Targeted Nanoparticle for Co-delivery of HER2 siRNA and a Taxane to Mirror the Standard Treatment of HER2+ Breast Cancer: Efficacy in Breast Tumor and Brain Metastasis.
Targeted Nanoparticle for Co-delivery of HER2 siRNA and a Taxane to Mirror the Standard Treatment of HER2+ Breast Cancer: Efficacy in Breast Tumor and Brain Metastasis.
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DOI：
10.1002/smll.202107550
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Yantasee W
中科院分区：
文献类型：
--
作者：
Ngamcherdtrakul W;Bejan DS;Cruz-Muñoz W;Reda M;Zaidan HY;Siriwon N;Marshall S;Wang R;Nelson MA;Rehwaldt JPC;Gray JW;Hynynen K;Yantasee W
晚期和转移性人表皮生长因子受体2型（HER2+）乳腺癌的一线治疗需要两种HER2靶向抗体（曲妥珠单抗和帕妥珠单抗）和紫杉烷（多西他赛或紫杉醇）。三种药物方案每个疗程的费用超过320，000美元，需要4小时的输注时间，并且具有许多不良副作用，同时仅实现18个月的无进展生存期。为了替代该方案，减少输注时间并提高疗效，开发了基于曲妥珠单抗缀合的纳米颗粒的单一治疗剂，用于共同递送多西他赛和针对HER2的siRNA（siHER2）。最佳的纳米构建体具有100 nm的流体动力学尺寸，并且特异性地治疗HER2+乳腺癌细胞而不是器官来源的正常细胞。在耐药原位HER2+ HCC 1954肿瘤小鼠模型中，纳米构建体比多西他赛和曲妥珠单抗组合更有效地抑制肿瘤生长。当与瞬时破坏血脑屏障的微泡辅助聚焦超声结合时，纳米结构抑制了小鼠脑中曲妥珠单抗耐药HER2+ BT474肿瘤的生长。该纳米构建体在细胞和小鼠中具有良好的安全性。联合疗法已成为癌症治疗的基石，这种多功能纳米颗粒平台可以共同提供多种治疗类型，以确保它们同时到达靶细胞，实现其协同作用。
The first-line treatment of advanced and metastatic human epidermal growth factor receptor type 2 (HER2+) breast cancer requires two HER2-targeting antibodies (trastuzumab and pertuzumab) and a taxane (docetaxel or paclitaxel). The three-drug regimen costs over $320,000 per treatment course, requires a 4-hour infusion time, and has many adverse side effects, while achieving only 18 months of progression-free survival. To replace this regimen, reduce infusion time, and enhance efficacy, a single therapeutic was developed based on trastuzumab-conjugated nanoparticles for co-delivering docetaxel and siRNA against HER2 (siHER2). The optimal nanoconstruct has a hydrodynamic size of 100 nm and specifically treats HER2+ breast cancer cells over organ-derived normal cells. In a drug-resistant orthotopic HER2+ HCC1954 tumor mouse model, the nanoconstruct inhibited tumor growth more effectively than the docetaxel and trastuzumab combination. When coupled with microbubble-assisted focused ultrasound that transiently disrupted the blood brain barrier, the nanoconstruct inhibited the growth of trastuzumab-resistant HER2+ BT474 tumors residing in brains of mice. The nanoconstruct has a favorable safety profile in cells and in mice. Combination therapies have become the cornerstone of cancer treatment and this versatile nanoparticle platform can co-deliver multiple therapeutic types to ensure that they reach the target cells at the same time to realize their synergy.
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影响因子：
5.7
作者：
Morry J;Ngamcherdtrakul W;Gu S;Reda M;Castro DJ;Sangvanich T;Gray JW;Yantasee W
通讯作者：
Yantasee W
影响因子：
5.2
作者：
Barone M;Chain F;Sokol H;Brigidi P;Bermúdez-Humarán LG;Langella P;Martín R
通讯作者：
Martín R
影响因子：
3.7
作者：
Gu S;Ngamcherdtrakul W;Reda M;Hu Z;Gray JW;Yantasee W
通讯作者：
Yantasee W
DOI：
10.1158/1078-0432.ccr-09-0931
发表时间：
2009-10-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Francia G;Man S;Lee CJ;Lee CR;Xu P;Mossoba ME;Emmenegger U;Medin JA;Kerbel RS
通讯作者：
Kerbel RS
DOI：
10.1007/978-3-319-22536-4_16
发表时间：
2016-01-01
期刊：
THERAPEUTIC ULTRASOUND
影响因子：
--
作者：
Burgess, Alison;Hynynen, Kullervo
通讯作者：
Hynynen, Kullervo