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Enzymatic Synthesis of Aptamer-Polynucleotide Nanoparticles with High Anticancer Drug Loading for Targeted Delivery.

Publication ,  Journal Article
Deshpande, S; Yang, Y; Zauscher, S; Chilkoti, A
Published in: Biomacromolecules
January 2024

We report a targeted prodrug delivery platform that can deliver a cytostatic nucleobase analog with high drug loading. We chose fluorouracil (5FU), a drug used to treat various cancers, whose active metabolite 5-fluorodeoxyuridine monophosphate (5-FdUMP) is the antineoplastic agent. We use terminal deoxynucleotidyl transferase (TdT) to polymerize 5-fluorodeoxyuridine triphosphate (5-FdUTP) onto the 3'-end of an aptamer. We find that (i) addition of hydrophobic, unnatural nucleotides at the 3'-end of the 5-FdU polynucleotide by TdT leads to their spontaneous self-assembly into nuclease resistant micelles, (ii) aptamers presented on the micelle corona retain specificity for their cognate receptor on tumor cells, and (iii) the micelles deliver 5FU to tumor cells and exhibit greater cytotoxicity than the free drug. The modular design of our platform, consisting of a targeting moiety, a polynucleotide drug, and a self-assembly domain, can be adapted to encompass a range of polymerizable therapeutic nucleotides and targeting units.

Duke Scholars

Published In

Biomacromolecules

DOI

EISSN

1526-4602

ISSN

1525-7797

Publication Date

January 2024

Volume

25

Issue

1

Start / End Page

155 / 164

Related Subject Headings

  • Polynucleotides
  • Polymers
  • Nanoparticles
  • Micelles
  • Fluorouracil
  • Drug Delivery Systems
  • Cell Line, Tumor
  • Antineoplastic Agents
  • 40 Engineering
  • 34 Chemical sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Deshpande, S., Yang, Y., Zauscher, S., & Chilkoti, A. (2024). Enzymatic Synthesis of Aptamer-Polynucleotide Nanoparticles with High Anticancer Drug Loading for Targeted Delivery. Biomacromolecules, 25(1), 155–164. https://doi.org/10.1021/acs.biomac.3c00888
Deshpande, Sonal, Yunqi Yang, Stefan Zauscher, and Ashutosh Chilkoti. “Enzymatic Synthesis of Aptamer-Polynucleotide Nanoparticles with High Anticancer Drug Loading for Targeted Delivery.Biomacromolecules 25, no. 1 (January 2024): 155–64. https://doi.org/10.1021/acs.biomac.3c00888.
Deshpande S, Yang Y, Zauscher S, Chilkoti A. Enzymatic Synthesis of Aptamer-Polynucleotide Nanoparticles with High Anticancer Drug Loading for Targeted Delivery. Biomacromolecules. 2024 Jan;25(1):155–64.
Deshpande, Sonal, et al. “Enzymatic Synthesis of Aptamer-Polynucleotide Nanoparticles with High Anticancer Drug Loading for Targeted Delivery.Biomacromolecules, vol. 25, no. 1, Jan. 2024, pp. 155–64. Epmc, doi:10.1021/acs.biomac.3c00888.
Deshpande S, Yang Y, Zauscher S, Chilkoti A. Enzymatic Synthesis of Aptamer-Polynucleotide Nanoparticles with High Anticancer Drug Loading for Targeted Delivery. Biomacromolecules. 2024 Jan;25(1):155–164.
Journal cover image

Published In

Biomacromolecules

DOI

EISSN

1526-4602

ISSN

1525-7797

Publication Date

January 2024

Volume

25

Issue

1

Start / End Page

155 / 164

Related Subject Headings

  • Polynucleotides
  • Polymers
  • Nanoparticles
  • Micelles
  • Fluorouracil
  • Drug Delivery Systems
  • Cell Line, Tumor
  • Antineoplastic Agents
  • 40 Engineering
  • 34 Chemical sciences