Targeting lung cancer cells with MUC1 aptamer-functionalized PLA-PEG nanocarriers

Abstract

MUC1 aptamer-functionalized PLA-PEG nanocarriers at various w/w ratios (polymer to doxorubicin weight ratio) were prepared by a double emulsion method. Physiochemical properties, encapsulation efficiency (EE), loading content (LC) and in vitro release kinetics of DOX were assessed. Furthermore, cytotoxicity and antitumor activity of prepared PLA-PEG-Apt/DOX NPs at w/w ratio 10:1 were evaluated by MTT assay and flow cytometry against MUC1-overexpressing A-549 cell line. Targeted nanocarriers (PLA-PEG-Apt/DOX NPs at w/w ratio 10:1) induced higher apoptosis rate (36.3 ± 3.44%) for 24 h in MUC1 positive A-549 cancer cells in compare to non-targeted form (PLA-PEG/DOX NPs at w/w ratio 10:1, 11.37 ± 1.65%) and free DOX (4.35 ± 0.81%). In other word, the percentage of cell death in A-549 lung cancer cells treated with PLA-PEG-Apt/DOX NPs at w/w ratio 10:1 is 3.19 and 8.34 fold higher than in non-targeted form and Free DOX treated cancer cells, respectively. Therefore, PLA-PEG-Apt/DOX NPs might be considered a promising drug delivery system for targeted drug delivery towards MUC1-overexpressing tumors cells.

Inhibiting Multidrug Resistance with Transferrin-Targeted Polymersomes through Optimization of Ligand Density

“…The cumulative release rates of PLA-F127-PLA/DOX polymersomes was 61.1% at pH 5.0 and 51.0% at pH 7.4. The biphasic pattern of the initial rapid release followed by slow release might be related to the embedding position of DOX, the drug concentration gradient between inside and outside the polymersomes, and the degradation of the polymer matrix. , The initial rapid release could result from the hydrophilic DOX adsorbed on the surface of polymersomes. With the slow degradation of polymer materials and the reduction of the drug concentration difference inside and outside the polymersomes, the release of DOX became slow.…”

Aptamers: Features, Synthesis and Applications

“…developed MUC1‐based PLA−PEG nanocarriers as a tumor‐targeted delivery system for the targeted delivery of DOX to MUC1‐positive cancer cells (PLA−PEG−Apt/DOX NPs). The studies showed that the aptamer resulted in enhanced cellular uptake of the PLA−PEG−Apt/DOX NPs to the cancer cells and delivery system for MUC1‐positive cancer cells [93] …”

“…The studies showed that the aptamer resulted in enhanced cellular uptake of the PLAÀ PEGÀ Apt/DOX NPs to the cancer cells and delivery system for MUC1-positive cancer cells. [93] Mesoporous silica nanoparticles (MSN) have drawn interest as a drug delivery system due to their large, adaptable surface, flexible pore volume, capacity to carry a variety of dosages and types of drugs, and good biocompatibility. [94] MUC1 is an important molecular target in cancer and it is a transmembrane glycoprotein that has been overexpressed in 70 % of breast cancers.…”

“…Drug Target A15 Salinomycin Hepatocellular cancer [91] CD44 RNA DOX Triple negative breast cancer [92] MUC1 DOX MUC1 positive cancer cells [93] C2NP DOX ALCL [98] AS1411 DOX ChemoÀ PTT [99] Gint4 DOX PDGFRβ [100] AS1411 5-FU Nucleolin [101]…”

A bimolecular modification strategy for developing long-lasting bone anabolic aptamer

“…Among these choices, PEG has emerged as the predominant option for enhancing the pharmacokinetics attributes and extending the circulation half-life of aptamer candidates in vivo . 11 , 12 , 13 , 14 , 15 Riccardi et al. engineered NU172-T H 9 with an extended in vivo half-life of 28.6 h through PEGylation, resulting in enhanced thrombin inhibitory activity.…”