{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T17:19:05Z","timestamp":1774027145106,"version":"3.50.1"},"reference-count":33,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,1,4]],"date-time":"2020-01-04T00:00:00Z","timestamp":1578096000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/EQU-EPR\/119631\/2010"],"award-info":[{"award-number":["PTDC\/EQU-EPR\/119631\/2010"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["FCT\/MEC (UID\/QUI\/50006\/2019)"],"award-info":[{"award-number":["FCT\/MEC (UID\/QUI\/50006\/2019)"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["RECI\/BBB-BQB\/0230\/2012"],"award-info":[{"award-number":["RECI\/BBB-BQB\/0230\/2012"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"ERDF","doi-asserted-by":"publisher","award":["PT2020 Partnership Agreement (POCI-01-0145-FEDER - 007265)"],"award-info":[{"award-number":["PT2020 Partnership Agreement (POCI-01-0145-FEDER - 007265)"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Polymers"],"abstract":"<jats:p>Doxorubicin-loaded PLGA nanoparticles conjugated with a new galactose-based ligand for the specific recognition by human hepatoma cellular carcinoma cells (Hep G2) were successfully produced. The new targeting compound was selected using molecular docking combined with quantum chemical calculations for modelling and comparing molecular interactions among the H1 subunit of the asialoglycoprotein receptor containing the carbohydrate recognition domain and the ligand. The ligand, bis(1-O-ethyl-\u03b2-D-galactopyranosyl)amine, was synthetized, characterized, and subsequently linked to PLGA. Unloaded (PLGA-di-GAL NP) and doxorubicin-loaded (DOX-PLGA-di-GAL NP) nanoparticles were prepared using an emulsion method and characterized. The produced DOX-PLGA-di-GAL NP are spherical in shape with a size of 258 \u00b1 47 nm, a zeta potential of \u221262.3 mV, and a drug encapsulation efficiency of 83%. The in vitro drug release results obtained show a three-phase release profile. In vitro cell studies confirmed the interaction between Hep G2 cells and PLGA-di-GAL NP. Cell cytotoxicity tests showed that unloaded NP are nontoxic and that DOX-PLGA-di-GAL NP caused a decrease of around 80% in cellular viability. The strategy used in this work to design new targeting compounds represents a promising tool to develop effective hepatocyte targeting drug delivery systems and can be applied to other tissues\/organs.<\/jats:p>","DOI":"10.3390\/polym12010094","type":"journal-article","created":{"date-parts":[[2020,1,6]],"date-time":"2020-01-06T03:48:48Z","timestamp":1578282528000},"page":"94","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Development of Novel Galactosylated PLGA Nanoparticles for Hepatocyte Targeting Using Molecular Modelling"],"prefix":"10.3390","volume":"12","author":[{"given":"Cl\u00e1udia D.","family":"Raposo","sequence":"first","affiliation":[{"name":"LAQV-REQUIMTE, Departamento de Qu\u00edmica, Faculdade de Ci\u00eancias e Tecnologia, Universidade NOVA de Lisboa, Quinta da Torre, 2829-516 Caparica, Portugal"}]},{"given":"Rita","family":"Costa","sequence":"additional","affiliation":[{"name":"IBET, Instituto de Biologia Experimental e Tecnol\u00f3gica, Apartado 12, 2781-901 Oeiras, Portugal"},{"name":"Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier, Universidade Nova de Lisboa, Av. da Rep\u00fablica, 2780-157 Oeiras, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2804-9880","authenticated-orcid":false,"given":"Krasimira T.","family":"Petrova","sequence":"additional","affiliation":[{"name":"LAQV-REQUIMTE, Departamento de Qu\u00edmica, Faculdade de Ci\u00eancias e Tecnologia, Universidade NOVA de Lisboa, Quinta da Torre, 2829-516 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8926-279X","authenticated-orcid":false,"given":"Catarina","family":"Brito","sequence":"additional","affiliation":[{"name":"IBET, Instituto de Biologia Experimental e Tecnol\u00f3gica, Apartado 12, 2781-901 Oeiras, Portugal"},{"name":"Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier, Universidade Nova de Lisboa, Av. da Rep\u00fablica, 2780-157 Oeiras, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4863-8057","authenticated-orcid":false,"given":"Marcus T.","family":"Scotti","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica, Centro de Ci\u00eancias Exatas e da Natureza, Universidade Federal da Para\u00edba Campus I, Jo\u00e3o Pessoa-PB 