Dual stimuli-responsive release of aptamer AS1411 decorated erlotinib loaded chitosan nanoparticles for non-small-cell lung carcinoma therapy

Kandasamy Saravanakumar; Anbazhagan Sathiyaseelan; Arokia Vijaya Anand Mariadoss; Elango Jeevithan; Xiaowen Hu; Sukjin Shin; Myeong-Hyeon Wang

doi:10.1016/j.carbpol.2020.116407

Dual stimuli-responsive release of aptamer AS1411 decorated erlotinib loaded chitosan nanoparticles for non-small-cell lung carcinoma therapy

Carbohydr Polym. 2020 Oct 1:245:116407. doi: 10.1016/j.carbpol.2020.116407. Epub 2020 May 20.

Authors

Kandasamy Saravanakumar¹, Anbazhagan Sathiyaseelan¹, Arokia Vijaya Anand Mariadoss¹, Elango Jeevithan², Xiaowen Hu¹, Sukjin Shin¹, Myeong-Hyeon Wang³

Affiliations

¹ Department of Medical Biotechnology, College of Biomedical Sciences, Kangwon National University, Chuncheon, 200-701, South Korea.
² Department of Marine Bio-Pharmacology, College of Food Science and Technology, Shanghai Ocean University, Shanghai, 201306, China.
³ Department of Medical Biotechnology, College of Biomedical Sciences, Kangwon National University, Chuncheon, 200-701, South Korea. Electronic address: mhwang@kangwon.ac.kr.

PMID: 32718591
DOI: 10.1016/j.carbpol.2020.116407

Abstract

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.

Keywords: Aptamer; Cancer therapy; Chitosan; Drug delivery; Erlotinib; Nanoparticles.

MeSH terms

A549 Cells
Animals
Apoptosis / drug effects
Aptamers, Nucleotide / chemistry*
Carcinoma, Non-Small-Cell Lung / metabolism*
Carcinoma, Non-Small-Cell Lung / pathology
Cell Survival / drug effects
Chitosan / chemistry*
Drug Carriers / administration & dosage*
Drug Carriers / chemistry
Drug Liberation
Erlotinib Hydrochloride / administration & dosage*
Erlotinib Hydrochloride / chemistry
Humans
Lung Neoplasms / metabolism*
Lung Neoplasms / pathology
Membrane Potential, Mitochondrial / drug effects
Mice
NIH 3T3 Cells
Nanoparticles / administration & dosage*
Nanoparticles / chemistry
Oligodeoxyribonucleotides / chemistry*
Reactive Oxygen Species / metabolism
Signal Transduction / drug effects

Substances

AGRO 100
Aptamers, Nucleotide
Drug Carriers
Oligodeoxyribonucleotides
Reactive Oxygen Species
Chitosan
Erlotinib Hydrochloride