scholarly journals Cancer Cell Membrane Decorated Silica Nanoparticle Loaded with miR495 and Doxorubicin to Overcome Drug Resistance for Effective Lung Cancer Therapy

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Jinyuan He ◽  
Chulian Gong ◽  
Jie Qin ◽  
Mingan Li ◽  
Shaohong Huang

Abstract Current cancer therapy usually succumbs to many extracellular and intracellular barriers, among which untargeted distribution and multidrug resistance (MDR) are two important difficulties responsible for poor outcome of many drug delivery systems (DDS). Here, in our study, the dilemma was addressed by developing a cancer cell membrane (CCM)-coated silica (SLI) nanoparticles to co-deliver miR495 with doxorubicin (DOX) for effective therapy of lung cancer (CCM/SLI/R-D). The homologous CCM from MDR lung cancer cells (A549/DOX) was supposed to increase the tumor-homing property of the DDS to bypass the extracellular barriers. Moreover, the MDR of cancer cells were conquered through downregulation of P-glycoprotein (P-gp) expression using miR495. It was proved that miR495 could significantly decrease the expression of P-gp which elevated intracellular drug accumulation in A549/DOX. The in vitro and in vivo results exhibited that CCM/SLI/R-D showed a greatly enhanced therapeutic effect on A549/DOX, which was superior than applying miR495 or DOX alone. The preferable effect of CCM/SLI/R-D on conquering the MDR in lung cancer provides a novel alternative for effective chemotherapy of MDR cancers.

Author(s):  
Jiongwei Pan ◽  
Gang Huang ◽  
Zhangyong Yin ◽  
Xiaoping Cai ◽  
Enhui Gong ◽  
...  

AbstractSignificantly high-expressed circFLNA has been found in various cancer cell lines, but not in lung cancer. Therefore, this study aimed to explore the role of circFLNA in the progression of lung cancer. The target gene of circFLNA was determined by bioinformatics and luciferase reporter assay. Viability, proliferation, migration, and invasion of the transfected cells were detected by CCK-8, colony formation, wound-healing, and transwell assays, respectively. A mouse subcutaneous xenotransplanted tumor model was established, and the expressions of circFLNA, miR-486-3p, XRCC1, CYP1A1, and related genes in the cancer cells and tissues were detected by RT-qPCR, Western blot, or immunohistochemistry. The current study found that miR-486-3p was low-expressed in lung cancer. MiR-486-3p, which has been found to target XRCC1 and CYP1A1, was regulated by circFLNA. CircFLNA was located in the cytoplasm and had a high expression in lung cancer cells. Cancer cell viability, proliferation, migration, and invasion were promoted by overexpressed circFLNA, XRCC1, and CYP1A1 but inhibited by miR-486-3p mimic and circFLNA knockdown. The weight of the xenotransplanted tumor was increased by circFLNA overexpression yet reduced by miR-486-3p mimic. Furthermore, miR-486-3p mimic reversed the effect of circFLNA overexpression on promoting lung cancer cells and tumors and regulating the expressions of miR-486-3p, XRCC1, CYP1A1, and metastasis/apoptosis/proliferation-related factors. However, overexpressed XRCC1 and CYP1A1 reversed the inhibitory effect of miR-486-3p mimic on cancer cells and tumors. In conclusion, circFLNA acted as a sponge of miR-486-3p to promote the proliferation, migration, and invasion of lung cancer cells in vitro and in vivo by regulating XRCC1 and CYP1A1.


2018 ◽  
Author(s):  
Norihiro Kotani ◽  
Arisa Yamaguchi ◽  
Tomoko Ohnishi ◽  
Ryusuke Kuwahara ◽  
Takanari Nakano ◽  
...  

ABSTRACTCancer-specific antigens expressed in the cell membrane have been used as targets for several molecular targeted strategies in recent years with remarkable success. To develop more effective cancer treatments, novel targets and strategies for targeted therapies are needed. Here, we examined the cancer cell membrane-resident “cis-bimolecular complex” as a possible cancer target (cis-bimolecular cancer target: BiCAT) using proximity proteomics, a technique that has attracted attention in recent years. BiCATs were detected using a previously developed method, termed the enzyme-mediated activation of radical source (EMARS), to label the components proximal to a given cell membrane molecule. EMARS analysis identified some BiCATs, such as close homolog of L1 (CHL1), fibroblast growth factor 3 (FGFR3) and α2 integrin, which are commonly expressed in mouse primary lung cancer cells and human lung squamous cell carcinoma cells. Analysis of cancer specimens from 55 lung cancer patients revealed that approximately half of patients were positive for these BiCATs. In vitro simulation of effective drug combinations used for multiple drug treatment strategy was performed using reagents targeted to BiCAT molecules. The combination treatment based on BiCAT information moderately suppressed cancer cell proliferation compared with single administration, suggesting that the information about BiCATs in cancer cells is profitable for the appropriate selection of the combination among molecular targeted reagents. Thus, BiCAT has the possibility to make a contribution to several molecular targeted strategies in future.


