{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T18:00:21Z","timestamp":1783447221578,"version":"3.55.0"},"reference-count":40,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"3","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI094412"],"award-info":[{"award-number":["AI094412"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI064518-14"],"award-info":[{"award-number":["AI064518-14"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001117","name":"amfAR, The Foundation for AIDS Research","doi-asserted-by":"publisher","award":["109541-61-RGRL"],"award-info":[{"award-number":["109541-61-RGRL"]}],"id":[{"id":"10.13039\/100001117","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006967","name":"Center for AIDS Research, Duke University","doi-asserted-by":"publisher","award":["2037020"],"award-info":[{"award-number":["2037020"]}],"id":[{"id":"10.13039\/100006967","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:p>\n            Targeted nanocarriers deliver HIV-1 latency-reversing agents to CD4\n            <jats:sup>+<\/jats:sup>\n            T cells in the lymph nodes.\n          <\/jats:p>","DOI":"10.1126\/sciadv.aav6322","type":"journal-article","created":{"date-parts":[[2019,3,27]],"date-time":"2019-03-27T23:14:34Z","timestamp":1553728474000},"source":"Crossref","is-referenced-by-count":38,"title":["Hybrid nanocarriers incorporating mechanistically distinct drugs for lymphatic CD4\n            <sup>+<\/sup>\n            T cell activation and HIV-1 latency reversal"],"prefix":"10.1126","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9175-0813","authenticated-orcid":true,"given":"Shijie","family":"Cao","sequence":"first","affiliation":[{"name":"Department of Bioengineering, University of Washington, Seattle, WA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0559-3138","authenticated-orcid":true,"given":"Sarah D.","family":"Slack","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of Washington, Seattle, WA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3204-211X","authenticated-orcid":true,"given":"Claire N.","family":"Levy","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Washington, Seattle, WA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9409-9405","authenticated-orcid":true,"given":"Sean M.","family":"Hughes","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Washington, Seattle, WA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghou","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of Washington, Seattle, WA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Yogodzinski","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of Washington, Seattle, WA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4567-8232","authenticated-orcid":true,"given":"Pavitra","family":"Roychoudhury","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA."},{"name":"Department of Laboratory Medicine, University of Washington, Seattle, WA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8212-3789","authenticated-orcid":true,"given":"Keith R.","family":"Jerome","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA."},{"name":"Department of Laboratory Medicine, University of Washington, Seattle, WA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2598-1621","authenticated-orcid":true,"given":"Joshua T.","family":"Schiffer","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA."},{"name":"Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA."},{"name":"Department of Medicine, University of Washington, Seattle, WA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0375-2764","authenticated-orcid":true,"given":"Florian","family":"Hladik","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Washington, Seattle, WA, USA."},{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA."},{"name":"Department of Medicine, University of Washington, Seattle, WA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9508-8804","authenticated-orcid":true,"given":"Kim A.","family":"Woodrow","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of Washington, Seattle, WA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature16933"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1318249111"},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"E2512","DOI":"10.1073\/pnas.1406554111","article-title":"Anti-HIV drug particles may overcome lymphatic drug insufficiency and associated HIV persistence","volume":"111","author":"Freeling J. P.","year":"2014","unstructured":"J. P. Freeling, R. J. Y. Ho, Anti-HIV drug particles may overcome lymphatic drug insufficiency and associated HIV persistence. Proc. Natl. Acad. Sci. U.S.A. 111, E2512\u2013E2513 (2014).