The tumor EPR effect for cancer drug delivery: Current status, limitations, and alternatives

Rui Sun; Jiajia Xiang; Quan Zhou; Ying Piao; Jianbin Tang; Shiqun Shao; Zhuxian Zhou; You Han Bae; Youqing Shen

doi:10.1016/j.addr.2022.114614

The tumor EPR effect for cancer drug delivery: Current status, limitations, and alternatives

Adv Drug Deliv Rev. 2022 Dec:191:114614. doi: 10.1016/j.addr.2022.114614. Epub 2022 Nov 5.

Authors

Rui Sun¹, Jiajia Xiang², Quan Zhou³, Ying Piao¹, Jianbin Tang², Shiqun Shao², Zhuxian Zhou⁴, You Han Bae⁵, Youqing Shen⁶

Affiliations

¹ Zhejiang Key Laboratory of Smart Biomaterials and Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China.
² Zhejiang Key Laboratory of Smart Biomaterials and Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China; ZJU-Hangzhou Global Scientific and Technological Innovation Center, Hangzhou 311215, China.
³ Zhejiang Key Laboratory of Smart Biomaterials and Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China; Department of Cell Biology, School of Basic Medical Sciences, Zhejiang University, Hangzhou 310058, China.
⁴ Zhejiang Key Laboratory of Smart Biomaterials and Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China. Electronic address: zhouzx@zju.edu.cn.
⁵ Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA. Electronic address: you.bae@utah.edu.
⁶ Zhejiang Key Laboratory of Smart Biomaterials and Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China. Electronic address: shenyq@zju.edu.cn.

PMID: 36347432
DOI: 10.1016/j.addr.2022.114614

Abstract

Over the past three decades, the enhanced permeability and retention (EPR) effect has been considered the basis of tumor-targeted drug delivery. Various cancer nanomedicines, including macromolecular drugs, have been designed to utilize this mechanism for preferential extravasation and accumulation in solid tumors. However, such nanomedicines have not yet achieved convincing therapeutic benefits in clinics. Increasing evidence suggests that the EPR effect is over-represented in human tumors, especially in metastatic tumors. This review covers the evolution of the concept, the heterogeneity and limitation of the EPR effect in clinical realities, and prospects for alternative strategies independent of the EPR effect.

Keywords: Cancer drug delivery; EPR effect; EPR effect alternatives; EPR effect augmentation; Heterogenicity.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents* / therapeutic use
Drug Delivery Systems
Humans
Nanomedicine
Neoplasms* / therapy
Permeability

Substances

Antineoplastic Agents