{"doi":"10.1002/smll.202107550","title":"Targeted Nanoparticle for Co‐delivery of HER2 siRNA and a Taxane to Mirror the Standard Treatment of HER2<b>+</b> Breast Cancer: Efficacy in Breast Tumor and Brain Metastasis","abstract":"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 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 of trastuzumab-resistant HER2+ BT474 tumors residing in the 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.","journal":"Small","year":2022,"id":239661,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":48,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9611,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":686653,"name":"Daniel S. Bejan","orcid":"0000-0002-5090-0299","position":1,"is_corresponding":false},{"id":866672,"name":"William Cruz‐Muñoz","orcid":null,"position":2,"is_corresponding":false},{"id":816563,"name":"Moataz Reda","orcid":null,"position":3,"is_corresponding":false},{"id":816566,"name":"Husam Y. Zaidan","orcid":null,"position":4,"is_corresponding":false},{"id":816564,"name":"Natnaree Siriwon","orcid":null,"position":5,"is_corresponding":false},{"id":865871,"name":"Suphalak Khamruang Marshall","orcid":"0000-0002-0481-3688","position":6,"is_corresponding":false},{"id":816124,"name":"Ruijie Wang","orcid":"0000-0001-9611-4974","position":7,"is_corresponding":false},{"id":816125,"name":"Molly A. Nelson","orcid":"0000-0002-3775-3503","position":8,"is_corresponding":false},{"id":843403,"name":"Justin P. C. Rehwaldt","orcid":null,"position":9,"is_corresponding":false},{"id":225103,"name":"Joe W. Gray","orcid":"0000-0001-9225-6756","position":10,"is_corresponding":false},{"id":232451,"name":"Kullervo Hynynen","orcid":"0000-0001-6219-2982","position":11,"is_corresponding":false},{"id":257653,"name":"Wassana Yantasee","orcid":"0000-0002-0989-363X","position":12,"is_corresponding":false},{"id":816123,"name":"Worapol Ngamcherdtrakul","orcid":"0000-0003-4187-7709","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":null,"created_at":"2026-07-19T00:22:41.699779Z","pmid":"35083840","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}