Dataset Information

Self-Assembled Aptamer-Grafted Hyperbranched Polymer Nanocarrier for Targeted and Photoresponsive Drug Delivery.

ABSTRACT: Photoresponsive materials are emerging as ideal carriers for precisely controlled drug delivery owing to their high spatiotemporal selectivity. However, drawbacks such as slow release kinetics, inherent toxicity, and lack of targeting ability hinder their translation into clinical use. We constructed a new DNA aptamer-grafted photoresponsive hyperbranched polymer, which can self-assemble into nanoparticles, thereby achieving biocompatibility and target specificity, as well as light-controllable release behavior. Upon UV-irradiation, rapid release induced by disassembly was observed for Nile Red-loaded nanoparticles. Further in?vitro cell studies confirmed this delivery system's specific binding and internalization performance arising from the DNA aptamer corona. The DOX-loaded nanoassembly exhibited selective phototriggered cytotoxicity towards cancer cells, indicating its promising therapeutic effect as a smart drug delivery system.

SUBMITTER: Yang L

PROVIDER: S-EPMC6442708 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Self-Assembled Aptamer-Grafted Hyperbranched Polymer Nanocarrier for Targeted and Photoresponsive Drug Delivery.

Yang Lu L Sun Hao H Liu Yuan Y Liu Yuan Y Hou Weijia W Yang Yu Y Cai Ren R Cui Cheng C Zhang Penghui P Pan Xiaoshu X Li Xiaowei X Li Long L Sumerlin Brent S BS Tan Weihong W

Angewandte Chemie (International ed. in English) 20181126 52

Photoresponsive materials are emerging as ideal carriers for precisely controlled drug delivery owing to their high spatiotemporal selectivity. However, drawbacks such as slow release kinetics, inherent toxicity, and lack of targeting ability hinder their translation into clinical use. We constructed a new DNA aptamer-grafted photoresponsive hyperbranched polymer, which can self-assemble into nanoparticles, thereby achieving biocompatibility and target specificity, as well as light-controllable ...[more]

PMID: 30387923

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Project description:Synthetic nucleic acids have shown great potential in the treatment of various diseases. Nevertheless, the selective delivery to a target tissue has proved challenging. The coupling of nucleic acids to targeting peptides, proteins, and antibodies has been explored as an approach for their selective tissue delivery. Nevertheless, the preparation of covalently coupled peptides and proteins that can also undergo intracellular release as well as deliver more than one copy of the nucleic acid has proved challenging. Recently, we have developed a novel method for the rapid noncovalent conjugation of nucleic acids to targeting single chain antibodies (scFv) using chemically self-assembled nanostructures (CSANs). CSANs have been prepared by the self-assembly of two dihydrofolate reductase molecules (DHFR(2)) and a targeting scFv in the presence of bis-methotrexate (bis-MTX). The valency of the nanorings can be tuned from one to eight subunits, depending on the length and composition of the linker between the dihydrofolate reductase molecules. To explore their potential for the therapeutic delivery of nucleic acids as well as the ability to expand the capabilities of CSANs by incorporating smaller cyclic targeting peptides, we prepared DHFR(2) proteins fused through a flexible peptide linker to cyclic-RGD, which targets ?v?3 integrins, and a bis-MTX chemical dimerizer linked to an antisense oligonucleotide (bis-MTX-ASO) that has been shown to silence expression of eukaryotic translation initiation factor 4E (eIF4E). Monomeric and multimeric cRGD-CSANs were then prepared with bis-MTX-ASO and shown to undergo endocytosis in the breast cancer cell line, MDA-MB-231, which overexpresses ?v?3. The bis-MTX-ASO was shown to undergo endosomal escape resulting in the knock down of eIF4E with at least the same efficiency as ASO delivered by oligofectamine. The modularity, flexibility, and common method of conjugation may prove to be a useful general approach for the targeted delivery of ASOs, as well as other nucleic acids to cells.

Dataset Information

Self-Assembled Aptamer-Grafted Hyperbranched Polymer Nanocarrier for Targeted and Photoresponsive Drug Delivery.

Publications

Self-Assembled Aptamer-Grafted Hyperbranched Polymer Nanocarrier for Targeted and Photoresponsive Drug Delivery.

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