Cisplatin loaded multiwalled carbon nanotubes reverse drug resistance in NSCLC by inhibiting EMT

Abstract

Background Lung cancer is one of the important health threats worldwide, of which 5-year survival rate is less than 15%. Non-small-cell lung cancer (NSCLC) accounts for about 80% of all lung cancer with high metastasis and mortality. Methods Cisplatin loaded multiwalled carbon nanotubes (Pt-MWNTS) were synthesized and used to evaluate the anticancer effect in our study. The NSCLC cell lines A549 (cisplatin sensitive) and A549/DDP (cisplatin resistant) were used in our in vitro assays. MTT was used to determine Cancer cells viability and invasion were measured by MTT assay and Transwell assay, respectively. Apoptosis and epithelial-mesenchymal transition related marker proteins were measured by western blot. The in vivo anti-cancer effect of Pt-MWNTs were performed in male BALB/c nude mice (4-week old). Results Pt-MWNTS were synthesized and characterized by X-ray diffraction, Raman, FT-IR spectroscopy and scan electron microscopy. No significant cytotoxicity of MWNTS was detected in both A549/DDP and A549 cell lines. However, Pt-MWNTS showed a stronger inhibition effect on cell growth than free cisplatin, especially on A549/DDP. We found Pt-MWNTS showed higher intracellular accumulation of cisplatin in A549/DDP cells than free cisplatin and resulted in enhanced the percent of apoptotic cells. Western blot showed that application of Pt-MWNTS can significantly upregulate the expression level of Bax, Bim, Bid, Caspase-3 and Caspase-9 while downregulate the expression level of Bcl-2, compared with free cisplatin. Moreover, the expression level of mesenchymal markers like Vimentin and N-cadherin was more efficiently reduced by Pt-MWNTS treatment in A549/DDP cells than free cisplatin. In vivo study in nude mice proved that Pt-MWNTS more effectively inhibited tumorigenesis compared with cisplatin, although both of them had no significant effect on body weight. Conclusion Pt-MWNT reverses the drug resistance in the A549/DDP cell line, underlying its possibility of treating NSCLC with cisplatin resistance.

Gelatin-Functionalized Carbon Nanotubes Loaded with Cisplatin for Anti-Cancer Therapy

“…Additionally, the needle-like structure of carbon nanotubes enables them to enter cells, aiding effective medication delivery and specific killing of tumor cells [ 24 , 25 ]. By possessing this ability, drugs can avoid premature inactivation, minimize damage to neighboring healthy cells, and postpone the emergence of chemoresistance [ 10 , 26 , 27 ].…”

“…Functionalized carbon nanotubes can enhance the cellular uptake of low-permeability drugs, thereby increasing their intracellular concentration and improving their efficacy [ 35 ]. Functionalizing the carbon nanotubes’ surface can also ameliorate chemotherapy-induced drug resistance while further improving the carbon nanotubes’ loading capacity [ 26 , 32 , 36 ]. We created a polydopamine (PDA) coating by self-polymerizing dopamine (DA) [ 37 ], comprising reactive groups that permit Michael’s addition reactions with gelatin (Gel) molecules.…”

Role and Mechanism of Exosome-Derived Long Noncoding RNA HOTAIR in Lung Cancer

“…Second, when confirmed, most patients were in the late lung cancer stage. According to statistical data, a 5 year survival rate of patients with lung cancer is only close to 15.9%. − Based on this, it is both urgent and challenging for researchers to seek potential molecular diagnostic biomarkers that are reliable and valuable.…”

Carbon Nanotubes as Carriers in Drug Delivery for Non-Small Cell Lung Cancer, Mechanistic Analysis of Their Carcinogenic Potential, Safety Profiling and Identification of Biomarkers

“…In addition, the MWCNTs caused the downregulation of mesenchymal markers such as vimentin and N-cadherin (N-cad) along with EMT-induced transcription factors such as Snail, Slug and Twist1 leading to the reversal of cisplatin resistance. 34 The cytotoxic effects of MWCNTs on NSCLC cells in vitro are presented in Table 1 .…”

“… Carboplatin Diameters of 50 to 80 nm and lengths of 10 to 20 μm TC-1 Loss of mitochondrial and metabolic activities along with increased ROS production [ 33 ] 9. Cisplatin ∼5–15 nm A549/DDP Involvement of apoptosis via the upregulation of Bax, Bim, Bid, Caspases 3 and 9 along with downregulation of vimentin and N-cad, Snail, Slug and Twist1 [ 34 ] …”