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.08.010"},{"key":"e_1_3_2_6_2","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.tim.2016.01.006","article-title":"HIV-1 reservoirs during suppressive therapy","volume":"24","author":"Barton K.","year":"2016","unstructured":"K. Barton, A. Winckelmann, S. Palmer, HIV-1 reservoirs during suppressive therapy. Trends Microbiol. 24, 345\u2013355 (2016).","journal-title":"Trends Microbiol."},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm880"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiv218"},{"key":"e_1_3_2_9_2","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1016\/S0140-6736(00)02854-3","article-title":"Adverse effects of antiretroviral therapy","volume":"356","author":"Carr A.","year":"2000","unstructured":"A. Carr, D. A. Cooper, Adverse effects of antiretroviral therapy. Lancet 356, 1423\u20131430 (2000).","journal-title":"Lancet"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf6517"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1255512"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1097\/COH.0000000000000279"},{"key":"e_1_3_2_13_2","doi-asserted-by":"crossref","first-page":"ofw189","DOI":"10.1093\/ofid\/ofw189","article-title":"Ongoing clinical trials of human immunodeficiency virus latency-reversing and immunomodulatory agents","volume":"3","author":"Delagr\u00e8verie H. M.","year":"2016","unstructured":"H. M. Delagr\u00e8verie, C. Delaugerre, S. R. Lewin, S. G. Deeks, J. Z. Li, Ongoing clinical trials of human immunodeficiency virus latency-reversing and immunomodulatory agents. Open Forum Infect. Dis. 3, ofw189 (2016).","journal-title":"Open Forum Infect. Dis."},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI80142"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005063"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005066"},{"key":"e_1_3_2_17_2","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1007\/s13365-015-0413-4","article-title":"Toxicity and in vitro activity of HIV-1 latency-reversing agents in primary CNS cells","volume":"22","author":"Gray L. R.","year":"2016","unstructured":"L. R. Gray, H. On, E. Roberts, H. K. Lu, M. A. Moso, J. A. Raison, C. Papaioannou, W.-J. Cheng, A. M. Ellett, J. C. Jacobson, D. F. J. Purcell, S. L. Wesselingh, P. R. Gorry, S. R. Lewin, M. J. Churchill, Toxicity and in vitro activity of HIV-1 latency-reversing agents in primary CNS cells. J. Neurovirol. 22, 455\u2013463 (2016).","journal-title":"J. Neurovirol."},{"key":"e_1_3_2_18_2","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1007\/s12195-014-0336-9","article-title":"Quantitative evaluation and optimization of co-drugging to improve anti-HIV latency therapy","volume":"7","author":"Wong V. C.","year":"2014","unstructured":"V. C. Wong, L. E. Fong, N. M. Adams, Q. Xue, S. S. Dey, K. Miller-Jensen, Quantitative evaluation and optimization of co-drugging to improve anti-HIV latency therapy. Cell. Mol. Bioeng. 7, 320\u2013333 (2014).","journal-title":"Cell. Mol. Bioeng."},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4411"},{"key":"e_1_3_2_20_2","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1182\/blood-2008-12-192203","article-title":"Noninvasive in vivo imaging of CD4 cells in simian-human immunodeficiency virus (SHIV)\u2013infected nonhuman primates","volume":"114","author":"Di Mascio M.","year":"2009","unstructured":"M. Di Mascio, C. H. Paik, J. A. Carrasquillo, J.-S. Maeng, B.-S. Jang, I. Soo Shin, S. Srinivasula, R. Byrum, A. Neria, W. Kopp, M. Catalfamo, Y. Nishimura, K. Reimann, M. Martin, H. Clifford Lane, Noninvasive in vivo imaging of CD4 cells in simian-human immunodeficiency virus (SHIV)\u2013infected nonhuman primates. Blood 114, 328\u2013337 (2009).","journal-title":"Blood"},{"key":"e_1_3_2_21_2","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1007\/BF00184787","article-title":"Distribution of lymphocyte subsets and natural killer cellsin the human body","volume":"70","author":"Westermann J.","year":"1992","unstructured":"J. Westermann, R. Pabst, Distribution of lymphocyte subsets and natural killer cellsin the human body. Clin. Investig. 