Novel Chemo-Photothermal Therapy in Breast Cancer Using Methotrexate-Loaded Folic Acid Conjugated Au@SiO2 Nanoparticles

Abstract

Low level laser therapy (LLLT) is known as a safe type of phototherapy to target tumor tissue/cells. Besides, using targeted nanoparticles increases the successfulness of cancer therapy. This study was designed for investigating the combined effect of folate (FA)/Methotrexate (MTX) loaded silica coated gold (Au@SiO 2) nanoparticles (NPs) and LLLT on the fight against breast cancer. NPs were synthesized and characterized using FTIR, TEM and DLS-Zeta. The NPs had spherical morphology with mean diameter of around 25 nm and positive charge (+13.3 mV) while after conjugation with FA and MTX their net charge reduced to around-19.7 mV. Our findings in cell uptake studies clearly showed enhanced cellular uptake of NPs after FA and MTX loaded NPs in both breast cancer cell lines especially on MDA-MB-231 due to high expression of folate receptors. The results indicated that LLLT had a proliferative effect on both breast cancer cell lines but in the presence of engineered breast cancer targeted nanoparticle, the efficacy of combination chemo-photothermal therapy was significantly increased using MTT assay (p<0.05), DAPI staining, and cell cycle findings. The highest apoptotic effect on breast cancer cell lines was observed in the cells exposed to a combination of MTX-FA loaded Au@SiO 2 NP and LLLT proved by DAPI staining and cell cycle(by increasing the cell arrest in subG0/G1). Taken together a combination of chemotherapy and LLLT improves the potential of breast cancer therapy with minimum side effects.

Understanding nanoparticle endocytosis to improve targeting strategies in nanomedicine

“…Functionalization of NPs with FA could enhance NPs uptake in cancer cells as a specific targeting approach. [338][339][340] FA was conjugated to MSNs loaded with the chemotherapeutic drug topotecan and delivered to retinoblastoma cells. The FA-conjugated NPs exhibited higher uptake in retinoblastoma cells compared to that of non-conjugated NPs.…”

Effect of Cetuximab-Conjugated Gold Nanoparticles on the Cytotoxicity and Phenotypic Evolution of Colorectal Cancer Cells

“…Gold nanoparticles (AuNPs) have found a wide range of biomedical applications (e.g., drug delivery, diagnostics, biosensing, bio-imaging, and theranostics) due to their appealing features, including high biocompatibility and facile conjugation to biomolecules. Previous results have shown that drugs conjugated with AuNPs may significantly increase chemosensitivity and delivery efficacy in a variety of cancer types including colorectal cancer, oral squamous cell carcinoma, pancreatic cancer, breast cancer, and prostate cancer [ 22 , 23 , 24 , 25 , 26 , 27 ]. In recent years, an increasing number of studies were performed on the interaction of cetuximab-conjugated AuNPs (cetuximab-AuNPs) against EGFR-overexpressing cancers.…”

Solutions to the Drawbacks of Photothermal and Photodynamic Cancer Therapy

“…Another method to enhance specific targeting ability is to load tumor targeting ligands on nanoparticles, so that the nanoparticles can tightly bind to tumor cells. The most widely used targeting ligands include folic acid [ 43–47 ] and hyaluronic acid, [ 48–50 ] since their receptors are over‐expressed in most solid tumors due to rapid growth characteristics of malignant tumors. Some special receptors only express on the surface of certain types of tumor cells.…”