as-1411 and Carcinoma--Non-Small-Cell-Lung

The present work was developed the pH dependent-aptamer AS1411 (APT) decorated and erlotinib (En) loaded chitosan nanoparticles (CSNPs) for promising non-small-cell lung carcinoma (NSCLC) treatment. The characterization studies revealed that formulated APT-En-CSNPs were spherical in shape with size of 165.95 d. nm and PDI of 0.212. FTIR spectrum recorded molecular chemical interactions with composition of En or En-CSNPs. Cell viability assay, flow cytometry and fluorescent microscopy results revealed that APT-En-CSNPs triggered cancer cell death through pH-sensitive and nucleolin receptor-targeted release of En. The decoration of the APT improved the cellular uptake of En as evidenced by cellular sensing fluorescence and BioTEM assay. The APT-En-CSNPs induced the apoptosis through excessive ROS generation, nucleus damage and Δψm loss in the A549 cells. Hence, the present study revealed that the APT-En-CSNPs improved the therapeutic efficiency of En in NSCLC through the nucleolin targeted drug release.

Topics: A549 Cells; Animals; Apoptosis; Aptamers, Nucleotide; Carcinoma, Non-Small-Cell Lung; Cell Survival; Chitosan; Drug Carriers; Drug Liberation; Erlotinib Hydrochloride; Humans; Lung Neoplasms; Membrane Potential, Mitochondrial; Mice; Nanoparticles; NIH 3T3 Cells; Oligodeoxyribonucleotides; Reactive Oxygen Species; Signal Transduction

Molecularly targeted drug delivery systems represent a novel therapeutic strategy in the treatment of different cancers. In the present study, we have developed gemcitabine (GEM)-loaded AS1411 aptamer surface-decorated polyethylene glycol-poly(lactic-co-glycolic acid) nanopolymersome (Apt-GEM-NP) to target nucleolin-overexpressing non-small cell lung cancer (NSCLC; A549). The prepared Apt-GEM-NP showed average particle size of 128 ± 5.23 nm and spherical morphology with encapsulation efficiency and loading content of 95.32 ± 2.37% and 8.61 ± 0.27%, respectively. Apt-GEM-NP exhibited a controlled release pattern. A sustained release of drug in physiological conditions will greatly improve the chemotherapeutic efficiency of a system. Enhanced cellular uptake and the cytotoxicity of aptamer-conjugated nanoparticles (NPs) in A549 cancer cells obviously verified nucleolin-mediated receptor-based active targeting. Nucleolin-mediated internalization of the targeted polymeric NP was further confirmed by flow cytometry and fluorescence microscopy. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay clearly showed the enhanced cell proliferation inhibitory effect of AS1411-conjugated NP on account of the selective delivery of GEM to the nucleolin-overexpressing cancer cells. Our results showed that AS1411 aptamer conjugation on the surface of NP could be a potential treatment strategy for A549 as a nucleolin-overexpressing cell line. This suggests that AS1411-GEM-NPs could be potentially used for the treatment of NSCLC.

Topics: A549 Cells; Animals; Antimetabolites, Antineoplastic; Aptamers, Nucleotide; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; CHO Cells; Cricetinae; Cricetulus; Deoxycytidine; Drug Delivery Systems; Gemcitabine; Humans; Lung Neoplasms; Nanoparticles; Oligodeoxyribonucleotides; Polyesters; Polyethylene Glycols; Polymers