70, 539\u2013544 (1992).","journal-title":"Clin. Investig."},{"key":"e_1_3_2_22_2","article-title":"Nanotechnology approaches to eradicating HIV reservoirs","author":"Cao S.","year":"2018","unstructured":"S. Cao, K. A. Woodrow, Nanotechnology approaches to eradicating HIV reservoirs. Eur. J. Pharm. Biopharm. (2018).","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"e_1_3_2_23_2","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1089\/aid.2014.0210","article-title":"Anti-HIV drug-combination nanoparticles enhance plasma drug exposure duration as well as triple-drug combination levels in cells within lymph nodes and blood in primates","volume":"31","author":"Freeling J. P.","year":"2015","unstructured":"J. P. Freeling, J. Koehn, C. Shu, J. Sun, R. J. Y. Ho, Anti-HIV drug-combination nanoparticles enhance plasma drug exposure duration as well as triple-drug combination levels in cells within lymph nodes and blood in primates. AIDS Res. Hum. Retroviruses 31, 107\u2013114 (2015).","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"e_1_3_2_24_2","doi-asserted-by":"crossref","first-page":"2143","DOI":"10.1016\/j.nano.2018.06.005","article-title":"Core-shell nanoparticles for targeted and combination antiretroviral activity in gut-homing T cells","volume":"14","author":"Cao S.","year":"2018","unstructured":"S. Cao, Y. Jiang, H. Zhang, N. Kondza, K. A. Woodrow, Core-shell nanoparticles for targeted and combination antiretroviral activity in gut-homing T cells. Nanomedicine 14, 2143\u20132153 (2018).","journal-title":"Nanomedicine"},{"key":"e_1_3_2_25_2","doi-asserted-by":"crossref","first-page":"e18270","DOI":"10.1371\/journal.pone.0018270","article-title":"Activation of latent HIV using drug-loaded nanoparticles","volume":"6","author":"Kovochich M.","year":"2011","unstructured":"M. Kovochich, M. D. Marsden, J. A. Zack, Activation of latent HIV using drug-loaded nanoparticles. PLOS ONE 6, e18270 (2011).","journal-title":"PLOS ONE"},{"key":"e_1_3_2_26_2","doi-asserted-by":"crossref","first-page":"7723","DOI":"10.1021\/nn5002694","article-title":"Bioengineered vaults: Self-assembling protein shell\u2013lipophilic core nanoparticles for drug delivery","volume":"8","author":"Buehler D. C.","year":"2014","unstructured":"D. C. Buehler, M. D. Marsden, S. Shen, D. B. Toso, X. Wu, J. A. Loo, Z. Hong Zhou, V. A. Kickhoefer, P. A. Wender, J. A. Zack, L. H. Rome, Bioengineered vaults: Self-assembling protein shell\u2013lipophilic core nanoparticles for drug delivery. ACS Nano 8, 7723\u20137732 (2014).","journal-title":"ACS Nano"},{"key":"e_1_3_2_27_2","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1186\/s11671-015-1112-z","article-title":"PLGA-PEG nanoparticles coated with anti-CD45RO and loaded with HDAC plus protease inhibitors activate latent HIV and inhibit viral spread","volume":"10","author":"Tang X.","year":"2015","unstructured":"X. Tang, Y. Liang, X. Liu, S. Zhou, L. Liu, F. Zhang, C. Xie, S. Cai, J. Wei, Y. Zhu, W. Hou, PLGA-PEG nanoparticles coated with anti-CD45RO and loaded with HDAC plus protease inhibitors activate latent HIV and inhibit viral spread. Nanoscale Res. Lett. 10, 413 (2015).","journal-title":"Nanoscale Res. Lett."},{"key":"e_1_3_2_28_2","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.2147\/IJN.S76517","article-title":"Sustained-release nanoART formulation for the treatment of neuroAIDS","volume":"10","author":"Jayant R. D.","year":"2015","unstructured":"R. D. Jayant, V. S. Atluri, M. Agudelo, V. Sagar, A. Kaushik, M. Nair, Sustained-release nanoART formulation for the treatment of neuroAIDS. Int. J. Nanomedicine 10, 1077\u20131093 (2015).","journal-title":"Int. J. Nanomedicine"},{"key":"e_1_3_2_29_2","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.virol.2014.10.033","article-title":"Short chain fatty acids potently induce latent HIV-1 in T-cells by activating P-TEFb and multiple histone modifications","volume":"474","author":"Das B.","year":"2015","unstructured":"B. Das, C. Dobrowolski, A.