Anti-MUC1 Aptamer/Negatively Charged Amino Acid Dendrimer Conjugates for Targeted Delivery to Human Lung Adenocarcinoma A549 Cells

Masuda, Marie; Kawakami, Shigeru; Wijagkanalan, Wassana; Suga, Tadaharu; Fuchigami, Yuki; Yamashita, Fumiyoshi; Hashida, Mitsuru

doi:10.1248/bpb.b16-00508

Cited by 24 publications

(4 citation statements)

References 11 publications

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“…Besides DLS and ELS, SLS technique is used for the first time in this study for determination of the conjugate’s molecular weight and estimation of efficiency of conjugation (the average number of aptamers which are successfully conjugated to a single ALGDG2). Various other methods are usually used in researches for determining the molecular weight of a specific composition or to compare and distinct different components by assessing their molar mass, such as gel permeation chromatography (GPC) 50 or polyacrylamide gel electrophoresis (PAGE) 51 , 52 . However, SLS is an accurate, simple and time-saving method for evaluating the average molar mass of nanostructures.…”

Section: Discussionmentioning

confidence: 99%

AS1411 Aptamer-Anionic Linear Globular Dendrimer G2-Iohexol Selective Nano-Theranostics

Mohammadzadeh

Cohan

Ghoreishi

et al. 2017

Sci Rep

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Molecular theranostics is of the utmost interest for diagnosis as well as treatment of different malignancies. In the present study, anionic linear globular dendrimer G2 is employed as a suitable carrier for delivery and AS1411 aptamer is exploited as the targeting agent to carry Iohexol specifically to the human breast cancer cells (MCF-7). Dendrimer G2 was prepared and conjugation of dendrimer and aptamer was carried out thereafter. Based on the data yielded by AFM, morphology of smooth and spherical non-targeted dendrimer changed to the rough aspherical shape when it conjugated. Then, conjugation was confirmed using DLS, ELS and SLS methods. Toxicity on nucleolin positive MCF-7 cells and nucleolin negative HEK-293 cells was assessed by XTT and apoptosis/necrosis assays. In vitro uptake was determined using DAPI-FITC staining and ICP-MS methods. In vivo studies including in vivo CT imaging, pathology and blood tests were done to confirm the imaging ability, bio-safety and targeted nature of the Nano-Theranostics in vivo. In a nutshell, the prepared construction showed promising effects upon decreasing the toxicity of Iohexol on normal cells and accumulation of it in the cancer tumors as well as reducing the number of cancer cells.

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Section: Discussionmentioning

confidence: 99%

AS1411 Aptamer-Anionic Linear Globular Dendrimer G2-Iohexol Selective Nano-Theranostics

Mohammadzadeh

Cohan

Ghoreishi

et al. 2017

Sci Rep

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“…Figure 1(B) shows that the β-elemene to PTX mass ratios did not significantly influence zeta potential; however, the zeta potential of SYL3C/EP-MEs is obviously lower than that of EP-MEs at their corresponding mass ratios. This could be a result of the negative charge of the DNA-based SYL3C aptamer modified outside the microemulsion (Masuda et al., 2016). As shown in Figure 1(C), the EE of PTX was significantly different with various mass ratios.…”

Section: Resultsmentioning

confidence: 99%

SYL3C aptamer-anchored microemulsion co-loading β-elemene and PTX enhances the treatment of colorectal cancer

Zhou

Cao

et al. 2019

Drug Delivery

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The aim of this study is to construct a SYL3C aptamer-anchored microemulsion based on b-elemene and PTX (SYL3C/EP-MEs) for enhancement on colorectal cancer therapy. Such microemulsion is consist of encapsulated drugs (b-elemene and PTX), tumor targeting ligand (3'-end thiolated SYL3C aptamer), thiol conjugated site (maleimide-modified PEGylated 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine, mal-DOPE-PEG), pH-sensitive component (DOPE) and other necessary excipients. SYL3C/EP-MEs showed a spherical particle with an average particle size around 30 nm and a high encapsulation efficiency (>80%) for both drugs. b-elemene and PTX could be released controllably from SYL3C/EP-MEs as pH values changed. SYL3C/EP-MEs displayed a selective affinity to HT-29 cells, leading to an obvious increase in cellular uptake, cell apoptosis and cytotoxicity. In the HT-29 tumor xenograft-bearing nude mice model studies, SYL3C/EP-MEs showed an overwhelming tumor growth inhibition, the longest survival time and the lowest systemic toxicity among all the treatments. The potential mechanism of enhanced anti-cancer ability was probably associated with the induction of M1 macrophage polarization, the downregulation of mutant p53 protein and the reduction of bcl-2 protein expression. Collectively, the microemulsion codelivery of b-elemene and PTX using functionalization with SYL3C aptamer provides a novel approach for combinational colorectal cancer-targeted treatment.

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“…Miyano et al developed a negatively charged sixth-generation amino acid dendrimer- KG6E, based on glutamic acid-modified dendritic poly(L-lysine) system [ 72 ]. Further modification of KG6E was done by conjugating an anti-mucin 1 (MUC1) aptamer by Masuda et al in a separate study for the targeted drug delivery to lung cancer A549 cells which express high levels of MUC1 [ 73 ]. The aptamer was extended by 20 adenine nucleotides to extrude it and ensure access for efficient binding to MUC1.…”

Section: Aptamer-modified Nanoconstructs In Cancer Therapymentioning

confidence: 99%

Advanced cancer targeting using aptamer functionalized nanocarriers for site-specific cargo delivery

Narwade¹,

Shaikh

Gajbhiye³

et al. 2023

Biomater Res

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The non-specificity of standard anticancer therapies has profound detrimental consequences in clinical treatment. Therapeutic specificity can be precisely achieved using cutting-edge ligands. Small synthetic oligonucleotide-ligands chosen through Systematic evolution of ligands by exponential enrichment (SELEX) would be an unceasing innovation in using nucleic acids as aptamers, frequently referred to as "chemical antibodies.” Aptamers act as externally controlled switching materials that can attach to various substrates, for example, membrane proteins or nucleic acid structures. Aptamers pose excellent specificity and affinity for target molecules and can be used as medicines to suppress tumor cell growth directly. The creation of aptamer-conjugated nanoconstructs has recently opened up innovative options in cancer therapy that are more effective and target tumor cells with minor toxicity to healthy tissues. This review focuses on a comprehensive description of the most capable classes of aptamer-tethered nanocarriers for precise recognition of cancer cells with significant development in proficiency, selectivity, and targetability for cancer therapy. Existing theranostic applications with the problems and future directions are also highlighted. Graphical Abstract

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Anti-MUC1 Aptamer/Negatively Charged Amino Acid Dendrimer Conjugates for Targeted Delivery to Human Lung Adenocarcinoma A549 Cells

Cited by 24 publications

References 11 publications

AS1411 Aptamer-Anionic Linear Globular Dendrimer G2-Iohexol Selective Nano-Theranostics

AS1411 Aptamer-Anionic Linear Globular Dendrimer G2-Iohexol Selective Nano-Theranostics

SYL3C aptamer-anchored microemulsion co-loading β-elemene and PTX enhances the treatment of colorectal cancer

Advanced cancer targeting using aptamer functionalized nanocarriers for site-specific cargo delivery

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