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: Tags: Research Article Source Type: research