A1 Refereed original research article in a scientific journal
A Theranostic Cellulose Nanocrystal-Based Drug Delivery System with Enhanced Retention in Pulmonary Metastasis of Melanoma
Authors: Imlimthan Surachet, Khng You Cheng, Keinänen Outi, Zhang Wenzhong, Airaksinen Anu J., Kostiainen Mauri A., Zeglis Brian M., Santos Hélder A., Sarparanta Mirkka
Publisher: WILEY-V C H VERLAG GMBH
Publication year: 2021
Journal: Small
Journal name in source: SMALL
Journal acronym: SMALL
Article number: 2007705
Volume: 17
Issue: 18
Number of pages: 13
ISSN: 1613-6810
eISSN: 1613-6829
DOI: https://doi.org/10.1002/smll.202007705
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/53651813
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.
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