Sphingomyelin nanosystems loaded with uroguanylin and etoposide for treating metastatic colorectal cancer

Bouzo, Belén L.; Lores, Saínza; Jatal, Raneem; Alijas, Sandra; Alonso, María José; Conejos‐Sánchez, Inmaculada; Fuente, María de la

doi:10.1038/s41598-021-96578-z

Cited by 16 publications

(11 citation statements)

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“…56,57 Previous results from our group highlight the potential of SNs for the development of new cancer therapeutics. [34][35][36][37][38] For gene therapy applications, they have already been tested for delivery of microRNA (miRNA) and pDNA upon modification with the cationic lipids DOTAP and stearylamine. 14,58 Here, we have selected putrescine, a natural polyamine presented in eukaryotic cells for which cancer cells are ravenous due to their increased metabolic activity, 26,59 as the cationic material for the development of a new type of cationic SNs 14,33,34 for cancer gene therapy applications.…”

Section: Development Of Cationic Putrescine Nanosystemsmentioning

confidence: 99%

“…In this work, we propose the incorporation of a putrescine derivative, oleamide-modified putrescine, in sphingomyelin nanosystems (SNs), previously developed by our group, 14,[33][34][35][36][37][38][39] and composed by vitamin E, a GRAS-listed excipient, 40 and sphingomyelin, one of the main components of cell membranes. 41 We aim to prove the therapeutic potential of putrescine-SNs (PSNs) that associate a plasmid encoding the apoptotic Fas Ligand (FasL) 42,43 for treating highly aggressive triple-negative breast cancer (TNBC).…”

Section: Introductionmentioning

confidence: 99%

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Effectiveness of a novel gene nanotherapy based on putrescine for cancer treatment

et al. 2023

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Section: Development Of Cationic Putrescine Nanosystemsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effectiveness of a novel gene nanotherapy based on putrescine for cancer treatment

et al. 2023

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“…CAL02, a potential infection-controlling liposome composed of cholesterol and sphingomyelin, has been discussed as a novel anti-infection strategy, indicating that the antibacterial functions of antimicrobial lipids are worth to be investigated further ( 181 ). Sphingomyelin nanosystems are the promising form of carriers with potential for the combination of various types of medications ( 182 – 184 ). Bouzo et al ( 182 ) encapsulated the anti-cancer drug etoposide in the sphingomyelin nanosystems, which mediated an antiproliferative response by interacting with colorectal cancer cells expressing the guanylyl cyclase receptor.…”

Section: Application Of Dietary Sphingomyelin In Foodmentioning

confidence: 99%

“…Sphingomyelin nanosystems are the promising form of carriers with potential for the combination of various types of medications ( 182 – 184 ). Bouzo et al ( 182 ) encapsulated the anti-cancer drug etoposide in the sphingomyelin nanosystems, which mediated an antiproliferative response by interacting with colorectal cancer cells expressing the guanylyl cyclase receptor. Nagachinta et al ( 183 ) designed sphingomyelin-based biocompatible nanosystems for intracellular delivery of microRNAs to colorectal cancer cells.…”

Section: Application Of Dietary Sphingomyelin In Foodmentioning

confidence: 99%

The nutritional functions of dietary sphingomyelin and its applications in food

Yang

Chen

2022

Front. Nutr.

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Sphingolipids are common structural components of cell membranes and are crucial for cell functions in physiological and pathophysiological conditions. Sphingomyelin and its metabolites, such as sphingoid bases, ceramide, ceramide-1-phosphate, and sphingosine-1-phosphate, play signaling roles in the regulation of human health. The diverse structures of sphingolipids elicit various functions in cellular membranes and signal transduction, which may affect cell growth, differentiation, apoptosis, and maintain biological activities. As nutrients, dietary sphingomyelin and its metabolites have wide applications in the food and pharmaceutical industry. In this review, we summarized the distribution, classifications, structures, digestion, absorption and metabolic pathways of sphingolipids, and discussed the nutritional functioning of sphingomyelin in chronic metabolic diseases. The possible implications of dietary sphingomyelin in the modern food preparations including dairy products and infant formula, skin improvement, delivery system and oil organogels are also evaluated. The production of endogenous sphingomyelin is linked to pathological changes in obesity, diabetes, and atherosclerosis. However, dietary supplementations of sphingomyelin and its metabolites have been shown to maintain cholesterol homeostasis and lipid metabolism, and to prevent or treat these diseases. This seemly paradoxical phenomenon shows that dietary sphingomyelin and its metabolites are candidates for food additives and functional food development for the prevention and treatment of chronic metabolic diseases in humans.

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“…In a clinical trial, using Etoposide improved overall survival in patients with extensivestage small-cell lung cancer (ES-SCLC) [274,275]. Etoposide was found to have the potential as a treatment for metastatic colorectal cancer when it was used as a combined therapy [276]. Mitoxantrone is an FDA-approved drug for Leukemia, and prostate cancer.…”

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confidence: 99%

Explainable artificial intelligence for patient stratification and drug repositioning

Al-Taie¹

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Enabling precision medicine requires developing robust patient stratification methods as well as drugs tailored to homogeneous subgroups of patients from a heterogeneous population. Developing de novo drugs is expensive and time consuming with an ultimately low FDA approval rate. These limitations make developing new drugs for a small portion of a disease population unfeasible. Therefore, drug repositioning is an essential alternative for developing new drugs for a disease subpopulation. There is a crucial need to develop data-driven approaches that find druggable homogeneous subgroups within the disease population and reposition the drugs for these subgroups. In this study, we developed an explainable AI approach for patient stratification and drug repositioning. Exploratory mining mimicking the trial recruitment process as well as network analysis were used to discover homogeneous subgroups within a disease population. For each subgroup, a biomedical network analysis was done to find the drugs that are most relevant to a given subgroup of patients. The set of candidate drugs for each subgroup was ranked using an aggregated drug score assigned to each drug. The method represents a human-in-the-loop framework, where medical experts use data-driven results to generate hypotheses and obtain insights into potential therapeutic candidates for patients who belong to a subgroup. To examine the validity of our method, we implemented our method on individual cancer types and on pan-cancer data to consider the inter- and intra-heterogeneity within a cancer type and among cancer types. Patients' phenotypic and genotypic data was utilized with a heterogeneous knowledge base because it gives a multi-view perspective for finding new indications for drugs outside of their original use. Our analysis of the top candidate drugs for the subgroups showed that most of these drugs are FDA-approved drugs for cancer, and others are non-cancer related, but have the potential to be repurposed for cancer. We have discovered novel cancer-related mechanisms that these drugs can target in different cancer types to reduce cancer treatment costs and improve patient survival. Further wet lab experiments to validate these findings are required prior to initiating clinical trials using these repurposed therapies.

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Sphingomyelin nanosystems loaded with uroguanylin and etoposide for treating metastatic colorectal cancer

Cited by 16 publications

References 54 publications

Effectiveness of a novel gene nanotherapy based on putrescine for cancer treatment

Effectiveness of a novel gene nanotherapy based on putrescine for cancer treatment

The nutritional functions of dietary sphingomyelin and its applications in food

Explainable artificial intelligence for patient stratification and drug repositioning

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