M Moreau¹³⁴*, G Richards¹⁵, S Yasmin-Karim¹², W Ngwa¹²³⁴, (1) Dana Farber Cancer Institute and Brigham and Womens Hospital, Boston, MA, (2) Harvard Medical School, Boston, MA, (3) University of Massachusetts Lowell, Lowell, MA, (4) Johns Hopkins University, Boston, MA, (5)Northeastern University, Boston, MA,

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  M Moreau

WE-B-BRC-4 (Wednesday, 7/13/2022) 8:30 AM - 9:30 AM [Eastern Time (GMT-4)]

Ballroom C

Purpose: Nanoparticle drones (smart nanomaterials) can now be constructed with capability to deliver therapeutic payloads and be activated with radiotherapy photons to release micrometer-range missile-like electrons or reactive oxygen species to destroy tumor cell. The purpose of this study is to investigate the potential of such nanoparticle drones to enhance image-guided radiotherapy.

Methods: A colloid of nanoparticle drones (nanodrones) was developed with ultrasmall Gadolinium nanoparticles incorporated in a mixture of natural polymers (chitosan and Alginic acid sodium salt from brown algae) and loaded with the therapeutic payload antiCD40. A second formulation was developed with titanium dioxide (TiO2) nanoparticles. Pancreatic cancer (KPC) cells (1.5x10^5 cells/mL) were used to generate subcutaneous tumors in C57BL6 mice (8– 10 weeks old). The nanodrone colloid was administered during image-guided radiotherapy with the small animal radiation research platform (SARRP) with one radiotherapy fraction treatment of 5 Gy to monitor movement of the nanoparticle drones through the tumors with MRI/CT imaging and assess therapeutic outcome. Results where compared to appropriate controls, including no treatment, radiotherapy alone, and no radiotherapy.

Results: Results showed that the nanoparticle drone distribution could be monitored over time by MRI or CT imaging in-vivo over 4-weeks as tumors responded to treatment. Results show the nanodrone colloid significantly slowed tumor growth and prolonged mice survival (p < 0.0001) over time.

Conclusion: The results highlight the potential of nanoparticle drones for enhancing image-guided radiotherapy. The potential to load different therapeutic payloads and provide image contrast highlight great potential for using such technology for combining image-guided radiotherapy with chemotherapy or immunotherapy.

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