{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T03:21:01Z","timestamp":1790479261452,"version":"4.1.0"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2014,4,1]],"date-time":"2014-04-01T00:00:00Z","timestamp":1396310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>We aim to quantify the effect of size and degree of folate loading of folate-decorated polymeric nanoparticles (NPs) on the kinetics of cellular uptake and the selection of endocytic pathways in retinal pigment epithelium (RPE) cells.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>In this study, methoxy-poly(ethylene glycol)-b-polycaprolactone (mPEG-b-PCL) and folate-functionalized PEG-b-PCL were synthesized for assembling into nanoparticles with sizes ranging from 50 nm to 250 nm. These nanoparticles were internalized into ARPE-19 (human RPE cell line) via receptor-mediated endocytosis. A two-step endocytosis process mathematical model was adopted to quantify binding affinity and uptake kinetics of nanoparticles in RPE cells in uptake and inhibition studies.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Key findings<\/jats:title>\n                  <jats:p>Nanoparticles with 100% folate loading have highest binding affinity and uptake rate in RPE cells. Maximum uptake rate (Vmax) of nanoparticles increased as the size of particles decreased from 250 nm to 50 nm. Endocytic pathway study was studied by using chlorpromazine and methyl-\u03b2-cyclodextran (M\u03b2CD), which are clathrin- and caveolae-mediated endocytosis inhibitors, respectively. Both chlorpromazine and M\u03b2CD inhibited the uptake of folate-decorated nanoparticles. Inhibition constant (Ki) and maximum uptake rate (Vmax) revealed that 50 nm and 120 nm folate-decorated nanoparticles were found to be internalized via both clathrin- and caveolae-mediated endocytosis. The 250 nm folate-decorated nanoparticles, however, were only internalized via caveolae-mediated pathway.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Increased uptake rate of folate-decorated NPs into RPE cells is observed with increasing degree of folate modification. These NPs utilize both clathrin- and caveolae-mediated receptor-mediated endocytosis pathways to enter RPE cells upon size variation. The 50 nm NPs are internalized the fastest, with clathrin-mediated endocytosis as the preferred route. Uptake of 250 nm particles is the slowest and is dominated by caveolae-mediated endocytosis.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1111\/jphp.12134","type":"journal-article","created":{"date-parts":[[2013,8,26]],"date-time":"2013-08-26T04:26:02Z","timestamp":1377491162000},"page":"564-573","source":"Crossref","is-referenced-by-count":141,"title":["Size-dependent internalisation of folate-decorated nanoparticles via the pathways of clathrin and caveolae-mediated endocytosis in ARPE-19 cells"],"prefix":"10.1093","volume":"66","author":[{"given":"Wai-Leung Langston","family":"Suen","sequence":"first","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering, The Hong Kong University of Science and Technology , Hong Kong,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Chau","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering, The Hong Kong University of Science and Technology , Hong Kong,","place":["China"]},{"name":"Division of Biomedical Engineering, The Hong Kong University of Science and Technology , Hong Kong,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,4,1]]},"reference":[{"key":"2024103109160990600_jphp12134-cit-0001","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1152\/physrev.00021.2004","article-title":"The retinal pigment epithelium in visual function","volume":"85","author":"Strauss","year":"2005","journal-title":"Physiol Rev"},{"key":"2024103109160990600_jphp12134-cit-0002","first-page":"353","article-title":"Age-related macular degeneration (AMD): pathogenesis and therapy","volume":"58","author":"Nowak","year":"2006","journal-title":"Pharmacol Rep"},{"key":"2024103109160990600_jphp12134-cit-0003","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.jconrel.2013.01.004","article-title":"Specific uptake of folate-decorated triamcinolone-encapsulating nanoparticles by retinal pigment epithelium cells enhances and prolongs antiangiogenic activity","volume":"167","author":"Suen","year":"2013","journal-title":"J Control Release"},{"key":"2024103109160990600_jphp12134-cit-0004","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/nature01451","article-title":"Regulated portals of entry into the cell","volume":"422","author":"Conner","year":"2003","journal-title":"Nature"},{"issue":"Pt 1","key":"2024103109160990600_jphp12134-cit-0005","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1042\/bj20031253","article-title":"Size-dependent internalization of particles via the pathways of clathrin- and caveolae-mediated endocytosis","volume":"377","author":"Rejman","year":"2004","journal-title":"Biochem J"},{"key":"2024103109160990600_jphp12134-cit-0006","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1152\/physrev.1997.77.3.759","article-title":"Endocytosis","volume":"77","author":"Mukherjee","year":"1997","journal-title":"Physiol Rev"},{"key":"2024103109160990600_jphp12134-cit-0007","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/nrm2122","article-title":"The multiple faces of caveolae","volume":"8","author":"Parton","year":"2007","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2024103109160990600_jphp12134-cit-0008","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1016\/j.addr.2007.06.008","article-title":"Endocytic mechanisms for targeted drug delivery","volume":"59","author":"Bareford","year":"2007","journal-title":"Adv Drug Deliv Rev"},{"key":"2024103109160990600_jphp12134-cit-0009","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1023\/A:1017991925821","article-title":"A comparison of caveolae and caveolin-1 to folate receptor alpha in retina and retinal pigment epithelium","volume":"33","author":"Bridges","year":"2001","journal-title":"Histochem J"},{"key":"2024103109160990600_jphp12134-cit-0010","volume-title":"Receptors: Models for Binding, Trafficking, and Signaling","author":"Lauffenburger","year":"1992"},{"key":"2024103109160990600_jphp12134-cit-0011","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1039\/c0py00339e","article-title":"A facile synthesis of branched poly(ethylene glycol) and its heterobifunctional derivatives","volume":"2","author":"Li Zhongyu","year":"2011","journal-title":"Polymer Chem"},{"key":"2024103109160990600_jphp12134-cit-0012","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.1002\/marc.200500591","article-title":"Schubert, PEO-b-PCL Block Copolymers: Synthesis, Detailed Characterization, and Selected Micellar Drug Encapsulation Behavior","volume":"26","author":"R. 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