58051-900, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7766-7557","authenticated-orcid":false,"given":"M. Margarida","family":"Cardoso","sequence":"additional","affiliation":[{"name":"LAQV-REQUIMTE, Departamento de Qu\u00edmica, Faculdade de Ci\u00eancias e Tecnologia, Universidade NOVA de Lisboa, Quinta da Torre, 2829-516 Caparica, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/S0928-0987(02)00251-8","article-title":"Nanosizing: A formulation approach for poorly-water-soluble compounds","volume":"18","author":"Liversidge","year":"2003","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1016\/S1359-6446(03)02903-9","article-title":"Nanotech approaches to drug delivery and imaging","volume":"24","author":"Sahoo","year":"2003","journal-title":"Drug Discov. Today"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/S1748-0132(07)70083-X","article-title":"Targeted nanoparticles for cancer therapy","volume":"2","author":"Gu","year":"2007","journal-title":"Nano Today"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Swainson, S.M.E., Styliari, I.D., Taresco, V., and Garnett, M.C. (2019). Poly(glycerol adipate) (PGA), an enzymatically synthesized functionalizable polyester and versatile drug delivery carrier: A literature update. Polymers, 11.","DOI":"10.3390\/polym11101561"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1002\/jat.1310","article-title":"Beneficial drugs for liver diseases","volume":"28","author":"Muriel","year":"2008","journal-title":"J. Appl. Toxicol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5","DOI":"10.3322\/caac.21254","article-title":"Cancer statistics","volume":"65","author":"Siegel","year":"2015","journal-title":"CA Cancer J. Clin."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1006\/jmbi.2000.3853","article-title":"Crystal structure of the carbohydrate recognition domain of the H1 subunit of the asialoglycoprotein receptor","volume":"300","author":"Meier","year":"2000","journal-title":"J. Mol. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/S0169-409X(97)00082-3","article-title":"Receptor-mediated delivery of foreign genes to hepatocytes","volume":"29","author":"Wu","year":"1998","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1039\/c3bm60099h","article-title":"Enhanced drug delivery to hepatocellular carcinoma with a galactosylated core\u2013shell polyphosphoester nanogel","volume":"1","author":"Wu","year":"2013","journal-title":"Biomater. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1080\/10611860801902351","article-title":"Novel galactosylated SLN for hepatocyte-selective targeting of floxuridinyl diacetate","volume":"16","author":"Lian","year":"2008","journal-title":"J. Drug Target."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5216","DOI":"10.1016\/j.bmc.2008.03.017","article-title":"Trivalent, Gal\/GalNAc-containing ligands designed for the asialoglycoprotein receptor","volume":"16","author":"Khorev","year":"2008","journal-title":"Bioorg. Med. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"257","DOI":"10.3109\/1061186X.2012.741135","article-title":"In vitro and in vivo studies of galactose-modified liver-targeting liposomes","volume":"21","author":"Guo","year":"2012","journal-title":"J. Drug Target."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1080\/02652048.2016.1185474","article-title":"Doxorubicin-loaded galactose-conjugated poly(d,l-lactide-co-glycolide) nanoparticles as hepatocyte-targeting drug carrier","volume":"33","author":"Cardoso","year":"2016","journal-title":"J. Microencapsul."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Uchegbu, I.F., and Sch\u00e4tzlein, A.G. (2006). Selecting the right polymer for biomaterial applications. Polymers in Drug Delivery, CRC\/Taylor & Francis.","DOI":"10.1201\/9781420021677"},{"key":"ref_15","unstructured":"Arcamone, F. (1981). Doxorubicin: Anticancer Antibiotics, Academic Press."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/S0223-5234(01)01244-2","article-title":"Recent developments in the field of antitumour anthracyclines","volume":"36","author":"Monneret","year":"2001","journal-title":"Eur. J. Med. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/0092-8674(80)90371-2","article-title":"Galactose and N-acetylgalactosamine-specific endocytosis of glycopeptides by isolated rat hepatocytes","volume":"22","author":"Baenziger","year":"1980","journal-title":"Cell"},{"key":"ref_19","unstructured":"Perrin, D.D., and Armarego, W.L.F. (1988). Purification of Laboratory Chemicals, Butterworth-Heinemann."