Synergism through combination of chemotherapy and oxidative stress-induced autophagy in A549 lung cancer cells using redox-responsive nanohybrids: A new strategy for cancer therapy
Journal
Biomaterials
Journal Volume
42
Pages
30-41
Date Issued
2015
Author(s)
Abstract
A combination of various therapeutic approaches has emerged as a promising strategy for cancer treatment. A safe and competent nano-delivery system is thus in urgent demand to facilitate the simultaneous transport of various therapeutic agents to cancer cells and a tumor region to achieve synergistic effect. Gold nanoparticles (GNPs) and mesoporous silica nanoparticle (MSNs) were fabricated herein as potential candidates for drug delivery. Serving as gatekeepers, GNPs (5nm in diameter) were attached onto the amino-functionalized MSNs (denoted as NMSNs) via a relatively weak gold-nitrogen bonding. The resulting nanohybrids (denoted as GCMSNs) were uptaken by cells, and the detachment of GNPs and subsequent intracellular drug release from NMSNs were achieved by competitive binding of intracellular glutathione to GNPs. In addition to the function of gatekeeping, GNPs also play another role as the oxidative stress elicitor. Our invitro studies revealed that GCMSNs induced higher oxidative stress in lung cancer cells (A549) than in normal cells (3T3-L1). This growth inhibitory effect found in the cancer cells was likely induced by mitochondria dysfunction originated from the GCMSN-induced, oxidative stress-triggered mitochondria-mediated autophagy. The redox-responsive nanohybrids were further loaded with camptothecin and the intensified synergistic therapeutic effects were observed associated with combined chemotherapy and oxidative stress strategy. The results clearly demonstrate that such unique nanohybrids hold great promise for selective and effective cancer treatments. ? 2014 Elsevier Ltd.
Subjects
Autophagy; Chemotherapy; Glutathione-mediated intracellular release; Gold nanoparticles capping; Mesoporous silica nanohybrid; Oxidative stress strategy
SDGs
Other Subjects
Biological organs; Cell death; Chemotherapy; Controlled drug delivery; Fiber optic sensors; Gold nanoparticles; Metal nanoparticles; Mitochondria; Nanostructured materials; Oxidative stress; Peptides; Silica; Silica nanoparticles; Targeted drug delivery; Autophagy; Competitive binding; Glutathiones; Gold nanoparticles (GNPs); Mesoporous silica nanoparticles; Mitochondria dysfunctions; Nano hybrids; Nano-delivery systems; Diseases; amino functionalized mesoporous silica nanoparticle; camptothecin; glutathione; gold; gold nanoparticle; gold nanoparticle capped mesoporous silica nanoparticle; nitrogen; silica nanoparticle; unclassified drug; antineoplastic agent; camptothecin; glutathione; malonaldehyde; nanoparticle; silicon dioxide; 3T3 cell line; A549 cell line; animal cell; animal experiment; animal model; animal tissue; antineoplastic activity; Article; autophagy; binding competition; cancer chemotherapy; cancer inhibition; cell level; chemical binding; controlled study; disorders of mitochondrial functions; drug delivery system; drug megadose; drug potentiation; drug release; human; human cell; in vitro study; internalization; lung cancer; male; mouse; multiple cycle treatment; nanofabrication; nonhuman; oxidation reduction state; oxidative stress; particle size; therapy effect; animal; autophagy; biological model; chemistry; drug effects; drug screening; energy metabolism; intracellular space; lipid peroxidation; metabolism; mitochondrion; Neoplasms; nude mouse; oxidation reduction reaction; oxidative stress; pathology; porosity; tumor cell line; ultrastructure; 3T3-L1 Cells; Animals; Antineoplastic Combined Chemotherapy Protocols; Autophagy; Camptothecin; Cell Line, Tumor; Energy Metabolism; Glutathione; Humans; Intracellular Space; Lipid Peroxidation; Malondialdehyde; Mice; Mice, Nude; Mitochondria; Models, Biological; Nanoparticles; Neoplasms; Oxidation-Reduction; Oxidative Stress; Porosity; Silicon Dioxide; Xenograft Model Antitumor Assays
Type
journal article