Sphingomyelin-Based Nanosystems (SNs) for the Development of Anticancer miRNA Therapeutics

Nagachinta, Surasa; Bouzo, Belén L.; Vázquez-Ríos, Abi Judit; López, Rafael; Fuente, María de la

doi:10.3390/pharmaceutics12020189

Cited by 31 publications

(28 citation statements)

References 50 publications

(59 reference statements)

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“…ET-NEs, and their control formulation (C-NEs) were prepared by adapting the ethanol injection method previously optimized by our group for the preparation of nanometric emulsions on a single step 37 , 38 , allowing the straightforward formation of the nanosystems, as represented in Fig. 1 .…”

Section: Resultsmentioning

confidence: 99%

Edelfosine nanoemulsions inhibit tumor growth of triple negative breast cancer in zebrafish xenograft model

Saraiva

Gutiérrez-Lovera

Martínez-Val

et al. 2021

Sci Rep

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Triple negative breast cancer (TNBC) is known for being very aggressive, heterogeneous and highly metastatic. The standard of care treatment is still chemotherapy, with adjacent toxicity and low efficacy, highlighting the need for alternative and more effective therapeutic strategies. Edelfosine, an alkyl-lysophospholipid, has proved to be a promising therapy for several cancer types, upon delivery in lipid nanoparticles. Therefore, the objective of this work was to explore the potential of edelfosine for the treatment of TNBC. Edelfosine nanoemulsions (ET-NEs) composed by edelfosine, Miglyol 812 and phosphatidylcholine as excipients, due to their good safety profile, presented an average size of about 120 nm and a neutral zeta potential, and were stable in biorelevant media. The ability of ET-NEs to interrupt tumor growth in TNBC was demonstrated both in vitro, using a highly aggressive and invasive TNBC cell line, and in vivo, using zebrafish embryos. Importantly, ET-NEs were able to penetrate through the skin barrier of MDA-MB 231 xenografted zebrafish embryos, into the yolk sac, leading to an effective decrease of highly aggressive and invasive tumoral cells’ proliferation. Altogether the results demonstrate the potential of ET-NEs for the development of new therapeutic approaches for TNBC.

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Section: Resultsmentioning

confidence: 99%

Edelfosine nanoemulsions inhibit tumor growth of triple negative breast cancer in zebrafish xenograft model

Saraiva

Gutiérrez-Lovera

Martínez-Val

et al. 2021

Sci Rep

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“…Similar to PC and other phospholipids, sphingomyelin provides high bioavailability for liposomal drug delivery systems. A sphingomyelin-based nanosystem was recently investigated for miRNA delivery ( Nagachinta et al ., 2020 ). The lipid formulations comprised vitamin E, stearylamine or N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methylsulfate (DOTAP), PEG 12 -C 18 , and sphingomyelin.…”

Section: Sphingolipidsmentioning

confidence: 99%

“…The generated sphingomyelin-based miRNA-encapsulated lipid nanoparticles showed higher cellular uptake, transfection efficiency, and anticancer effects compared to miRNA-tethered liposomes composed of stearylamine and sphingomyelin. This likely reflects that the encapsulation of miRNA inside the sphingomyelin lipid layer avoided its premature release ( Nagachinta et al ., 2020 ).…”

Section: Sphingolipidsmentioning

confidence: 99%

Bioactive Lipids and Their Derivatives in Biomedical Applications

Park

Choi

Kim

et al. 2021

Biomolecules & Therapeutics

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Lipids, which along with carbohydrates and proteins are among the most important nutrients for the living organism, have a variety of biological functions that can be applied widely in biomedicine. A fatty acid, the most fundamental biological lipid, may be classified by length of its aliphatic chain, and the short-, medium-, and long-chain fatty acids and each have distinct biological activities with therapeutic relevance. For example, short-chain fatty acids have immune regulatory activities and could be useful against autoimmune disease; medium-chain fatty acids generate ketogenic metabolites and may be used to control seizure; and some metabolites oxidized from long-chain fatty acids could be used to treat metabolic disorders. Glycerolipids play important roles in pathological environments, such as those of cancers or metabolic disorders, and thus are regarded as a potential therapeutic target. Phospholipids represent the main building unit of the plasma membrane of cells, and play key roles in cellular signaling. Due to their physical properties, glycerophospholipids are frequently used as pharmaceutical ingredients, in addition to being potential novel drug targets for treating disease. Sphingolipids, which comprise another component of the plasma membrane, have their own distinct biological functions and have been investigated in nanotechnological applications such as drug delivery systems. Saccharolipids, which are derived from bacteria, have endotoxin effects that stimulate the immune system. Chemically modified saccharolipids might be useful for cancer immunotherapy or as vaccine adjuvants. This review will address the important biological function of several key lipids and offer critical insights into their potential therapeutic applications.

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“…In a previous study, we observed that DOTAP showed a superior miRNA-complexing capacity than ST, forming stable lipoplexes. In addition, when encapsulating these DOTAP lipoplexes in nanoemulsions, the resultant nanosystems presented significantly higher internalization and transfection efficiencies than nanosystems containing ST [ 28 ].…”

Section: Introductionmentioning

confidence: 99%

Modulation of Colorectal Tumor Behavior via lncRNA TP53TG1-Lipidic Nanosystem

et al. 2021

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Long non-coding RNAs (lncRNAs) are an emerging group of RNAs with a crucial role in cancer pathogenesis. In gastrointestinal cancers, TP53 target 1 (TP53TG1) is an epigenetically regulated lncRNA that represents a promising therapeutic target due to its tumor suppressor properties regulating the p53-mediated DNA damage and the intracellular localization of the oncogenic YBX1 protein. However, to translate this finding into the clinic as a gene therapy, it is important to develop effective carriers able to deliver exogenous lncRNAs to the targeted cancer cells. Here, we propose the use of biocompatible sphingomyelin nanosystems comprising DOTAP (DSNs) to carry and deliver a plasmid vector encoding for TP53TG1 (pc(TP53TG1)-DSNs) to a colorectal cancer cell line (HCT-116). DSNs presented a high association capacity and convenient physicochemical properties. In addition, pc(TP53TG1)-DSNs showed anti-tumor activities in vitro, specifically a decrease in the proliferation rate, a diminished colony-forming capacity, and hampered migration and invasiveness of the treated cancer cells. Consequently, the proposed strategy displays a high potential as a therapeutic approach for colorectal cancer.

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Sphingomyelin-Based Nanosystems (SNs) for the Development of Anticancer miRNA Therapeutics

Cited by 31 publications

References 50 publications

Edelfosine nanoemulsions inhibit tumor growth of triple negative breast cancer in zebrafish xenograft model

Edelfosine nanoemulsions inhibit tumor growth of triple negative breast cancer in zebrafish xenograft model

Bioactive Lipids and Their Derivatives in Biomedical Applications

Modulation of Colorectal Tumor Behavior via lncRNA TP53TG1-Lipidic Nanosystem

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