Selective Trafficking of Light Chain-Conjugated Nanoparticles to the Kidney and Renal Cell Carcinoma.

Autor: Ordikhani F; Transplantation Research Center, Division of Renal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Kasinath V; Transplantation Research Center, Division of Renal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Uehara M; Transplantation Research Center, Division of Renal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Akbarzadeh A; Transplantation Research Center, Division of Renal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Yilmam OA; Transplantation Research Center, Division of Renal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Dai L; Transplantation Research Center, Division of Renal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Aksu H; Transplantation Research Center, Division of Renal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Jung S; Transplantation Research Center, Division of Renal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Jiang L; Transplantation Research Center, Division of Renal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Li X; Transplantation Research Center, Division of Renal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Zhao J; Transplantation Research Center, Division of Renal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Bahmani B; Transplantation Research Center, Division of Renal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Ichimura T; Transplantation Research Center, Division of Renal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Fiorina P; Transplantation Research Center, Division of Renal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Division of Nephrology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA., Annabi N; Chemical and Biomolecular Engineering Department and Center for Minimally Invasive Therapeutics (C-MIT), California NanoSystems Institute (CNSI), University of California - Los Angeles, Los Angeles, CA, USA., Abdi R; Transplantation Research Center, Division of Renal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Jazyk: angličtina
Zdroj: Nano today [Nano Today] 2020 Dec; Vol. 35. Date of Electronic Publication: 2020 Nov 02.
DOI: 10.1016/j.nantod.2020.100990
Abstrakt: Specific delivery platforms for drugs to the kidney and diagnostic agents to renal cell carcinoma (RCC) constitute urgent but unfulfilled clinical needs. To address these challenges, we engineered nanocarriers that interact selectively for the first time with proximal tubule epithelial cells (PTECs) in the kidney and with RCC through the interplay between lambda light chains (LCs) attached to PEGylated polylactic-co-glycolic acid (PLGA) nanoparticles and the membrane protein megalin. Systemic administration of these light chain-conjugated nanoparticles (LC-NPs) to mice resulted in their specific retention by megalin-expressing PTECs for seven days. Repetitive dosing of LC-NPs demonstrated no renal toxicity. LC-NPs also localized selectively to megalin-expressing RCC tumors in mice. Moreover, we confirmed that both the primary tumor and lymph node metastases of human RCC express megalin, reinforcing the potential of LC-NPs for clinical use. Thus, LC-NPs can contribute potentially to improving the management of both non-oncologic and oncologic renal disorders.
Competing Interests: Conflict of Interest All authors declare no conflict of interests.
Databáze: MEDLINE
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