Nanoparticle delivery of chemotherapy combination regimen improves the therapeutic efficacy in mouse models of lung cancer

Jing Tian; Yuangzeng Min; Zachary Rodgers; Xiaomeng Wan; Hui Qiu; Yu Mi; Xi Tian; Kyle T. Wagner; Joseph M. Caster; Yanfei Qi; Kyle Roche; Tian Zhang; Jianjun Cheng; Andrew Z. Wang

doi:10.1016/j.nano.2016.11.007

Nanoparticle delivery of chemotherapy combination regimen improves the therapeutic efficacy in mouse models of lung cancer

Jing Tian, Yuangzeng Min, Zachary Rodgers, Xiaomeng Wan, Hui Qiu, Yu Mi, Xi Tian, Kyle T. Wagner, Joseph M. Caster, Yanfei Qi, Kyle Roche, Tian Zhang, Jianjun Cheng, Andrew Z. Wang

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	1301-1307
Number of pages	7
Journal	Nanomedicine: Nanotechnology, Biology, and Medicine
Volume	13
Issue number	3
DOIs	https://doi.org/10.1016/j.nano.2016.11.007
State	Published - Apr 1 2017
Externally published	Yes

Keywords

Cisplatin prodrugs
Combination therapy
Docetaxel
Drug delivery
PLGA–PEG

ASJC Scopus subject areas

Bioengineering
Medicine (miscellaneous)
Molecular Medicine
Biomedical Engineering
General Materials Science
Pharmaceutical Science

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10.1016/j.nano.2016.11.007

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Tian, J., Min, Y., Rodgers, Z., Wan, X., Qiu, H., Mi, Y., Tian, X., Wagner, K. T., Caster, J. M., Qi, Y., Roche, K., Zhang, T., Cheng, J., & Wang, A. Z. (2017). Nanoparticle delivery of chemotherapy combination regimen improves the therapeutic efficacy in mouse models of lung cancer. Nanomedicine: Nanotechnology, Biology, and Medicine, 13(3), 1301-1307. https://doi.org/10.1016/j.nano.2016.11.007

Tian, J, Min, Y, Rodgers, Z, Wan, X, Qiu, H, Mi, Y, Tian, X, Wagner, KT, Caster, JM, Qi, Y, Roche, K, Zhang, T, Cheng, J & Wang, AZ 2017, 'Nanoparticle delivery of chemotherapy combination regimen improves the therapeutic efficacy in mouse models of lung cancer', Nanomedicine: Nanotechnology, Biology, and Medicine, vol. 13, no. 3, pp. 1301-1307. https://doi.org/10.1016/j.nano.2016.11.007

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title = "Nanoparticle delivery of chemotherapy combination regimen improves the therapeutic efficacy in mouse models of lung cancer",

abstract = "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.",

keywords = "Cisplatin prodrugs, Combination therapy, Docetaxel, Drug delivery, PLGA–PEG",

author = "Jing Tian and Yuangzeng Min and Zachary Rodgers and Xiaomeng Wan and Hui Qiu and Yu Mi and Xi Tian and Wagner, {Kyle T.} and Caster, {Joseph M.} and Yanfei Qi and Kyle Roche and Tian Zhang and Jianjun Cheng and Wang, {Andrew Z.}",

note = "Funding Information: This work was supported by National Institutes of Health/National Cancer Institute (R01CA178748-01) and National Institutes of Health/National Cancer Institute (U54CA198999, Carolina Center of Cancer Nanotechnology Excellence (CCNE)-Nano Approaches to Modulate Host Cell Response for Cancer Therapy). Jing Tian is supported by the Natural Science Foundation of Tianjin (Grant No. 15JCYBJC21100) and the Science & Technology Development Fund of Tianjin Education Commission for Higher Education (No. 20110511). Zachary Rodgers is supported by the Carolina Cancer Nanotechnology T32 Training Program (C-CNTP, NIH-1T32CA196589). Andrew Wang was also supported by funding from the NIH/NCI (R21 CA182322). Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",

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AU - Tian, Jing

AU - Min, Yuangzeng

AU - Rodgers, Zachary

AU - Wan, Xiaomeng

AU - Qiu, Hui

AU - Mi, Yu

AU - Tian, Xi

AU - Wagner, Kyle T.

AU - Caster, Joseph M.

AU - Qi, Yanfei

AU - Roche, Kyle

AU - Zhang, Tian

AU - Cheng, Jianjun

AU - Wang, Andrew Z.

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N2 - 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.

AB - 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.

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Nanoparticle delivery of chemotherapy combination regimen improves the therapeutic efficacy in mouse models of lung cancer

Abstract

Keywords

ASJC Scopus subject areas

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