{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T19:00:15Z","timestamp":1792522815546,"version":"4.5.0"},"reference-count":71,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"8","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2023,2,24]]},"abstract":"<jats:p>Dysfunction of collecting lymphatic vessel pumping is associated with an array of pathologies. S-(\u2212)-Bay K8644 (BayK), a small-molecule agonist of L-type calcium channels, improves vessel contractility ex vivo but has been left unexplored in vivo because of poor lymphatic access and risk of deleterious off-target effects. When formulated within lymph-draining nanoparticles (NPs), BayK acutely improved lymphatic vessel function, effects not seen from treatment with BayK in its free form. By preventing rapid drug access to the circulation, NP formulation also reduced BayK\u2019s dose-limiting side effects. When applied to a mouse model of lymphedema, treatment with BayK formulated in lymph-draining NPs, but not free BayK, improved pumping pressure generated by intact lymphatic vessels and tissue remodeling associated with the pathology. This work reveals the utility of a lymph-targeting NP platform to pharmacologically enhance lymphatic pumping in vivo and highlights a promising approach to treating lymphatic dysfunction.<\/jats:p>","DOI":"10.1126\/sciadv.abq0435","type":"journal-article","created":{"date-parts":[[2023,2,24]],"date-time":"2023-02-24T18:59:12Z","timestamp":1677265152000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":22,"title":["Lymphatic-draining nanoparticles deliver Bay K8644 payload to lymphatic vessels and enhance their pumping function"],"prefix":"10.1126","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0237-2815","authenticated-orcid":true,"given":"Lauren F.","family":"Sestito","sequence":"first","affiliation":[{"name":"Wallace H.\u00a0Coulter School of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA."},{"name":"Department of Mechanical Engineering and Bioengineering, Valparaiso University, 1900 Chapel Dr, Valparaiso, IN 46383, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim H.\u00a0T.","family":"To","sequence":"additional","affiliation":[{"name":"George W.\u00a0Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7691-3998","authenticated-orcid":true,"given":"Matthew T.","family":"Cribb","sequence":"additional","affiliation":[{"name":"George W.\u00a0Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA."},{"name":"Parker H.\u00a0Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA 30332, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1298-3887","authenticated-orcid":true,"given":"Paul A.","family":"Archer","sequence":"additional","affiliation":[{"name":"Parker H.\u00a0Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA 30332, USA."},{"name":"Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4651-232X","authenticated-orcid":true,"given":"Susan N.","family":"Thomas","sequence":"additional","affiliation":[{"name":"Wallace H.\u00a0Coulter School of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA."},{"name":"George W.\u00a0Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA."},{"name":"Parker H.\u00a0Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA 30332, USA."},{"name":"Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0351-4587","authenticated-orcid":true,"given":"J. Brandon","family":"Dixon","sequence":"additional","affiliation":[{"name":"Wallace H.\u00a0Coulter School of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA."},{"name":"George W.\u00a0Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA."},{"name":"Parker H.\u00a0Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA 30332, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_3_2_2","first-page":"H1860","article-title":"Effects of skeletal muscle fiber deformation on lymphatic volumes","volume":"259","author":"Mazzoni M. C.","year":"1990","unstructured":"M. C.\u00a0Mazzoni, T. C.\u00a0Skalak, G. W.\u00a0Schmid-Sch\u00f6nbein, Effects of skeletal muscle fiber deformation on lymphatic volumes. Am.\u00a0J.\u00a0Physiol. 259, H1860\u2013H1868 (1990).","journal-title":"Am.\u00a0J.\u00a0Physiol."},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0026-2862(84)90032-3"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2008.02.007"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.306544"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2015.00182"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI63685"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep27862"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1177\/000331979004101202"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0094713"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0070703"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvv117"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1177\/000331979504600408"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0030254"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.21037\/gs.2020.03.20"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1081\/CNV-48707"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1089\/lrb.2013.0021"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18010171"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2017.09.011"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.00137"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2002.tb04867.x"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2007.130401"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008380"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aal3920"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2014.276683"},{"key":"e_1_3_3_26_2","first-page":"1","article-title":"T-type, but not L-type, voltage-gated calcium channels are dispensable for lymphatic pacemaking and spontaneous contractions","volume":"10","author":"K.\u00a0H.\u00a0T. To","year":"2020","unstructured":"K.\u00a0H.\u00a0T. To, P.\u00a0Gui, M.\u00a0Li, S. D.\u00a0Zawieja, J. A.\u00a0Castorena-Gonzalez, M. J.\u00a0Davis, T-type, but not L-type, voltage-gated calcium channels are dispensable for lymphatic pacemaking and spontaneous contractions. Sci. Rep. 10, 1\u201324 (2020).","journal-title":"Sci. Rep."},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.2000.279.5.C1327"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00499.2017"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1997.001bi.x"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2015.12.027"},{"key":"e_1_3_3_31_2","first-page":"1463","volume-title":"J. Biomed. Mater. Res. Part A","volume":"106","author":"Schudel A.","year":"2018","unstructured":"A.\u00a0Schudel, L. F.\u00a0Sestito, S. N.\u00a0Thomas, Winner of the society for biomaterials young investigator award for the annual meeting of the society for biomaterials, April 11-14, 2018, Atlanta, GA: S-nitrosated poly(propylene sulfide) nanoparticles for enhanced nitric oxide delivery to lymphatic tissues. J. Biomed. Mater. Res. Part A 106, 1463\u20131475 (2018)."},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI27167"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00486.2004"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/wmts.102"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00692903"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2013.10.003"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsbiomaterials.6b00438"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4608"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.7b06024"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41565-020-0679-4"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-46797-2"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2022-005079"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00003.2017"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.1998.tb00614.x"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/0361-9230(88)90019-6"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2013.00243"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00039.2011"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22094455"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1089\/lrb.2014.0021"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.15238"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.090733"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2016.04.006"},{"key":"e_1_3_3_53_2","first-page":"54","article-title":"Mouse tail models of secondary lymphedema: Fibrosis gradually worsens and is irreversible","volume":"13","author":"Zhou C.","year":"2020","unstructured":"C.\u00a0Zhou, W.\u00a0Su, H.\u00a0Han, N.\u00a0Li, G.\u00a0Ma, L.\u00a0Cui, Mouse tail models of secondary lymphedema: Fibrosis gradually worsens and is irreversible. Int.\u00a0J.\u00a0Clin. Exp. Pathol. 13, 54\u201364 (2020).","journal-title":"Int.\u00a0J.\u00a0Clin. Exp. Pathol."},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsptsci.9b00047"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/293294a0"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2004.10.009"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1112648109"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2017.04.024"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2020.120411"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-2454"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1089\/153968503321642642"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mvr.2006.05.009"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI15830"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04418-y"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00598.2014"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1021\/la0478043"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01097.2011"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10439-014-1024-6"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00342.2014"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1080\/10739680490476033"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1117\/1.JBO.17.6.066019"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2013.00215"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.abq0435","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T21:41:53Z","timestamp":1704836513000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.abq0435"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,24]]},"references-count":71,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2023,2,24]]}},"alternative-id":["10.1126\/sciadv.abq0435"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.abq0435","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,24]]},"assertion":[{"value":"2022-03-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-02-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eabq0435"}}