ABSTRACT
The use of multifunctional nanomedicines for image-guided drug delivery is currently being universally evaluated as a means of efficiently managing cancers and other diseases. In this study we evaluated the potential of an indocyanine green (ICG) and paclitaxel (PTX) loaded human serum albumin (HSA) nanoparticles that was conjugated with hyaluronic acid for use in image-guided drug delivery targeted to CD44-positive non-small cell lung cancer (NSCLC). Series of NSCLC cell lines were evaluated for the expression of CD44 using both western blot analysis and qRT-PCR and compared to a normal lung fibroblast cell line (MRC-5). Using Fluorescence microscopy and photoacoustic imaging (PA), we explored the ability of these targeted nanoparticles to selectively accumulate in NSCLC cell lines in comparison to MRC-5 and their potential for biomedical imaging towards their use for theranostic application. Results obtained suggest that these targeted nanoparticles have potential for application in both imaging and treatment of NSCLC.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Nanoparticles , Pharmaceutical Preparations , Carcinoma, Non-Small-Cell Lung/drug therapy , Cell Line, Tumor , Humans , Hyaluronan Receptors , Indocyanine Green , Lung Neoplasms/drug therapy , Paclitaxel/pharmacology , Serum Albumin, HumanABSTRACT
This study aimed to evaluate the anti-cancer effect of a combination therapy of miRNA-29b and genistein loaded in mucin-1 (MUC 1)-aptamer functionalized hybrid nanoparticles in non-small cell lung cancer (NSCLC) A549 cell line. Genistein-miRNA-29b-loaded hybrid nanoparticles (GMLHN) was prepared and characterized. Particle size and zeta potential were measured using photon correlation spectroscopy (PCS). Encapsulation efficiency and loading efficiency were determined using HPLC. Preferential internalization of MUC 1-aptamer functionalized GMLHN by A549 cells was evaluated and compared to normal MRC-5 cells. The ability of GMLHN to downregulate targeted oncoproteins Phosphorylated protein kinase, strain AK, Thymoma (Phosphorylated protein kinase B) (pAKT), Phosphorylated phosphoinositide 3-kinase (p-PI3K), DNA (cytosine-5-)-methyltransferase 3 beta (DNMT3B) and Myeloid Cell Leukemia Sequence 1 (MCL 1) was evaluated using western blot, while antiproliferative effect and ability to initiate apoptosis was also assessed in A549 cells. MUC 1-aptamer functionalized GMLHN nanoparticles were prepared. These nanoparticles were preferentially internalized by A549 cells but less so, in MRC-5 cells. pAKT, p-PI3K, DNMT3B and MCL 1 were efficiently downregulated by these nanoparticles without affecting the levels of AKT and PI3K in A549 cells. GMLHN demonstrated a superior antiproliferative effect compared to individual genistein and miRNA-29b-loaded nanoparticles. Results generated were able to demonstrate that genistein-miRNA-29b-loaded hybrid nanoparticles (GMLHN) could be a potential treatment modality for NSCLC because of the ability of the payloads to attack multiple targets.
ABSTRACT
The objective of this study was to evaluate the therapeutic efficacy and pharmacokinetic study of mucin1-aptamer functionalized miRNA-29b-loaded hybrid nanoparticles (MAFMILHNs) in lung tumor-bearing SCID mice. MAFMILHNs were manufactured using an isoelectric point based nanotechnology. They were then fully characterized for particle size, loading capacity, zeta potential, and encapsulation efficiency. The ability of MAFMILHNs to downregulate oncoprotein DNMT3B both at the cellular level and in vivo was monitored using Western blot, while the effect of the downregulation of DNMT3B on tumor growth was assessed using bioluminescence. Results indicate that the presence of MUC1-aptamer conjugated to the surface of the nanoparticles enhanced the selective delivery of miRNA-29b to tumor cells and tissues. Further, the downregulation of DNMT3B by MAFMILHNs resulted in the inhibition of tumor growth in mouse models.
