title: Albumin-based nanoparticles as methylprednisolone carriers for targeted delivery towards the neonatal Fc receptor in glomerular podocytes.
abstract: Glucocorticoids (GCs) are commonly used in the treatment of nephrotic syndrome. However, high doses and long periods of GC therapy can result in severe side effects. The present study aimed to selectively deliver albumin‑methylprednisolone (MP) nanoparticles towards glomerular podocytes, which highly express the specific neonatal Fc receptor (FcRn) of albumin. Bovine serum albumin (BSA) was labeled with a fluorescent dye and linked with modified MP via an amide bond. The outcome nanoparticle named BSA633‑MP showed a uniform size with a diameter of approximately 10 nm and contained 12 drug molecules on average. The nanoconjugates were found to be stable at pH 7.4 and acid‑sensitive at pH 4.0, with approximately 72% release of the MP drug after 48 h of incubation. The nanoparticle demonstrated a 36‑fold uptake in receptor‑specific cellular delivery in the FcRn‑expressing human podocytes compared to the uptake in the non-FcRn-expressing control cells. Co‑localization further confirmed that uptake of the nanoconjugates involved receptor‑mediated endocytosis followed by lysosome associated transportation. In vitro cellular experiments indicated that the BSA633‑MP ameliorated puromycin aminonucleoside‑induced podocyte apoptosis. Moreover, in vivo fluorescence molecular imaging showed that BSA633-MP was mainly accumulated in the liver and kidney after intravenous dosing for 24 h. Collectively, this study may provide an approach for the effective and safe therapy of nephrotic syndrome.
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Mingyu
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Mao
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Ningning
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Xiufen
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Qian
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Changying
authors.initials: C
authors.lastname: Xing
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002417:Cattle; D002461:Cell Line, Transformed; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D008775:Methylprednisolone / Q000737:chemistry / Q000494:pharmacology; D053758:Nanoparticles / Q000737:chemistry*; D050199:Podocytes / Q000378:metabolism*; D011692:Puromycin Aminonucleoside / Q000009:adverse effects / Q000494:pharmacology; D011961:Receptors, Fc / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000494:pharmacology
chemical_list: D004337:Drug Carriers; D015395:Histocompatibility Antigens Class I; D011961:Receptors, Fc; D012710:Serum Albumin, Bovine; D011692:Puromycin Aminonucleoside; C100688:Fc receptor, neonatal; D008775:Methylprednisolone