Targeted delivery of quercetin loaded mesoporous silica nanoparticles to the breast cancer cells

• Published in: Biochimica et biophysica acta Vol. 1860; no. 10; pp. 2065 - 2075
• Main Authors: Sarkar, Abhijit, Ghosh, Shatadal, Chowdhury, Sayantani, Pandey, Bhawna, Sil, Parames C.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2016
• Subjects: adenocarcinoma; Animals; antineoplastic agents; Apoptosis; Apoptosis - drug effects; bioavailability; Biodistribution; Breast cancer; breast neoplasms; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; cell cycle checkpoints; Cell Survival - drug effects; cell viability; confocal microscopy; Drug Delivery Systems; Ex-ovo; Female; flow cytometry; Folic acid; Folic Acid - administration & dosage; Folic Acid - chemical synthesis; Folic Acid - chemistry; Fourier transform infrared spectroscopy; Humans; image analysis; immunoblotting; MCF-7 Cells; Mice; Nanoparticle; nanoparticles; Nanoparticles - administration & dosage; Nanoparticles - chemistry; neoplasm cells; Porosity; porous media; quercetin; Quercetin - administration & dosage; Quercetin - chemistry; receptors; scanning electron microscopy; signal transduction; silica; Silicon Dioxide - chemistry; tissue repair; transmission electron microscopy; water solubility; Xenograft Model Antitumor Assays; RITC; Ex-ovo; EDC; Nanoparticle; HRP; APTES; DLS; MTT; CTAB; Biodistribution; RIPA; Folic acid; MSN-Q; MSN-FA-Q; Q; DDS; FITC; FBS; FTIR; MSN-FA; NADP; FESEM; MSN; Breast cancer; CAM; ECL; SDS-PAGE; TEOS; FA; TEM; Apoptosis
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2016.07.001

Mesoporous silica nanoparticles (MSNs) have been promising vehicles for drug delivery. Quercetin (Q), a natural flavonoid, has been reported to have many useful effects. However, poor water solubility as well as less bioavailability has confined its use as a suitable anti-cancer drug. Therefore, profound approach is required to overcome these drawbacks. We have synthesized folic acid (FA) armed mesoporous silica nanoparticles (MSN-FA-Q) loaded with quercetin and then characterized it by DLS, SEM, TEM and FTIR. MTT, confocal microscopy, flow cytometry, scratch assay and immunoblotting were employed to assess the cell viability, cellular uptake, cell cycle arrest, apoptosis, wound healing and the expression levels of different signalling molecules in breast adenocarcinoma cells. Nanoparticle distribution was investigated by using ex vivo optical imaging and CAM assay was employed to assess tumor regression. MSN-FA-Q facilitates higher cellular uptake and allows more drug bioavailability to the breast cancer cells with over-expressed folate receptors. Our experimental results suggest that the newly synthesized MSN-FA-Q nanostructure caused cell cycle arrest and apoptosis in breast cancer cells through the regulation of Akt & Bax signalling pathways. Besides, we also observed that MSN-FA-Q has a concurrent anti-migratory role as well. This uniquely engineered quercetin loaded mesoporous silica nanoparticle ensures a targeted delivery with enhanced bioavailability. Effective targeted therapeutic strategy against breast cancer cells. •Folic acid tagged quercetin loaded mesoporous silica nanoparticles was synthesized.•Higher uptake of folic acid tagged nanoparticle was observed in MDA MB231 cells than MCF 7 cells.•Tumor regression was studied in an ex-ovo model.•Quercetin loaded mesoporous silica nanoparticle ensures a targeted delivery with enhanced bioavailability.