Title |
Cooperation of IRAK1/4 inhibitor and ABT-737 in nanoparticles for synergistic therapy of T cell acute lymphoblastic leukemia
|
---|---|
Published in |
International Journal of Nanomedicine, October 2017
|
DOI | 10.2147/ijn.s146875 |
Pubmed ID | |
Authors |
Xiaoyan Wu, Lin Wang, Yining Qiu, Bingyu Zhang, Zhenhua Hu, Runming Jin |
Abstract |
T cell acute lymphoblastic leukemia (T-ALL) is caused by clonal expansion of variant T cell progenitors and is considered as a high risk leukemia. Contemporary single chemotherapy has a limited effect due to dynamic and versatile properties of T-ALL. Here IRAK1/4 inhibitor and ABT-737 were co-encapsulated into polyethylene glycol modified poly (lactic-co-glycolic acid) nanoparticles (IRAK/ABT-NP) to enhance synergistic therapy of T-ALL. The formulation was optimized to achieve high drug loading using Box-Behnken design and response surface methodology. The optimal parameter comprised 2.98% polymer in acetonitrile, a ratio of oil phase to water phase of 1:8.33, and 2.12% emulsifier concentration. High drug loading and uniform spherical shape was achieved. In vitro release study showed sustained release of IRAK1/4 inhibitor for 72 hours as well as sustained release of ABT-737 for more than 120 hours. Uptake efficiency of IRAK/ABT-NP and induced apoptotic T-ALL fraction by IRAK/ABT-NP were much higher than the IRAK1/4 and ABT-737 combined solution. IC50 of IRAK/ABT-NP was two-fold lower than free drug combination in Jurkat cells. Additionally, we conducted in vivo experiments in which IRAK/ABT-NP exhibited greater cytotoxicity toward T-ALL cells, the capacity to significantly restore white blood cell number in peripheral blood, and improved survival time of T-ALL mouse model compared to the IRAK1/4 and ABT-737 combined solution. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 28 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 7 | 25% |
Student > Master | 4 | 14% |
Student > Bachelor | 3 | 11% |
Other | 2 | 7% |
Researcher | 2 | 7% |
Other | 4 | 14% |
Unknown | 6 | 21% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 4 | 14% |
Pharmacology, Toxicology and Pharmaceutical Science | 3 | 11% |
Engineering | 3 | 11% |
Biochemistry, Genetics and Molecular Biology | 2 | 7% |
Agricultural and Biological Sciences | 1 | 4% |
Other | 6 | 21% |
Unknown | 9 | 32% |