Journal
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
Volume 13, Issue 3, Pages 1301-1307Publisher
ELSEVIER
DOI: 10.1016/j.nano.2016.11.007
Keywords
Drug delivery; PLGA-PEG; Cisplatin prodrugs; Docetaxel; Combination therapy
Funding
- National Institutes of Health/National Cancer Institute [R01CA178748-01, U54CA198999]
- Natural Science Foundation of Tianjin [15JCYBJC21100]
- Science & Technology Development Fund of Tianjin Education Commission [20110511]
- Carolina Cancer Nanotechnology T32 Training Program (C-CNTP ) [NIH-1T32CA196589]
- NIH/NCI [R21 CA182322]
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The combination chemotherapy regimen of cisplatin (CP) and docetaxel (DTX) is effective against a variety of cancers. However, combination therapies present unique challenges that can complicate clinical application, such as increases in toxicity and imprecise exposure of tumors to specific drug ratios that can produce treatment resistance. Drug co-encapsulation within a single nanoparticle (NP) formulation can overcome these challenges and further improve combinations' therapeutic index. In this report, we employ a CP prodrug (CPP) strategy to formulate poly(lactic-co-glycolic acid)-poly(ethylene glycol) (PLGA-PEG) NPs carrying both CPP and DTX. The dually loaded NPs display differences in drug release kinetics and in vitro cytotoxicity based on the structure of the chosen CPP. Furthermore, NPs containing both drugs showed a significant improvement in treatment efficacy versus the free drug combination in vivo. (C) 2016 Elsevier Inc. All rights reserved.
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