Receptor-Mediated Drug Delivery: Redefining Targeted Drug Conjugates in Oncology

Authors

• Keon Niles Jafari, Chapman University
• Charlene Chai, Chapman University
• Shelby Kim, Chapman University
• Kamaljit Kaur, Chapman UniversityFollow

Document Type

Article

Publication Date

3-20-2026

Abstract

Targeted drug delivery (TDD), specifically through targeting ligand–drug conjugates, has reshaped oncology by enabling selective delivery of cytotoxic payloads to cancer cells while minimizing uptake by normal tissues. A key approach relies on exploiting overexpressed cell surface receptors (CSRs) to enable selective uptake of drug conjugates via receptor-mediated endocytosis. This review delineates four clinically validated CSRs (HER2, Trop-2, Nectin-4, and SSTR2) with several FDA-approved drug conjugates. Furthermore, emerging CSRs (EGFR, DLL3, and keratin 1) that may support next-generation TDD platforms for cancer treatment are also highlighted. We discuss how CSR type, density on cancer cells, and its mechanism of endocytosis, as well as the conjugate design for cellular uptake, tissue distribution, ligand size, and linker stability, collectively determine tumor drug accumulation and therapeutic efficacy. From representative examples, we elucidate the rationale for judicious refinement of these parameters, guiding the development of more potent ligands and drug conjugates to enhance the therapeutic efficacy of cytotoxic agents.

Comments

This article was originally published in Pharmaceutics, volume 18, issue 3, in 2026. https://doi.org/10.3390/pharmaceutics18030386

Recommended Citation

Jafari, K.N.; Chai, C.; Kim, S.; Kaur, K. Receptor-Mediated Drug Delivery: Redefining Targeted Drug Conjugates in Oncology. Pharmaceutics 2026, 18, 386. https://doi.org/10.3390/pharmaceutics18030386

Copyright

The authors

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.