In vitro study of radiosensitization of PLGA-SPION nanoparticles loaded with Gemcitabine

Introduction: To increase the radiation therapy efficiency, two approaches have been employed which include increasing the dose delivery or modifying the biological response to ionizing radiation. This study aimed to modify the biological response to ionizing radiation by combination therapy using radio-sensitizer agent and anticancer drug. Materials and Methods: In order to achieve this aim, super paramagnetic iron oxide nanoparticles (SPIONs) were prepared and used simultaneously with gemcitabine (Gem) as a chemotherapeutic drug. These two agents were encapsulated simultaneously in PLGA to form multifunctional drug delivery system. The physicochemical characteristics of the nanoparticles including particle size distribution, morphology, encapsulation efficiency and in vitro release were studied. The dose enhancement ratio (DER) of gemcitabine hydrochloride as well as PLGA-Gem, PLGA- SPION and PLGA-SPION-Gem nanoparticles were calculated and compared in human breast cancer cell line (MCF-۷). Results: The PLGA-SPION-Gem nanoparticles exhibited narrow size distribution with spherical shape. The hydrodynamic diameters of nanoparticles were between ۱۷۰ to ۱۸۰ nm. Gemcitabine and SPION encapsulation efficiency were between ۱۳.۲% to ۱۶.۱% and ۴۸.۲% to ۵۰.۱%, respectively. In vitro gemcitabine release kinetics study showed a controlled behavior. The dose enhancement ratio for Gem, PLGA-Gem, PLGA-SPION and PLGA-SPION- Gem was the highest at ۱ Gy ۶۰Co and were ۱.۰۴, ۱.۶۳, ۲.۳۴ and ۳.۱۸, respectively. The radio sensitization of PLGA-SPION-Gem nanoparticles indicated a more significant radio sensitization activity compared with either other nanoparticles or gemcitabine alone (p≤۰.۰۰۱).   Conclusion: We have successfully developed a gemcitabine and SPION-loaded PLGA with multifunctional drug delivery system for radiosensitization in radiotherapy. Future work includes in-vivo investigation of radiosensitization and other application of these nanoparticles.