{"doi":"10.1002/adtp.202200173","title":"Identification of an ALK‐2 Inhibitor as an Agonist for Intercellular Exchange and Tumor Delivery of Nanomaterial","abstract":"Abstract Inefficient extravasation and penetration in solid tissues hinder the clinical outcome of nanoparticles (NPs). Recent studies have shown the extravasation and penetration of NPs in solid tumor are mostly achieved via an active transcellular route. Numerous efforts are devoted to elucidate the endocytosis and subcellular trafficking of NPs. However, how they exit from one cell and re‐enter into neighboring ones (termed intercellular exchange) remains poorly understood. The previous study showed that a significant portion of NPs are transferred inside extracellular vesicles (EVs). Inhibition of EV biogenesis significantly reduces tumor accumulation and vascular penetration of various NPs in vivo. Here, a manual chemical screen is performed with this assay, which identifies that LDN‐214117 (an inhibitor for activin receptor‐like kinase‐2, ALK‐2) as an agonist of NP intercellular exchange. LDN‐214117 is showed to regulate the intercellular exchange by increasing the EV biogenesis via bone morphogenetic protein–mitogen‐activated protein kinase (BMP–MAPK) signaling pathway. LDN‐214117 treatment further enhances tumor accumulation and vascular penetration of a variety of NPs in multiple tumor models, which improves their antitumor efficacy. Overall, the identification of a novel chemical compound with intercellular exchange assay is showcase to modulate EV‐mediated transport, thus boosting the delivery and therapeutic efficacy of nanomaterials.","journal":"Advanced Therapeutics","year":2022,"id":287761,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9492,"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":816087,"name":"Hong Guo","orcid":"0000-0001-8024-7086","position":1,"is_corresponding":false},{"id":967781,"name":"Jiaqi Zhao","orcid":"0000-0002-2950-6799","position":2,"is_corresponding":false},{"id":716516,"name":"Yushuang Wei","orcid":"0009-0002-5660-1609","position":3,"is_corresponding":false},{"id":300173,"name":"Yuexuan Li","orcid":null,"position":4,"is_corresponding":false},{"id":300174,"name":"Hong‐Bo Pang","orcid":null,"position":5,"is_corresponding":false},{"id":87214,"name":"Xian Wu","orcid":"0000-0003-1118-9710","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-19T00:30:01.051685Z","pmid":"36818419","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":[]}