期刊
MOLECULAR PHARMACEUTICS
卷 14, 期 12, 页码 4551-4559出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.7b00669
关键词
nanoparticles; sequential delivery; controlled delivery; combination therapy; EGFR inhibitor; doxorubicin
资金
- Marlene Harris-Ride Cincinnati Breast Cancer Foundation
There are an increasing number of studies showing the order of drug presentation plays a critical role in achieving optimal combination therapy. Here, a nanoparticle design is presented using ion pairing and drug-polymer conjugate for the sequential delivery of gefitinib (Gi) and doxorubicin (Dox) targeting epidermal growth factor receptor (EGFR) signaling applicable for the treatment of triple negative breast cancers. To realize this nanoparticle design, Gi complexed with dioleoyl phosphatidic acid (DOPA) via ion paring was loaded onto the nanoparticle made of Dox-conjugated poly(L-lactide)block-polyethylene glycol (PLA-b-PEG) and with an encapsulation efficiency of,90%. The nanoparticle system exhibited a desired sequential release of Gi followed by Dox, as verified through release and cellular uptake studies. The nanoparticle system demonstrated approximate 4-fold and 3-fold increases in anticancer efficacy compared to a control group of Dox PLAPEG conjugate against MDA-MB-468 and A549 cell lines in terms of half maximal inhibitory concentration (IC50), respectively. High tumor accumulation of the nanoparticle system was also substantiated for potential in vivo applicability by noninvasive fluorescent imaging.
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