Recent Advances in Smart Linkage Strategies for Developing Drug Conjugates for Targeted Delivery

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Updated: Jun 13, 2025

Synthesis and Bioconjugation of Thiol-Reactive Reagents for the Creation of Site-Selectively Modified Immunoconjugates
08:47

Synthesis and Bioconjugation of Thiol-Reactive Reagents for the Creation of Site-Selectively Modified Immunoconjugates

Published on: March 6, 2019

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Jie Zhang1, Zeyu Yang1, Yu Liu1

  • 1School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, China.

Topics in Current Chemistry (Cham)
|March 13, 2025
PubMed

Insights

Smart linkage technologies enhance targeted drug delivery by creating drug conjugates. These strategies control drug release within tumors, improving cancer treatment efficacy and reducing side effects.

Area of Science:

  • Biomedical Engineering
  • Drug Delivery
  • Oncology

Background:

  • Targeted drug delivery systems aim to improve cancer treatment by minimizing off-target toxicity of chemotherapeutic agents.
  • Drug conjugates, developed using stimulus-responsive linkage technologies, are crucial for controlled drug release at tumor sites.
  • Linker technologies are pivotal in the design, synthesis, and in vivo performance of drug conjugates, directly impacting therapeutic outcomes.

Purpose of the Study:

  • To review smart linkage strategies for designing drug conjugates, focusing on stimuli-responsive drug release.
  • To discuss linker classifications, cleavage mechanisms, modular linkers, and self-assembly in drug conjugates.
  • To address challenges and considerations in the research and clinical application of drug conjugate linkage strategies.

Main Methods:

  • Review of current literature on smart linkage strategies for drug conjugates.
  • Analysis of linker classifications, cleavage mechanisms, and modular designs.
  • Discussion of self-assembly approaches and their applications in drug conjugates.
  • Examination of challenges and enhancement measures for linkage strategies in research and clinical settings.

Main Results:

  • Smart linkers enable controlled release of cytotoxic drugs, influenced by the tumor microenvironment and external stimuli.
  • Modular linkers facilitate efficient conjugate synthesis, while self-assembly offers novel design possibilities.
  • Appropriate linkage strategies can achieve intracellular drug release post-conjugate internalization, maximizing tumor cell killing.

Conclusions:

  • Effective linkage strategies are essential for optimizing drug conjugate design and therapeutic efficacy.
  • Understanding linker mechanisms and stimuli-responsive release is key to advancing targeted cancer therapy.
  • Continued research into linkage strategies, including self-assembly, holds significant promise for future drug conjugate development.
Keywords:
Antibody–drug conjugateControlled drug releaseLinkage strategyPeptide–drug conjugateSelf-assembly

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