α-Conotoxin ImI-modified polymeric micelles as potential nanocarriers for targeted docetaxel delivery to α7-nAChR overexpressed non-small cell lung cancer

Abstract

A micelle system modified with α-Conotoxin ImI (ImI), a potently antagonist for alpha7 nicotinic acetylcholine receptor (α7-nAChR) previously utilized for targeting breast cancer, was constructed. Its targeting efficiency and cytotoxicity against non-small cell lung cancer (NSCLC) highly expressing α7-nAChR was investigated. A549, a non-small cell lung cancer cell line, was selected as the cell model. The cellular uptake study showed that the optimal modification ratio of ImI on micelle surface was 5% and ImI-modification increased intracellular delivery efficiency to A549 cells via receptor-mediated endocytosis. Intracellular Ca2+ transient assay demonstrated that ImI modification led to enhanced molecular interaction between nanocarriers and A549 cells. The in vivo near-infrared fluorescence imaging further revealed that ImI-modified micelles could facilitate the drug accumulation in tumor sites compared with non-modified micelles via α7-nAChR mediation. Moreover, docetaxel (DTX) was loaded in ImI-modified nanomedicines to evaluate its in vitro cytotoxicity. As a result, DTX-loaded ImI-PMs exhibited greater anti-proliferation effect on A549 cells compared with non-modified micelles. Generally, our study proved that ImI-modified micelles had targeting ability to NSCLC in addition to breast cancer and it may provide a promising strategy to deliver drugs to NSCLC overexpressing α7-nAChR.

Development of R 8 modified epirubicin–dihydroartemisinin liposomes for treatment of non-small-cell lung cancer

“…To investigate uptake in A549 cells, semi-quantitative flow cytometry was used [28]. Briefly, A549 cells (1.8 Â 10 5 cells/ well) were seeded in 6-well plates and cultured for 24 h at 37 C. A549 cells were treated with various drug-loaded liposomes at an epirubicin concentration of 10 mM (epirubicin/ dihydroartemisinin ¼ 1:5, molar ratio) and the culture medium was used as the blank control.…”

Cysteine [2,4] Disulfide Bond as a New Modifiable Site of α-Conotoxin TxIB

“…For example, VnIB is a specific ligand for human α6/α3β4 receptor with an IC 50 of 5.3 nM [ 7 ], [S9K]TxID has a specificity for mouse α3β4 nAChR [ 8 ] and GeXIVA can effectively inhibit α9α10 nAChR [ 9 ]. Recent research has shown that ImI-modified paclitaxel polymeric micelles can target non-small cell lung cancer tumor cells which overexpressed α7 nAChR [ 10 ]. α-Conotoxins are cysteine-rich peptides, with disulfide bonds to form the accurate pharmacophoric conformation.…”

Transcriptome Analysis of Ivosidenib-Mediated Inhibitory Functions on Non-Small Cell Lung Cancer

“…Lung carcinoma carries the highest incidence and mortality among cancers ( 1 ); we divide it into small cell and non-small cell lung cancer (NSCLC). Approximately 85% of lung carcinoma is NSCLC, which includes lung adenocarcinoma (40% of NSCLC), lung squamous cell carcinoma (40% of NSCLC), large cell carcinoma (10% of NSCLC), and other less common subtypes.…”