期刊
ACS APPLIED MATERIALS & INTERFACES
卷 13, 期 9, 页码 10812-10821出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.1c02316
关键词
combination therapy; photodynamic therapy; nanoparticle; tirapazamine; drug delivery
资金
- Basic Research Program through the National Research Foundation of Korea (NRF) - Korean government (Ministry of Science, ICT, and Future Planning) [2016R1C1B3013951]
This study developed nanoparticles containing Pba and TPZ for combination therapy, successfully suppressing tumor growth in vivo through the synergetic effects and efficient drug delivery. The results suggest that in vitro screening based on CI values, mechanism studies, and real-time in vivo imaging are promising strategies for developing optimized combination therapy nanoparticles.
In combination therapy, synergetic effects of drugs and their efficient delivery are essential. Herein, we screened 12 anticancer drugs for combination with photodynamic therapy (PDT) using pheophorbide a (Pba). On the basis of combination index (CI) values in cell viability tests, we selected tirapazamine (TPZ) and developed self-assembled gelatin nanoparticles (NPs) containing both Pba and TPZ. The resulting TPZ-Pba-NPs showed a synergetic effect to kill tumor cells because TPZ was activated under the hypoxic conditions that originated from the PDT with Pba and laser irradiation. After they were injected into tumor-bearing mice via the tail vein, TPZ-Pba-NPs showed 3.17-fold higher blood concentration and 4.12-fold higher accumulation in tumor tissue 3 and 24 h postinjection, respectively. Upon laser irradiation to tumor tissue, TPZ-Pba-NPs successfully suppressed tumor growth by efficient drug delivery and synergetic effects in vivo. These overall results suggest that in vitro screening of drugs based on CI values, mechanism studies in hypoxia, and real-time in vivo imaging are promising strategies in developing NPs for optimized combination therapy.
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