Subcutaneous delivery of nanoconjugated doxorubicin and cisplatin for locally advanced breast cancer demonstrates improved efficacy and decreased toxicity at lower doses than standard systemic combination therapy in vivo.
Subcutaneous delivery of nanoconjugated doxorubicin and cisplatin for locally advanced breast cancer demonstrates improved efficacy and decreased toxicity at lower doses than standard systemic combination therapy in vivo.
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DOI：
10.1016/j.amjsurg.2011.06.027
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发表时间：
2011-12
影响因子：
3
通讯作者：
Cohen, Mark S.
中科院分区：
文献类型：
--
作者：
Cohen, Stephanie M.;Mukerji, Ridhwi;Cai, Shuang;Damjanov, Ivan;Forrest, M. Laird;Cohen, Mark S.
关键词：
乳腺癌联合细胞毒性药物具有剂量限制性毒性。我们假设纳米载体结合的多柔比星和顺铂与标准药物相比，即使在较低剂量下，也具有改善的肿瘤疗效和降低的全身毒性。在雌性Nu/Nu小鼠的乳房中注射人MDA-MB-468 LN细胞，并以50%或75%MTD用标准或纳米载体缀合的组合疗法（多柔比星+顺铂）治疗，并在12周内监测功效和毒性。用50%MTD的HA缀合的多柔比星/顺铂治疗的小鼠的功效结果包括：[完全响应（CR）=5，部分响应（PR）=2，并且疾病稳定（SD）=1]，并且对于75%MTD的HA缀合的dox/cis：[CR=7，PR=1;所有CR均经组织学证实]。相比之下，给予标准dox/cis（50%MTD）的小鼠显示：[进行性疾病（PD）=6，SD=1，和PR=1]，并且对于标准dox/cis（75%MTD）：[PD=5，SD=3;在多变量ANOVA上p<0.0001]。在75%MTD下，与纳米载体药物治疗的小鼠相比，标准药物治疗的小鼠具有显著的体重减轻（p<0.001）。与标准药剂组合疗法相比，多柔比星和顺铂的皮下纳米载体递送在所有测试剂量下均显示出显著改善的功效和降低的毒性，从而实现完全病理肿瘤反应。
Combination cytotoxic agents in breast cancer carry dose-limiting toxicities. We hypothesize that nanocarrier-conjugated doxorubicin and cisplatin will have improved tumor efficacy with decreased systemic toxicity over standard drugs, even at lower doses. Female Nu/Nu mice were injected in the breast with human MDA-MB-468LN cells and treated with either standard or nanocarrier-conjugated combination therapy (doxorubicin+cisplatin) at 50% or 75% MTD, and monitored for efficacy and toxicity over 12-weeks. Efficacy results for mice treated with HA-conjugated doxorubicin/cisplatin at 50% MTD include:[complete responses(CR)=5, partial responses(PR)=2, and stable disease(SD)=1]and for HA-conjugated dox/cis at 75% MTD:[CR=7,PR=1; all CR’s confirmed histologically]. In comparison, mice given standard dox/cis(50% MTD)demonstrated:[progressive disease(PD)=6, SD=1, and PR=1] and for standard dox/cis(75% MTD):[PD=5,SD=3; p<0.0001 on multivariate ANOVA]. At 75% MTD, standard drug-treated mice had significant weight loss compared to nanocarrier drug-treated mice(p<0.001). Subcutaneous nanocarrier-delivery of doxorubicin and cisplatin demonstrated significantly improved efficacy with decreased toxicity compared to standard agent combination therapy at all doses tested achieving complete pathologic tumor response.
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影响因子：
6.6
作者：
Xie Y;Bagby TR;Cohen MS;Forrest ML
通讯作者：
Forrest ML
影响因子：
8.4
作者：
Liljegren, G;Holmberg, L
通讯作者：
Holmberg, L
影响因子：
3.9
作者：
Chen, JH;Ling, R;Li, KZ
通讯作者：
Li, KZ
影响因子：
2.2
作者：
Cai, Shuang;Xie, Yumei;Forrest, M. Laird
通讯作者：
Forrest, M. Laird
DOI：
10.1016/j.jconrel.2010.04.006
发表时间：
2010-09-01
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Cai S;Thati S;Bagby TR;Diab HM;Davies NM;Cohen MS;Forrest ML
通讯作者：
Forrest ML