MiR126-targeted-nanoparticles combined with PI3K/AKT inhibitor as a new strategy to overcome melanoma resistance.

Autor:	Arasi MB; Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy., De Luca G; Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy., Chronopoulou L; Department of Chemistry, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy; Research Center for Applied Sciences to the safeguard of Environment and Cultural Heritage (CIABC) Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy., Pedini F; Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy., Petrucci E; Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy., Flego M; National Center for Global Health, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy., Stringaro A; National Center for Drug Research and Evaluation, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy., Colone M; National Center for Drug Research and Evaluation, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy., Pasquini L; Core Facilities, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy., Spada M; Center of Animal Research and Welfare, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy., Lulli V; Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy., Perrotta MC; Department of Chemistry, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy., Calin GA; Translational Molecular Pathology, MD Anderson Cancer Center, Texas State University, 1515 Holcombe Blvd, Houston, TX 77030, USA; The RNA Interference and Non-coding RNA Center, MD Anderson Cancer Center, Texas State University, Houston, 1515 Holcombe Blvd, Houston, TX 77030, USA., Palocci C; Department of Chemistry, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy; Research Center for Applied Sciences to the safeguard of Environment and Cultural Heritage (CIABC) Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy., Biffoni M; Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy., Felicetti F; Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy., Felli N; Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. Electronic address: nadia.felli@iss.it.
Jazyk:	angličtina
Zdroj:	Molecular therapy : the journal of the American Society of Gene Therapy [Mol Ther] 2024 Jan 03; Vol. 32 (1), pp. 152-167. Date of Electronic Publication: 2023 Nov 21.
DOI:	10.1016/j.ymthe.2023.11.021
Abstrakt:	Metastatic melanoma poses significant challenges as a highly lethal disease. Despite the success of molecular targeting using BRAF V600E inhibitors (BRAFis) and immunotherapy, the emergence of early recurrence remains an issue and there is the need for novel therapeutic approaches. This study aimed at creating a targeted delivery system for the oncosuppressor microRNA 126 (miR126) and testing its effectiveness in combination with a phosphatidylinositol 3-kinase (PI3K)/ protein kinase B (AKT) inhibitor for treating metastatic melanoma resistant to BRAFis. To achieve this, we synthesized chitosan nanoparticles containing a chemically modified miR126 sequence. These nanoparticles were further functionalized with an antibody specific to the chondroitin sulfate proteoglycan 4 (CSPG4) melanoma marker. After evaluation in vitro, the efficacy of this treatment was evaluated through an in vivo experiment using mice bearing resistant human melanoma. The co-administration of miR126 and the PI3K/AKT inhibitor in these experiments significantly reduced tumor growth and inhibited the formation of liver and lung metastases. These results provide evidence for a strategy to target an oncosuppressive nucleic acid sequence to tumor cells while simultaneously protecting it from plasma degradation. The system described in this study exhibits encouraging potential for the effective treatment of therapy-resistant metastatic melanoma while also presenting a prospective approach for other forms of cancer. Competing Interests: Declaration of interests The authors declare that the data presented in this study are the subject of an industrial invention patent field on behalf of the Istituto Superiore di Sanità. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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