, this research represents a significant advancement in the field of nanotherapy and fluorescence-guided photoimmunotherapy. By improving targeted drug delivery and treatment response variability, this technology has the potential to greatly enhance the management of peritoneal carcinomatosis and ultimately improve patient outcomes.

1. Source: Coherent Market Insights, Public sources, Desk research
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