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3675","DOI":"10.1021\/ol048771l","article-title":"Highly efficient stereoconservative amidation and deamidation of \u03b1-amino acids","volume":"6","author":"Shendage","year":"2004","journal-title":"Org. Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"19502","DOI":"10.1074\/jbc.273.31.19502","article-title":"Mechanism of N-acetylgalactosamine binding to a C-type animal lectin carbohydrate-recognition domain","volume":"273","author":"Kolatkar","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3135","DOI":"10.1016\/S0960-894X(97)10172-X","article-title":"Synthesis of oligo(5-aminopentanoic acid)-nucleobases (APN): Potential antisense agents","volume":"7","author":"Bergmeier","year":"1997","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2025","DOI":"10.1139\/v61-272","article-title":"Some factors affecting the K\u00f6nigs-Knorr synthesis of glycosides","volume":"39","author":"Goldschmid","year":"1961","journal-title":"Can. J. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1016\/j.carres.2010.01.023","article-title":"Selective formation of glycosidic linkages of N-unsubstituted 4-hydroxyquinolin-2-(1H)-ones","volume":"345","author":"Kimmel","year":"2010","journal-title":"Carbohyd. Res."},{"key":"ref_25","unstructured":"Stick, R.V., and Williams, S.J. (2009). Carbohydrates: The Essential Molecules of Life, Elsevier."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/j.reactfunctpolym.2012.06.019","article-title":"Preparation and characterization of polymeric nanoparticles composed of poly(dl-lactide-co-glycolide) and poly(dl-lactide-co-glycolide)-co-poly(ethylene glycol)-10%-Triblock end-capped with a galactose moiety","volume":"72","author":"Peca","year":"2012","journal-title":"React. Funct. Polym."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.1182\/blood.V97.8.2221","article-title":"Systemic circulation of poly(l-lysine)\/DNA vectors is influenced by polycation molecular weight and type of DNA: Differential circulation in mice and rats and the implications for human gene delivery","volume":"97","author":"Ward","year":"2001","journal-title":"Blood"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/S0021-9258(17)43647-7","article-title":"Dependence of gluconeogenesis, urea synthesis and energy metabolism of hepatocytes on intracellular pH","volume":"259","author":"Kashiwagura","year":"1984","journal-title":"J. Biol. Chem."},{"key":"ref_29","first-page":"386","article-title":"Intracellular pH during \u201cchemical hypoxia\u201d in cultured rat hepatocytes","volume":"83","author":"Gores","year":"1989","journal-title":"Protection by intracellular acidosis against the onset of cell death. J. Clin. Invest."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1002\/hep.510260419","article-title":"Flow cytometric analysis of vesicular pH in rat hepatocytes after ethanol administration","volume":"26","author":"Kharbanda","year":"1997","journal-title":"Hepatology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1021\/js960307p","article-title":"Application of binary polymer system in drug release rate modulation. 2. Influence of formulation variables and hydrodynamic conditions on release kinetics","volume":"83","author":"Kim","year":"1997","journal-title":"J. Pharm. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/0378-5173(91)90071-U","article-title":"Mathematical modelling of drug release from hydroxypropylmethylcellulose matrices: Effect of temperature","volume":"71","author":"Ford","year":"1997","journal-title":"Int. J. Pharm."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/0168-3659(87)90035-6","article-title":"A simple equation for description of solute release II","volume":"5","author":"Ritger","year":"1987","journal-title":"Fickian and anomalous release from swellable devices. J. Control. Release"}],"container-title":["Polymers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4360\/12\/1\/94\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:18:51Z","timestamp":1760361531000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4360\/12\/1\/94"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,4]]},"references-count":33,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,1]]}},"alternative-id":["polym12010094"],"URL":"https:\/\/doi.org\/10.3390\/polym12010094","relation":{},"ISSN":["2073-4360"],"issn-type":[{"value":"2073-4360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,4]]}}}