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1.
Sci Rep ; 14(1): 16941, 2024 07 23.
Artículo en Inglés | MEDLINE | ID: mdl-39043763

RESUMEN

The nonspecific nature of cancer drug delivery often results in substantial toxic side effects during treatments for breast cancer. To mitigate these negative outcomes, our approach involves loading methotrexate (MTX) within carbon quantum dots (CQDs) synthesized from folic acid, which are then enveloped in exosomal membranes obtained from breast cancer cells (Ex@MTX-CQDs). Analysis utilizing nanoparticle tracking techniques has demonstrated that these Ex@MTX-CQDs maintain the physical and biochemical properties of their exosomal precursors. The release profile of MTX indicated a restricted release percentage (less than 10%) under normal physiological conditions, which is contrasted by a more consistent release rate (approximately 65%) when emulating the conditions found within tumor tissues. The toxicological assessments have confirmed that the presence of exosomes combined with leftover folic acid significantly improves the delivery efficacy of MTX directly to the cancerous cells through the binding to folate and heparan sulfate proteoglycan receptors. This process results in increased disruption of the mitochondrial membrane potential and subsequently triggers apoptosis, ultimately leading to the destruction of cancerous cells. Our research could potentially contribute to the further innovation and application of nanocarriers derived from biological sources for the targeted treatment of breast cancer.


Asunto(s)
Neoplasias de la Mama , Carbono , Exosomas , Ácido Fólico , Metotrexato , Puntos Cuánticos , Humanos , Ácido Fólico/química , Puntos Cuánticos/química , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Exosomas/metabolismo , Femenino , Metotrexato/farmacología , Metotrexato/administración & dosificación , Metotrexato/química , Carbono/química , Portadores de Fármacos/química , Línea Celular Tumoral , Sistemas de Liberación de Medicamentos , Apoptosis/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/administración & dosificación , Ondas Ultrasónicas , Células MCF-7 , Potencial de la Membrana Mitocondrial/efectos de los fármacos
2.
Int J Biol Macromol ; 274(Pt 2): 133516, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38944078

RESUMEN

The recent challenge in enhancing the targeted delivery of anticancer drugs to cancer cells is improving the bioavailability and therapeutic efficacy of drug delivery systems while minimizing their systemic side effects. In this study, the MIL-88(Fe) metal-organic framework was synthesized using the in situ method in the presence of hydroxyapatite nanoparticles (HAP) toward the HAP/MIL-88(Fe) (HM) nanocomposite preparation. It was then functionalized with mannose (M) as an anticancer receptor through the Steglich esterification method. Various analyses confirmed the successful synthesis of MHM. For drug release investigation, 5-Fu was loaded into the MHM, which was then coated with a hyaluronic acid (HA) hydrogel film. Characterization analyses verified the structure of the resulting HA/5-Fu-MHM hydrogel film. In vitro drug release experiments showed that the release of 5-Fu drug from HA/5-Fu-MHM could be controlled with pH, reducing its release rate in the acidic environment of the stomach while increasing it in the intestinal environment. Cytotoxicity results of the HA/5-Fu-MHM hydrogel film against HT29 cancer cells showed enhanced cytotoxicity due to the mannose and hyaluronic acid in its structure, which triggers a dual-targeted drug delivery system. The obtained results indicate that the prepared hydrogel films can be a promising bio-platform for colon cancer treatment.


Asunto(s)
Antineoplásicos , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Durapatita , Fluorouracilo , Ácido Hialurónico , Hidrogeles , Manosa , Estructuras Metalorgánicas , Ácido Hialurónico/química , Humanos , Durapatita/química , Estructuras Metalorgánicas/química , Manosa/química , Fluorouracilo/farmacología , Fluorouracilo/química , Fluorouracilo/administración & dosificación , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/administración & dosificación , Hidrogeles/química , Portadores de Fármacos/química , Células HT29 , Administración Oral
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