Stressing the Role of DNA as a Drug Carrier : Synthesis of DNA-Drug Conjugates through Grafting Chemotherapeutics onto Phosphorothioate Oligonucleotides
© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
| Veröffentlicht in: | Advanced materials (Deerfield Beach, Fla.). - 1998. - 31(2019), 16 vom: 15. Apr., Seite e1807533 |
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| 1. Verfasser: | |
| Weitere Verfasser: | , , , , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2019
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| Zugriff auf das übergeordnete Werk: | Advanced materials (Deerfield Beach, Fla.) |
| Schlagworte: | Journal Article cancer therapy drug conjugates drug delivery phosphorothioate spherical nucleic acid Antineoplastic Agents, Phytogenic Aptamers, Nucleotide Drug Carriers Fluorescent Dyes mehr... |
| Zusammenfassung: | © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. To stress the role of deoxyribonucleic acid (DNA) as a drug carrier, an efficient conjugation strategy in which chemotherapeutics can be grafted onto a phosphorothiolated DNA backbone through the reaction between the phosphorothioate group (PS) and a benzyl bromide group is proposed. As a proof of concept, benzyl-bromide-modified paclitaxel (PTX) is employed to graft onto the DNA backbone at the PS modification sites. Due to the easy preparation of phosphorothiolated DNA at any desired position during its solid-phase synthesis, diblock DNA strands containing both normal phosphodiester segment (PO DNA) and phosphorothiolate segment (PS DNA) are directly grafted with a multitude of PTXs without using complicated and exogenous linkers. Then, the resulting amphiphilic PO DNA-blocked-(PS DNA-grafted PTX) conjugates (PO DNA-b-(PS DNA-g-PTX)) assemble into PTX-loaded spherical nucleic acid (SNA)-like micellar nanoparticles (PTX-SNAs) with a high drug loading ratio up to ≈53%. Importantly, the PO DNA segment maintains its molecular recognition property and biological functions, which allows the as-prepared PTX-SNAs to be further functionalized with tumor-targeting aptamers, fluorescent probe strands, or antisense sequences. These multifunctional PTX-SNAs demonstrate active tumor-targeting delivery, efficient inhibition of tumor growth, and the reversal of drug resistance both in vitro and in vivo for comprehensive antitumor therapy |
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| Beschreibung: | Date Completed 08.08.2019 Date Revised 30.09.2020 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1521-4095 |
| DOI: | 10.1002/adma.201807533 |