Drug-delivery and biological activity in colorectal cancer of a supramolecular porous material assembled from heptameric chromium-copper-adenine entities

• Published in: Journal of materials chemistry. B, Materials for biology and medicine Materials for biology and medicine, 2024-11, Vol.12 (43), p.11156-11164
• Main Authors: Mena-Gutiérrez, Sandra, Maiza-Razkin, Ekain, Pascual-Colino, Jon, Araúzo-Bravo, Marcos J, Beobide, Garikoitz, Castillo, Oscar, Castellanos-Rubio, Ainara, Gerovska, Daniela, Luque, Antonio, Pérez-Yáñez, Sonia
• Format: Article
• Language: English
• Subjects: 5-Fluorouracil; Adenine; Adenine - chemistry; Adenine - pharmacology; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biological activity; Cancer; Cell Proliferation - drug effects; Cell Survival - drug effects; Cholesterol; Chromium; Chromium - chemistry; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Controlled release; Copper - chemistry; Cytotoxicity; Degradation; Desorption; Drug Carriers - chemistry; Drug delivery; Drug Delivery Systems; Drug Screening Assays, Antitumor; Fluorouracil - chemistry; Fluorouracil - pharmacology; Half-life; Humans; Magnetic properties; Metal-organic frameworks; Metal-Organic Frameworks - chemistry; Metal-Organic Frameworks - pharmacology; Molecular Structure; Overexpression; Particle Size; Pore size; Porosity; Porous materials; Raffinose; Surface Properties; Theophylline; Toxicity; Transcriptomics; Water stability; Zeolites
• ISSN: 2050-750X; 2050-7518; 2050-7518
• DOI: 10.1039/d4tb01521e

The therapeutic application of drugs often faces challenges due to non-specific distribution, inadequate dosification and degradation, which limits their efficacy. Two primary strategies are employed to overcome these issues: the use of derivatives of the active substances and incorporation of those into porous materials. The latter, involving materials such as zeolites, metal-organic frameworks (MOFs), and hydrogels, has shown promising results in protecting the active ingredients from degradation and enabling a controlled release. This study focuses on supramolecular metal-organic frameworks (SMOFs), which leverage supramolecular interactions for enhanced pore size control. [Cu 6 Cr(μ-adeninato-κ N 3:κ N 9) 6 (μ 3 -OH) 6 (μ-OH 2 ) 6 ](SO 4 ) 1.5 · n H 2 O ( Cu6Cr ) was chosen for its flexible porous structure, water-stability, and paramagnetic properties. Magnetic sustentation studies showed that this compound was able to capture several drug molecules: 5-fluorouracil (5-FU), 5-aminosalicylic acid (5-ASA), 4-aminosalicylic acid (4-ASA) and theophylline (THEO). Their release follows a pseudo-first-order kinetics with desorption half-lives ranging from 2.2 to 4.7 hours. In this sense, a novel approach is proposed using bulkier raffinose and cholesterol as pore-blocking molecules. Cholesterol exhibited the best performance as a blocking molecule increasing the desorption half-life up to 8.2 hours. Cytotoxicity and RNA-seq transcriptomic assays carried out on human colorectal cancer cell cultures showed, on one hand, that the Cu6Cr porous material exhibits a proliferative effect, probably coming from the over-expression of MIR1248 and SUMO2 genes, and on the other hand, that there is a delay in the emergence of the cytotoxicity of 5-FU as expected for a slower release. Supramolecular metal-organic porous materials as drug delivery systems, modulation of the release kinetics using cholesterol as pore blocking agent and its impact on colorectal cancer cell cultures: cytotoxicity and RNA-seq transcriptomics studies.