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
This research paper describes a new therapeutic candidate based on a nanoparticle that co-delivers siRNA against human epidermal growth factor receptor type 2 (HER2), trastuzumab, and docetaxel to treat advanced HER2+ breast cancer. The nanotherapeutic is more effective and safer than the free drug counterparts. It inhibits drug-resistant orthotopic and brain-metastatic HER2+ breast tumors in mice. AbstractThe 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 h 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 is 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 inhibits tumor growth more effectively than the docetaxel and trastuzumab combination. When coupled with microbubble-assisted focused ultrasound that transiently disrupts the blood brain barrier, the nanoconstruct inhibits the growth ...
Source: Small - Category: Nanotechnology Authors: Worapol Ngamcherdtrakul,
Daniel S. Bejan,
William Cruz ‐Muñoz,
Moataz Reda,
Husam Y. Zaidan,
Natnaree Siriwon,
Suphalak Marshall,
Ruijie Wang,
Molly A. Nelson,
Justin P. C. Rehwaldt,
Joe W. Gray,
Kullervo Hynynen,
Wassana Yantasee Tags: Research Article Source Type: research
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