Methotrexate-Loaded Surface-Modified Solid Lipid Nanoparticles Targeting Cancer Expressing COX-2 Enzyme

Area of Science:

• Nanotechnology
• Materials Science
• Biomedical Engineering

Background:

• Cancer is a leading global cause of death, necessitating novel therapeutic strategies.
• Targeting cancer cells overexpressing cyclooxygenase-2 (COX-2) is a key strategy in developing effective treatments.
• Solid lipid nanoparticles (SLNs) offer a promising platform for drug delivery in cancer therapy.

Purpose of the Study:

• To develop and characterize methotrexate-loaded, surface-modified SLNs using a novel lipid (C14-AAP) for targeted cancer therapy.
• To evaluate the in vitro and in vivo efficacy of these targeted SLNs against human breast (MCF7) and lung (A549) cancer cells.
• To assess the potential of AAP-modified SLNs as a chemotherapeutic formulation.

Main Methods:

• Preparation and characterization of C14-AAP modified SLNs using DLS, DSC, PXRD, UV-vis, HRTEM, and FESEM.
• In vitro cytotoxicity assessment via MTT assay, flow cytometry, and clonogenic assays on MCF7 and A549 cell lines.
• RT-PCR for COX-2 expression analysis, radiolabeling with 99mTc, and in vivo biodistribution studies in mice using SPECT/CT imaging.

Main Results:

• High COX-2 expression was confirmed in both MCF7 and A549 cancer cell lines.
• Methotrexate-loaded, AAP-modified SLNs demonstrated superior efficacy in cell killing and apoptosis induction compared to free methotrexate.
• Radiolabeled SLNs showed good stability (%RCP > 95%) and moderate tumor uptake in vivo, correlating with SPECT/CT imaging.

Conclusions:

• C14-AAP modified SLNs effectively target COX-2 overexpressing cancer cells.
• Surface-modified SLNs loaded with methotrexate represent a potent chemotherapeutic formulation with enhanced efficacy.
• This targeted nanoparticle approach holds significant potential for advancing cancer therapy.