Fe3O4 magnetic nanoparticle-enhanced radiotherapy for lung adenocarcinoma via delivery of siBIRC5 and AS-ODN

Abstract

Background Radiotherapy is the mainstay treatment for lung adenocarcinoma, yet remains highly susceptible to resistance. Fe3O4 magnetic nanoparticles (MNPs) possess the ability to induce biological therapeutic effects. Herein, the current study set out to explore the effects of Fe3O4 MNPs on radiosensitivity of lung adenocarcinoma cells. Methods Fe3O4 MNPs loaded with both negatively-charged small interfering RNA against baculoviral IAP repeat containing 5 (siBIRC5) and oligodeoxynucleotide antisense (AS-ODN) to generate co-delivery NPs, followed by evaluation. Gel retardation assay was further performed to determine the binding ability of Fe3O4 MNPs to AS-ODN/siBIRC5. The radiosensitizing effect of NPs on lung adenocarcinoma cells was determined in the absence or the presence of NPs or radiotherapy. A549 and H460 tumor-bearing mice were established, where tumor tissues were subjected to immunohistochemistry. Results NPs were successfully prepared and characterized. BIRC5 expression levels were augmented in tissues of lung cancer patients. Fe3O4 MNPs enhanced the uptake of siBIRC5 and AS-ODN by lung adenocarcinoma cells. The presence of NPs under magnetic field reduced the BIRC5 expression and elevated the DR5 expression in lung adenocarcinoma cells. Lung adenocarcinoma cells treated with NPs exhibited inhibited tumor cell migration and increased DNA damage. After magnetic field treatment, tumors were better suppressed in the tumor-bearing mice treated with NPs, followed by radiotherapy. Conclusion Findings obtained in our study indicated that Fe3O4 MNPs-targeted delivery of siBIRC5 and AS-ODN enhances radiosensitivity, providing an innovative solution for the current clinically existing lung adenocarcinoma patients with radiotherapy resistance with a low risk of toxicity.

Establishing a prognostic model based on immune-related genes and identification of BIRC5 as a potential biomarker for lung adenocarcinoma patients

“…Finally, the functional phenotype of BIRC5 was further explored by preliminary experiments. The signi cant BIRC5 mRNA levels in LUAD tissues and cell lines were con rmed by cell experiments, which was consistent with several ndings obtained previously [47][48][49] . In addition, BIRC5 gene knockdown in LUAD cell lines was proven to signi cantly inhibit the activity and proliferation of cancer cells.…”

Magnetic Fields and Cancer: Epidemiology, Cellular Biology, and Theranostics

“…Ferrimagnetic glass-ceramic have been successfully used as thermo-seeds for a hyperthermic treatment of carcinoma cells in Sprague-Dawley rats [589], whereas magnetite cationic liposomes where used to generate hyperthermia on local tumors and lung metastases in a mouse model of osteosarcoma [590]. Spinel ferrite nanoparticles were successfully synthesized and used for MHT [591], whereas MIONs (such as crack-free ferrimagnetic maghemite, γ-Fe 2 O 3 ) may be useful for the in situ hyperthermic treatment of cancer [592][593][594][595]. SPIONs have been increasingly studied for their excellent MHT applications [596,597], whereas lanthanum-strontium manganite particles that were embellished with gold nanoparticles were found to be suitable for the treatment of deeper tumors [598].…”

153Sm-labeled Fe3O4@lapatinib nanoparticles as a potential therapeutic agent for breast cancer: synthesis, quality control, and in vivo evaluation

“…This size range is suitable for constructing targeted drug delivery systems for cancer treatment. 29 Larger magnetic particle diameters exceeding 100 nm are swiftly eliminated from the bloodstream by the mononuclear phagocyte system of the liver and spleen, and no particles are detected in other tissues. 30 Notably, the hydrodynamic size of Fe 3 O 4 @lapatinib- 153 Sm is larger than its size obtained from TEM images.…”