Nanodiamond Therapeutic Delivery Agents Mediate Enhanced Chemoresistant Tumor Treatment

被引:463
作者
Chow, Edward K. [2 ]
Zhang, Xue-Qing [1 ]
Chen, Mark [3 ,4 ]
Lam, Robert [5 ]
Robinson, Erik [5 ]
Huang, Houjin [5 ]
Schaffer, Daniel [1 ]
Osawa, Eiji [6 ]
Goga, Andrei [7 ]
Ho, Dean [1 ,5 ,8 ]
机构
[1] Northwestern Univ, Dept Biomed Engn, Evanston, IL 60208 USA
[2] Univ Calif San Francisco, George Williams Hooper Fdn, San Francisco, CA 94143 USA
[3] Northwestern Univ, Dept Biol Sci, Evanston, IL 60208 USA
[4] Northwestern Univ, Dept Chem, Evanston, IL 60208 USA
[5] Northwestern Univ, Dept Mech Engn, Evanston, IL 60208 USA
[6] Shinshu Univ, NanoCarbon Res Inst, Nagano 3868567, Japan
[7] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA
[8] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA
基金
美国国家科学基金会;
关键词
CARBON NANOTUBES; HEPATOCELLULAR-CARCINOMA; DETONATION NANODIAMOND; DIAMOND NANOPARTICLES; MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN; CANCER-THERAPY; CLINICAL-TRIAL; DRUG-DELIVERY; BREAST-CANCER;
D O I
10.1126/scitranslmed.3001713
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Enhancing chemotherapeutic efficiency through improved drug delivery would facilitate treatment of chemoresistant cancers, such as recurrent mammary tumors and liver cancer. One way to improve drug delivery is through the use of nanodiamond (ND) therapies, which are both scalable and biocompatible. Here, we examined the efficacy of an ND-conjugated chemotherapeutic in mouse models of liver and mammary cancer. A complex (NDX) of ND and doxorubicin (Dox) overcame drug efflux and significantly increased apoptosis and tumor growth inhibition beyond conventional Dox treatment in both murine liver tumor and mammary carcinoma models. Unmodified Dox treatment represents the clinical standard for most cancer treatment regimens, and NDX had significantly decreased toxicity in vivo compared to standard Dox treatment. Thus, ND-conjugated chemotherapy represents a promising, biocompatible strategy for overcoming chemoresistance and enhancing chemotherapy efficacy and safety.
引用
收藏
页数:10
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