Nanomedicine ◽  
2019 ◽  
Vol 14 (18) ◽  
pp. 2461-2479
Author(s):  
Nayra M Kamel ◽  
Maged W Helmy ◽  
Magda W Samaha ◽  
Doaa Ragab ◽  
Ahmed O Elzoghby

Aim: Multicompartmental lipid–protein nanohybrids (MLPNs) were developed for combined delivery of the anticancer drugs tretinoin (TRE) and genistein (GEN) as synergistic therapy of lung cancer. Materials & methods: The GEN-loaded lipid core was first prepared and then coated with TRE-loaded zein shell via nanoprecipitation. Results: TRE/GEN-MLPNs demonstrated a size of 154.5 nm. In situ ion pair formation between anionic TRE and the cationic stearyl amine improved the drug encapsulation with enhanced stability of MLPNs. TRE/GEN-coloaded MLPNs were more cytotoxic against A549 cancer cells compared with combined free GEN/TRE. In vivo, lung cancer bearing mice treated with TRE/GEN-MLPNs displayed higher apoptotic caspase activation compared with mice-treated free combined GEN/TRE. Conclusion: TRE/GEN-MLPNs might serve as a promising parenteral nanovehicles for lung cancer therapy.


Nanomedicine ◽  
2020 ◽  
Vol 15 (27) ◽  
pp. 2689-2705
Author(s):  
Ming-Hsien Chan ◽  
Yung-Chieh Chan ◽  
Ru-Shi Liu ◽  
Michael Hsiao

Aim: To develop a micelle-type nanobubble decorated with fluorescein-5-isothiocyanate-conjugated transferrin, with encapsulation of paclitaxel (PTX@FT-NB) for lung cancer treatment. Materials & methods: PTX@FT-NBs were characterized to determine their physicochemical properties, structural stability and cytotoxicity. Lung cancer cell and mouse xenograft tumor models were used to evaluate the therapeutic effectiveness of PTX@FT-NB. Results: The PTX@FT-NBs not only showed selective targeting to lung cancer cells but also inhibited tumor growth significantly via paclitaxel release. Furthermore, paclitaxel-induced microtubule stabilization demonstrated the release of the drug from PTX@FT-NB in the targeted tumor cell both in vitro and in vivo. Conclusion: PTX@FT-NB has the potential as an anticancer nanocarrier against lung cancer cells because of its specific targeting and better drug delivery capacity.


2021 ◽  
Vol 118 (30) ◽  
pp. e2022769118
Author(s):  
Zhengwei Liu ◽  
Faming Wang ◽  
Xinping Liu ◽  
Yanjuan Sang ◽  
Lu Zhang ◽  
...  

The dynamic change of cell-surface glycans is involved in diverse biological and pathological events such as oncogenesis and metastasis. Despite tremendous efforts, it remains a great challenge to selectively distinguish and label glycans of different cancer cells or cancer subtypes. Inspired by biomimetic cell membrane–coating technology, herein, we construct pH-responsive azidosugar liposomes camouflaged with natural cancer-cell membrane for tumor cell–selective glycan engineering. With cancer cell–membrane camouflage, the biomimetic liposomes can prevent protein corona formation and evade phagocytosis of macrophages, facilitating metabolic glycans labeling in vivo. More importantly, due to multiple membrane receptors, the biomimetic liposomes have prominent cell selectivity to homotypic cancer cells, showing higher glycan-labeling efficacy than a single-ligand targeting strategy. Further in vitro and in vivo experiments indicate that cancer cell membrane–camouflaged azidosugar liposomes not only realize cell-selective glycan imaging of different cancer cells and triple-negative breast cancer subtypes but also do well in labeling metastatic tumors. Meanwhile, the strategy is also applicable to the use of tumor tissue–derived cell membranes, which shows the prospect for individual diagnosis and treatment. This work may pave a way for efficient cancer cell–selective engineering and visualization of glycans in vivo.


2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Yanxia Ma ◽  
Yu Liu ◽  
Linxin Teng ◽  
En Luo ◽  
Dekang Liu ◽  
...  

Lung cancer has become the leading cause of cancer-related death worldwide. Oxidative stress plays important roles in the pathogenesis of lung cancer. Many natural products show antioxidative activities in cancer treatment. Zi Shen decoction (ZSD) is a classic prescription for the treatment of lung disease. However, its effect on lung cancer lacks evidence-based efficacy. In this study, we investigated the anticancer effects of ZSD on lung cancer in vivo and in vitro. Our results showed that oral administration of ZSD suppressed the Lewis lung cancer (LLC) growth in a subcutaneous allograft model and promoted necrosis and inflammatory cell infiltration in the tumor tissues. Furthermore, ZSD not only inhibited tumor cell proliferation and migration but also induced cell apoptosis in lung cancer cells. PI3K/AKT signaling is well characterized in response to oxidative stress. The bioinformatics analysis and western blot assays suggested that ZSD decreased the enzyme activity of PI3K and AKT in vivo and in vitro. We also found that the AKT/GSK-3β/β-catenin pathway medicated anticancer effect of ZSD in lung cancer cells. In conclusion, we demonstrate for the first time that ZSD possesses antitumor properties, highlighting its potential use as an alternative strategy or adjuvant treatment for lung cancer therapy.


Sign in / Sign up

Export Citation Format

Share Document