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Bioconjugated Polymer Therapeutics: History
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Contributor: Yu Peng

Bioconjugated polymer therapeutics constitute a class of macromolecular drug delivery systems in which a therapeutic agent—a low-molecular-weight drug, a peptide, a protein, or a nucleic acid—is covalently linked to a water-soluble polymeric carrier through a chemical linker [1][2]. A typical bioconjugate comprises three basic building blocks: the polymeric carrier molecule, the therapeutic agent, and the chemical linker that joins them; because the therapeutic agent is covalently attached rather than physically encapsulated, the resulting construct functions as a macromolecular prodrug [2][3]. The polymeric carrier is selected for biocompatibility, biodegradability, molecular weight, and the availability of functional groups for conjugation, all of which govern drug loading, release kinetics, and biological performance [2][4]. The linker is a defining structural element: it determines whether the therapeutic agent is released by hydrolysis, by enzymatic cleavage, or by a stimulus-responsive trigger such as pH or redox potential, and it thereby controls the site and kinetics of drug liberation [3][5]. Within advanced drug delivery systems, the term designates these covalently assembled polymer–therapeutic conjugates—including polymer–drug conjugates and polymer–protein conjugates—together with the design logic of carrier selection, linker chemistry, and conjugation strategy that determines their pharmacokinetic profile, targeting capacity, and therapeutic index [2][5][6].

  • polymer conjugation
  • macromolecular prodrugs
  • drug loading
  • linker cleavage

Advanced Drug Delivery Systems·Pharmaceutical Science·Pharmacology, Toxicology and Pharmaceutics·Life Sciences

References

  1. Jindřich Kopeček; Jiyuan Yang; Polymer nanomedicines. Adv. Drug Deliv. Rev. 2020, 156, 40-64, 10.1016/j.addr.2020.07.020.
  2. Iriny Ekladious; Yolonda L. Colson; Mark W. Grinstaff; Polymer–drug conjugate therapeutics: advances, insights and prospects. Nat. Rev. Drug Discov. 2018, 18, 273-294, 10.1038/s41573-018-0005-0.
  3. Fatemeh Karimi; Katherine E. S. Locock; John Chiefari; Charlotte C. Williams; Lewis D. Blackman; Challenges and Opportunities for Cleavable Linkers Used in Polymer–Drug Conjugates. J. Am. Chem. Soc. 2026, 148, 20297-20321, 10.1021/jacs.6c03661.
  4. Varaporn Buraphacheep Junyaprasert; Parichart Thummarati; Innovative Design of Targeted Nanoparticles: Polymer–Drug Conjugates for Enhanced Cancer Therapy. Pharmaceutics 2023, 15, 2216, 10.3390/pharmaceutics15092216.
  5. Vinay Sagar Verma; Aakansha Pandey; Arvind Kumar Jha; Hemant Kumar Ramchandra Badwaik; Amit Alexander; Ajazuddin; Polyethylene Glycol–Based Polymer-Drug Conjugates: Novel Design and Synthesis Strategies for Enhanced Therapeutic Efficacy and Targeted Drug Delivery. Appl. Biochem. Biotechnol. 2024, 196, 7325-7361, 10.1007/s12010-024-04895-6.
  6. Douglas A. Rose; Zihuan Fu; Mikayla F. Tan; Daniele Vinciguerra; Priera H. Panescu; Heather D. Maynard; Traceless linkers used for reversible protein–polymer conjugations. Chem. Sci. 2026, 17, 3410-3429, 10.1039/d5sc05801e.
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