-M. Shahir, Z. Feng, X. Yu, J. Sha, N. F. Bissada, A. Weinberg, J. Karn, F. Ye, Short chain fatty acids potently induce latent HIV-1 in T-cells by activating P-TEFb and multiple histone modifications. Virology 474, 65\u201381 (2015).","journal-title":"Virology"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2014.44"},{"key":"e_1_3_2_31_2","doi-asserted-by":"crossref","first-page":"230","DOI":"10.3390\/molecules13020230","article-title":"Cholesterylbutyrate solid lipid nanoparticles as a butyric acid prodrug","volume":"13","author":"Brioschi A.","year":"2008","unstructured":"A. Brioschi, G. Zara, S. Calderoni, M. Gasco, A. Mauro, Cholesterylbutyrate solid lipid nanoparticles as a butyric acid prodrug. Molecules 13, 230\u2013254 (2008).","journal-title":"Molecules"},{"key":"e_1_3_2_32_2","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/j.jsb.2006.08.015","article-title":"Effect of human serum albumin on drug metabolism: Structural evidence of esterase activity of human serum albumin","volume":"157","author":"Yang F.","year":"2007","unstructured":"F. Yang, C. Bian, L. Zhu, G. Zhao, Z. Huang, M. Huang, Effect of human serum albumin on drug metabolism: Structural evidence of esterase activity of human serum albumin. J. Struct. Biol. 157, 348\u2013355 (2007).","journal-title":"J. Struct. Biol."},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg188"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.7.1726"},{"key":"e_1_3_2_35_2","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1002\/jbm.a.36315","article-title":"Optimization and comparison of CD4-targeting lipid\u2013polymer hybrid nanoparticles using different binding ligands","volume":"106","author":"Cao S.","year":"2017","unstructured":"S. Cao, Y. Jiang, C. N. Levy, S. M. Hughes, H. Zhang, F. Hladik, K. A. Woodrow, Optimization and comparison of CD4-targeting lipid\u2013polymer hybrid nanoparticles using different binding ligands. J. Biomed. Mater. Res. A 106, 1177\u20131188 (2017).","journal-title":"J. Biomed. Mater. Res. A"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2017.08.009"},{"key":"e_1_3_2_37_2","doi-asserted-by":"crossref","first-page":"11698","DOI":"10.1073\/pnas.1302634110","article-title":"Highly potent, synthetically accessible prostratin analogs induce latent HIV expression in vitro and ex vivo","volume":"110","author":"Beans E. J.","year":"2013","unstructured":"E. J. Beans, D. Fournogerakis, C. Gauntlett, L. V. Heumann, R. Kramer, M. D. Marsden, D. Murray, T.-W. Chun, J. A. Zack, P. A. Wender, Highly potent, synthetically accessible prostratin analogs induce latent HIV expression in vitro and ex vivo. Proc. Natl. Acad. Sci. U.S.A. 110, 11698\u201311703 (2013).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"e_1_3_2_38_2","doi-asserted-by":"crossref","first-page":"173","DOI":"10.2310\/7750.2012.12050","article-title":"Ingenol mebutate: A promising treatment for actinic keratoses and nonmelanoma skin cancers","volume":"17","author":"Gupta A. K.","year":"2013","unstructured":"A. K. Gupta, M. Paquet, Ingenol mebutate: A promising treatment for actinic keratoses and nonmelanoma skin cancers. J. Cutan. Med. Surg. 17, 173\u2013179 (2013).","journal-title":"J. Cutan. Med. Surg."},{"key":"e_1_3_2_39_2","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S0378-4347(00)81515-7","article-title":"Determination of free, total, and esterified cholesterol by high-performance liquid chromatography","volume":"162","author":"Duncan I. W.","year":"1979","unstructured":"I. W. Duncan, P. H. Culbreth, C. A. Burtis, Determination of free, total, and esterified cholesterol by high-performance liquid chromatography. J. Chromatogr. B Biomed. Sci. Appl. 162, 281\u2013292 (1979).","journal-title":"J. Chromatogr. B Biomed. Sci. Appl."},{"key":"e_1_3_2_40_2","doi-asserted-by":"crossref","first-page":"e0146021","DOI":"10.1371\/journal.pone.0146021","article-title":"Dose\u2013response analysis using R","volume":"10","author":"Ritz C.","year":"2015","unstructured":"C. Ritz, F. Baty, J. C. Streibig, D. Gerhard, Dose\u2013response analysis using R. PLOS ONE 10, e0146021 (2015).","journal-title":"PLOS ONE"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3489"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.aav6322","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T17:36:02Z","timestamp":1704821762000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.aav6322"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3]]},"references-count":40,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2019,3]]}},"alternative-id":["10.1126\/sciadv.aav6322"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.aav6322","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3]]},"article-number":"eaav6322"}}