Targeted delivery of chemotherapeutics to tumors: Design principles, barriers, and future directions

Huarui Zhang; Zhuoheng Pan; Meishen Ren; Yufei Pan; Zefeng Chen; Yihao Zhang; Hang Luo; Xue Xue; Yuan Ma; Junlin He; Wei Kang; Baoting Zhang; Aiping Lu; Sifan Yu; Ge Zhang

doi:10.59717/j.xinn-drugdisc.2026.100036

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Targeted delivery of chemotherapeutics to tumors: Design principles, barriers, and future directions

1.
Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases (TMBJ), School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China
2.
School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR999077, China
3.
Aptacure Therapeutics Limited, Hong Kong SAR 999077, China
4.
Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR 999077, China
5.
Shenzhen Institute for Research and Continuing Education (IRACE), Hong Kong Baptist University, Shenzhen 518057, China
6.
These authors contributed equally to this work

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Corresponding authors: weikang@cuhk.edu.hk (W.K.); zhangbaoting@cuhk.edu.hk (B.Z.); aipinglu@hkbu.edu.hk (A.L.); yusifan@hkbu.edu.hk (S.Y.); zhangge@hkbu.edu.hk (G.Z.)
Received Date: June 09, 2026

Accepted Date: July 31, 2026

Published Online: August 18, 2026

The Innovation Drug Discovery https://doi.org/10.59717/j.xinn-drugdisc.2026.100036 | Cite this article

GRAPHICAL ABSTRACT

GRAPHICAL ABSTRACT

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PUBLIC SUMMARY

PUBLIC SUMMARY
1. Effective targeted delivery requires balancing exposure, penetration, and drug release.
  
  Evaluates major targeting platforms by comparing their size, pharmacokinetics, and drug efficacy.
  
  Programmable aptamer designs enable precise payload loading and controlled release.
  
  Future designs should match delivery platforms to specific tumor barriers using AI.

ABSTRACT

ABSTRACT

Conventional chemotherapy frequently causes uneven drug distribution and systemic toxicity due to inadequate in vivo selectivity. Passive targeting strategies, such as the enhanced permeability and retention effect, can no longer guarantee effective drug accumulation within tumor tissues. The success of active targeted chemotherapy cannot be simplified to a basic “ligand-drug” binding model, but relies on the coordinated regulation of multiple processes, including drug distribution, tumor penetration, cellular internalization, and intracellular processing. From a design-oriented perspective, this review elaborates on the core design logic of targeted chemotherapy delivery and highlights that target expression and accessibility, pharmacokinetic characteristics of targeting moieties, payload compatibility, and drug release mechanisms serve as critical determinants of therapeutic outcomes. Furthermore, this review summarizes and evaluates current mainstream targeted chemotherapy delivery platforms, including antibody-based, aptamer-based, small-molecule, peptide, and hybrid delivery systems. Finally, future research directions for targeted chemotherapy development are prospected. Rather than pursuing a single optimal delivery platform, a problem-oriented design strategy is proposed. The design of next-generation delivery systems requires an optimal balance among targeting construct size, in vivo drug exposure, and tissue permeability, as well as payload release profiles, based on the dominant transport limitations of specific tumor microenvironments.
- Chemotherapy /
- Targeted delivery /
- Target expression /
- Payload /
- Release mechanism

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Zhang H., Pan Z., Ren M., et al. (2026). Targeted delivery of chemotherapeutics to tumors: Design principles, barriers, and future directions. The Innovation Drug Discovery 1:100036. https://doi.org/10.59717/j.xinn-drugdisc.2026.100036

Zhang H., Pan Z., Ren M., et al. (2026). Targeted delivery of chemotherapeutics to tumors: Design principles, barriers, and future directions. The Innovation Drug Discovery 1:100036. https://doi.org/10.59717/j.xinn-drugdisc.2026.100036

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