LDH-Indomethacin Nanoparticles Antitumoral Action: A Possible Coadjuvant Drug for Cancer Therapy.
Kelly Costa AlvesCarlos Emmerson Ferreira da CostaCláudio Márcio Rocha RemédiosDanielle Queiroz CalcagnoMarcelo de Oliveira LimaJosé Rogério A SilvaCláudio Nahum AlvesPublished in: Molecules (Basel, Switzerland) (2024)
Indomethacin (INDO) has a mechanism of action based on inhibiting fatty acids cyclooxygenase activity within the inflammation process. The action mechanism could be correlated with possible anticancer activity, but its high toxicity in normal tissues has made therapy difficult. By the coprecipitation method, the drug carried in a layered double hydroxides (LDH) hybrid matrix would reduce its undesired effects by promoting chemotherapeutic redirection. Therefore, different samples containing INDO intercalated in LDH were synthesized at temperatures of 50, 70, and 90 °C and synthesis times of 8, 16, 24, and 48 h, seeking the best structural organization. X-ray diffraction (XRD), vibrational Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), spectrophotometric analysis in UV-VIS, and differential thermogravimetric analysis (TGA/DTA) were used for characterization. Our results indicate that higher temperatures and longer synthesis time through coprecipitation reduce the possibility of INDO intercalation. However, it was possible to establish a time of 16 h and a temperature of 50 °C as the best conditions for intercalation. In vitro results confirmed the cell viability potential and anticancer activity in the LDH-INDO sample (16 h and 50 °C) for gastric cancer (AGP01, ACP02, and ACP03), breast cancer (MDA-MB-231 and MCF-7), melanoma (SK-MEL-19), lung fibroblast (MRC-5), and non-neoplastic gastric tissue (MN01) by MTT assay. Cell proliferation was inhibited, demonstrating higher and lower toxicity against MDA-MB-231 and SK-MEL-19. Thus, a clinical redirection of INDO is suggested as an integral and adjunctive anticancer medication in chemotherapy treatment.
Keyphrases
- electron microscopy
- oxidative stress
- cell proliferation
- breast cancer cells
- cancer therapy
- high resolution
- fatty acid
- drug delivery
- healthcare
- signaling pathway
- adverse drug
- squamous cell carcinoma
- gene expression
- high throughput
- cell cycle
- computed tomography
- mass spectrometry
- nitric oxide
- oxide nanoparticles
- density functional theory
- molecular dynamics
- drug induced
- young adults
- electronic health record
- smoking cessation
- molecular dynamics simulations
- rectal cancer
- room temperature
- chemotherapy induced