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Alkaline Smart Radiotherapy Biomaterials to Overcome Acidic Tumor Microenvironment

M Moreau1*, Z Bashkim2 , W Ngwa3 , (1) Dana Farber Cancer Institute/University of Massachusetts Lowell, Boston, MA, (2) Dana Farber Cancer Institute, Boston, MA, (3) Harvard Medical School, Boston, MA


(Sunday, 7/14/2019)  

Room: ePoster Forums

Purpose: It has been reported in published manuscript that acidic pH mimicking tumor pH levels causes alterable anergy in both human and mouse CD8+ T lymphocytes in vitro. The hypothesis of this study is to introduce an alkaline agent such as smart radiotherapy biomaterials (a-SRBs) to cause apoptosis in tumor cells.

Methods: Optimal release kinetics of drugs from SRBs was monitored by varying: radiation (RT) dose, types of polymers used, and pH level of media to enhance therapeutic outcomes. SRB matrices were developed respectively as high-capacity payload poly-(lactic-co-glycolic)-acid (PLGA) and Polycaprolactone (PCL) 4mm-length spacers loaded with 5ug Fluorescein (FITC) dye to slowly release the drug-depot for simultaneous localized radiotherapy. FITC_SRBs were placed in varying pH of PBS media (e.g. pH 7.4, 6.8, and 8) to examine the effect of media pH on the SRBs. A comparison of PLGA and PCL SRB_FITC release kinetics was performed.

Results: Results show at RT doses of 6 and 20Gy, acidic media degrades SRBs faster than alkaline media. At 12Gy, PLGA_SRBs showed up to 59% higher release at pH 8 compared to pH 7.4. Results showed higher than 50% payload release for all RT doses at pH 8. PLGA_SRBs released faster than PCL_SRBs over 15-day span.

Conclusion: These results confirm that acidic medium mimicking the tumor microenvironment boosts the release of drugs from SRBs. These findings showed differing pH can influence the release of payload from SRBs. Therefore, further studies could investigate how alkaline SRBs (a-SRBs) can intensify the therapeutic efficiency of T-cell based immunotherapies.




TH- Small Animal RT: Development (new technology and techniques)

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