Radiosensitizationeffect and Therapeutic Benefits of Small Sized Gold Nanoparticles
S Yasmin-Karim1Brigham and Women's Hospital, U Ibeh2, M Moreau3*, N Bih4, U Ngwa5, B Ziberi6, R Kumar7, G Makrigiorgos8, W Ngwa9, (1) Brigham and Women's Hospital, Boston, MA, (2) University of Massachusetts Boston, Boston, MA, (3) Johns Hopkins University, Columbia, MD, (4) Johns Hopkins University, Boston, MA, (5) Libertas Scholars Inc, ,,(6) University of Tetova, Tetova, Republic of North Macedonia, Boston, MA, (7) West Pharmaceutical Services, Inc., ,,(8) Dana Farber Cancer Institute, Boston, MA, (9) Johns Hopkins University, Boston, MA
Presentations
TU-D1030-IePD-F4-1 (Tuesday, 7/12/2022) 10:30 AM - 11:00 AM [Eastern Time (GMT-4)]
Exhibit Hall | Forum 4
Purpose: Nanotechnology-aided radiotherapy is an emerging technique for increasing cancer cell radiosensitivity and improving cellular targeting. Metallic nanoparticles - gold nanoparticles have begun to play an increasingly important role in the field of nanotechnology and cancer biology due to their ability to generate free radicals through the Photoelectric and Auger effect. Nanoparticle size plays a vital role in the cellular uptake, drug release kinetics, biodistribution, and toxicity of nanomaterials. Macrophage engulfment of nanomaterials is also dependent on particle size, and they can only recognize relatively larger nanoparticles. Cognizant of these, this work is an in-vitro and in-vivo investigation of the effect of small-sized gold nanoparticles (GNPs) on cancer epithelial and endothelial cells during radiation therapy.
Methods: GNPs were synthesized in ultra-small size, (> 5 nm in diameter) based on previously optimized protocols using Tetrakis (Hydroxymethyl) Phosphonium Chloride (THPC) as a reducing/capping agent. Synthesized nanoparticles were PEGylated using heterobifunctional PEG (thiol-PEG-amine). Fluorophore Alexafluor 647 (AF647) were conjugated to the amine groups of the PEG. Human prostate (PC-3, ATCC) and mouse prostate (TRAMP-C1, ATCC), Human Choroidal Endothelial cells (HCEC, Celprogen), Human umbilical vein endothelial cells (HUVEC, LONZA) were analyzed. All cells were cultured maintaining the respective protocol suggested by the company. Syngeneic prostate tumor models were generated in wild (+/+) C57/BL6 background mice (Tachonoc Mice). All radiation treatments were given by SARRP.
Results: Our in-vitro study shows enhancement of the radiation effect in human prostate cancer (PC3) and in endothelial (HCEC and HUVEC) cell lines using small sized pegGNPs. Subsequent in-vivo study also demonstrates enhancement of the survival duration (p<0.01) when using image guided radiotherapy (5 Gy) with intra-tumoral Anti-CD40 (20 µg)+ pegGNP (1.15 µg) treatment.
Conclusion: Overall pegGNPs demonstrates significant enhancement of the radiation treatment to both prostate cancer and endothelial cells serving as neovascular age-related macular degeneration treatment models.
Keywords
Radiation Therapy, Blood Vessels, Radioimmunotherapy
Taxonomy
TH- Radiobiology(RBio)/Biology(Bio): Bio- tissue and microenvironment
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