{"doi":"10.1021/acsami.5c00816","title":"Scalable Fabrication of High-Payload Dendrimer-Based Nanoparticles for Targeted Atherosclerosis Therapy","abstract":"Nanoparticle-based therapeutics hold promise for the treatment of atherosclerosis, but challenges such as low drug-loading capacity and a lack of scalable, controllable production hinder their clinical translation. Flash nanoprecipitation, a continuous synthesis method, offers a potential solution for scalable and reproducible nanoparticle production. In this study, we employed a custom-designed multi-inlet vortex mixer to perform cross-linking reaction-enabled flash nanoprecipitation, facilitating controlled and scalable synthesis of cross-linked polyamidoamine (PAMAM) dendrimer nanoparticles. Notably, this approach allows simultaneous nanoparticle cross-linking and drug loading in a single step. The mannose moiety enabled specific targeting of macrophages via mannose receptors, enhancing the localization of the nanoparticles to atherosclerotic plaques. Atorvastatin calcium, a widely used clinical drug for atherosclerosis treatment, was selected as the model drug. This approach achieved both high production rates and high drug-loading capacities, with an output flow rate of 9.6 L/h and a nanoparticle concentration of approximately 0.4 g/L. The optimized formulation exhibited a drug-loading capacity of 37% and an encapsulation efficiency of 76%. In vitro and in vivo experiments demonstrated effective macrophage and plaque targeting, leading to significant therapeutic benefits. Treatment with these nanoparticles resulted in approximately 40% inhibition of aortic root plaque progression compared to the free drug-treated group. This scalable and efficient nanoparticle platform is a promising strategy for improving atherosclerosis treatment.","journal":"ACS Applied Materials & Interfaces","year":2025,"id":516605,"datarank":0.3596842909197557,"base_score":2.3978952727983707,"endowment":2.3978952727983707,"self_citation_contribution":0.3596842909197557,"citation_network_contribution":0.0,"self_endowment_contribution":0.3596842909197557,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9457,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":84962,"name":"Lin Qi","orcid":null,"position":1,"is_corresponding":false},{"id":647605,"name":"Da Huang","orcid":"0000-0003-3621-5233","position":2,"is_corresponding":false},{"id":967429,"name":"Jiandong Wu","orcid":"0000-0002-6672-5114","position":3,"is_corresponding":false},{"id":512974,"name":"Honglan Shi","orcid":"0000-0002-0801-5683","position":4,"is_corresponding":false},{"id":274539,"name":"Hu Yang","orcid":"0000-0003-3030-004X","position":5,"is_corresponding":false},{"id":766473,"name":"Huari Kou","orcid":null,"position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:48:49.486328Z","pmid":"40237537","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":[]}