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Induced Release of Nanocarrier Encapsulated Chemotherapeutic Drugs Using Proton Radiotherapy Beams

J Polf

J Polf1*, I Jackson1 , A Ranjan2 , Y Zheng3 , R Fernando2 , (1) University of Maryland School of Medicine, Baltimore, MD, (2) Oklahoma State University, Stillwater, OK, (3) Procure Proton Therapy Center, Oklahoma City, OK.


SU-E-T-211 Sunday 3:00PM - 6:00PM Room: Exhibit Hall

Purpose: The objectives of this study were to characterize: 1) the release of the drug doxorubicin (Dox) from low temperature sensitive liposomes (LTSLs) exposed to proton beam radiotherapy (PBRT) and 2) the resulting changes to the cell survival for PBRT irradiated cells due to the induced release of DOX.

Methods: Dox was actively loaded in LTSLs (Dox/LTSL). A549 adenocarcinoma cells were incubated with 200 nM of Dox/LTSL. Cell irradiations (0 to 6 Gy) were performed by placing the cell culture plates inside a solid water phantom using a 150 MeV clinical proton treatment beam. End points were survival fraction, radiation-mediated Dox release, and reactive oxygen species (ROS) production.

Results: The combination of the Dox/LTSL samples and PBRT achieved an additive synergistic response at various dose combinations. For PBRT doses < 3 Gy, the SF in the Dox/LTSL samples was similar to the SF values for PBRT only (no drug) samples. For PBRT doses > 3 Gy, the SF greatly decreases to a level similar to that of irradiated samples prepared with free DOX (no LTSL encapsulation). Studies of the DOX/LTSL samples indicated ~30% of the Dox was released from LTSLs and a 1.5 to 2 fold increase in ROS level occurred compared to control samples (LTSL alone) for PBRT doses > 3 Gy.

Conclusion: The combination of Dox/LTSLs and PBRT achieved additive cell killing in vitro at doses greater than 3 Gy. We hypothesize that PBRT may induce drug release from LTSLs for doses > 2Gy. These initial results show the potential for concurrent PBRT and Dox/LTSL treatment for targeted drug release only in the high dose regions (> 2 Gy), thus limiting the synergistic cytotoxic effects of concurrent PBRT DOX/LTSL therapy to the treatment volume and sparing surrounding healthy tissues (receiving lower doses) the effects of the drug.

Funding Support, Disclosures, and Conflict of Interest: Funding: Research Advisory Council Grant, Oklahoma State University Center for Veterinary Health Sciences

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