A Theranostic Cellulose Nanocrystal-Based Drug Delivery System with Enhanced Retention in Pulmonary Metastasis of Melanoma
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A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
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Date
2021-05-06
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Language
en
Pages
13
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Small, Volume 17, issue 18
Abstract
Metastatic melanoma can be difficult to detect until at the advanced state that decreases the survival rate of patients. Several FDA-approved BRAF inhibitors have been used for treatment of metastatic melanoma, but overall therapeutic efficacy has been limited. Lutetium-177 (177Lu) enables simultaneous tracking of tracer accumulation with single-photon emission computed tomography and radiotherapy. Therefore, the codelivery of 177Lu alongside chemotherapeutic agents using nanoparticles (NPs) might improve the therapeutic outcome in metastatic melanoma. Cellulose nanocrystals (CNC NPs) can particularly deliver payloads to lung capillaries in vivo. Herein, 177Lu-labeled CNC NPs loaded with vemurafenib ([177Lu]Lu-CNC-V NPs) is developed and the therapeutic effect in BRAF V600E mutation-harboring YUMM1.G1 murine model of lung metastatic melanoma is investigated. The [177Lu]Lu-CNC-V NPs demonstrate favorable radiolabel stability, drug release profile, cellular uptake, and cell growth inhibition in vitro. In vivo biodistribution reveals significant retention of the [177Lu]Lu-CNC-V NPs in the lung, liver, and spleen. Ultimately, the median survival time of animals is doubly increased after treatment with [177Lu]Lu-CNC-V NPs compared to control groups. The enhanced therapeutic efficacy of [177Lu]Lu-CNC-V NPs in the lung metastatic melanoma animal model provides convincing evidence for the potential of clinical translation for theranostic CNC NP-based drug delivery systems after intravenous administration.Description
Funding Information: Financial support from the Finnish Cultural Foundation (grant no. 00190375), the Academy of Finland (decision nos. 318422, 278056, 298481, 302102, and 331659), and the University of Helsinki Research Funds are gratefully acknowledged. Finnish Center for Laboratory Animal Pathology (FCLAP) at HiLIFE, University of Helsinki, is acknowledged for the tissue preparation and staining services. The authors also thank Dr. Jaakko Sarparanta for help with phospho‐MEK western blot, Ms. Karina Moslova for assistance with the elemental analysis, Ms. Alexandra Correia for assistance with cell culture, and Ms. Phetcharada Imlimthan for the assistance with the images. Publisher Copyright: © 2021 The Authors. Small published by Wiley-VCH GmbH Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
Keywords
cellulose nanocrystal, drug delivery system, Lutetium-177, metastatic melanoma, theranostic nanosystem, vemurafenib
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Citation
Imlimthan, S, Khng, Y C, Keinänen, O, Zhang, W, Airaksinen, A J, Kostiainen, M A, Zeglis, B M, Santos, H A & Sarparanta, M 2021, ' A Theranostic Cellulose Nanocrystal-Based Drug Delivery System with Enhanced Retention in Pulmonary Metastasis of Melanoma ', Small, vol. 17, no. 18, 2007705 . https://doi.org/10.1002/smll.202007705