Strategies to enhance drug delivery to solid tumors by harnessing the EPR effects and alternative targeting mechanisms

[Display omitted] The Enhanced Permeability and Retention (EPR) effect has been recognized as the central paradigm in tumor-targeted delivery in the last decades. In the wake of this concept, nanotechnologies have reached phenomenal levels in research. However, clinical tumors display a poor manifes...

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Vydané v:Advanced drug delivery reviews Ročník 188; s. 114449
Hlavní autori: Zi, Yixuan, Yang, Kaiyun, He, Jianhua, Wu, Zimei, Liu, Jianping, Zhang, Wenli
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: Netherlands Elsevier B.V 01.09.2022
Predmet:
Antineoplastic Agents
Clinical translation
Drug Delivery Systems - methods
EPR effect
Humans
independent of EPR effect
Nanomedicine
Nanomedicine - methods
Nanoparticles
Neoplasms - therapy
Permeability
Preclinical models
Transendothelial pathway
Tumor Microenvironment
Clinical translation
Transendothelial pathway
independent of EPR effect
Nanomedicine
Preclinical models
EPR effect
ISSN:0169-409X, 1872-8294, 1872-8294
On-line prístup:Získať plný text
Tagy: Pridať tag
Žiadne tagy, Buďte prvý, kto otaguje tento záznam!
Abstract [Display omitted] The Enhanced Permeability and Retention (EPR) effect has been recognized as the central paradigm in tumor-targeted delivery in the last decades. In the wake of this concept, nanotechnologies have reached phenomenal levels in research. However, clinical tumors display a poor manifestation of EPR effect. Factors including tumor heterogeneity, complicating tumor microenvironment, and discrepancies between laboratory models and human tumors largely contribute to poor efficiency in tumor-targeted delivery and therapeutic failure in clinical translation. In this article, approaches for evaluation of EPR effect in human tumor were overviewed as guidance to employ EPR effect for cancer treatment. Strategies to augment EPR-mediated tumoral delivery are discussed in different dimensions including enhancement of vascular permeability, depletion of tumor extracellular matrix and optimization of nanoparticle design. Besides, the recent development in alternative tumor-targeted delivery mechanisms are highlighted including transendothelial pathway, endogenous cell carriers and non-immunogenic bacteria-mediated delivery. In addition, the emerging preclinical models better reflect human tumors are introduced. Finally, more rational applications of EPR effect in other disease and field are proposed. This article elaborates on fundamental reasons for the gaps between theoretical expectation and clinical outcomes, attempting to provide some perspective directions for future development of cancer nanomedicines in this still evolving landscape.
AbstractList The Enhanced Permeability and Retention (EPR) effect has been recognized as the central paradigm in tumor-targeted delivery in the last decades. In the wake of this concept, nanotechnologies have reached phenomenal levels in research. However, clinical tumors display a poor manifestation of EPR effect. Factors including tumor heterogeneity, complicating tumor microenvironment, and discrepancies between laboratory models and human tumors largely contribute to poor efficiency in tumor-targeted delivery and therapeutic failure in clinical translation. In this article, approaches for evaluation of EPR effect in human tumor were overviewed as guidance to employ EPR effect for cancer treatment. Strategies to augment EPR-mediated tumoral delivery are discussed in different dimensions including enhancement of vascular permeability, depletion of tumor extracellular matrix and optimization of nanoparticle design. Besides, the recent development in alternative tumor-targeted delivery mechanisms are highlighted including transendothelial pathway, endogenous cell carriers and non-immunogenic bacteria-mediated delivery. In addition, the emerging preclinical models better reflect human tumors are introduced. Finally, more rational applications of EPR effect in other disease and field are proposed. This article elaborates on fundamental reasons for the gaps between theoretical expectation and clinical outcomes, attempting to provide some perspective directions for future development of cancer nanomedicines in this still evolving landscape.
[Display omitted] The Enhanced Permeability and Retention (EPR) effect has been recognized as the central paradigm in tumor-targeted delivery in the last decades. In the wake of this concept, nanotechnologies have reached phenomenal levels in research. However, clinical tumors display a poor manifestation of EPR effect. Factors including tumor heterogeneity, complicating tumor microenvironment, and discrepancies between laboratory models and human tumors largely contribute to poor efficiency in tumor-targeted delivery and therapeutic failure in clinical translation. In this article, approaches for evaluation of EPR effect in human tumor were overviewed as guidance to employ EPR effect for cancer treatment. Strategies to augment EPR-mediated tumoral delivery are discussed in different dimensions including enhancement of vascular permeability, depletion of tumor extracellular matrix and optimization of nanoparticle design. Besides, the recent development in alternative tumor-targeted delivery mechanisms are highlighted including transendothelial pathway, endogenous cell carriers and non-immunogenic bacteria-mediated delivery. In addition, the emerging preclinical models better reflect human tumors are introduced. Finally, more rational applications of EPR effect in other disease and field are proposed. This article elaborates on fundamental reasons for the gaps between theoretical expectation and clinical outcomes, attempting to provide some perspective directions for future development of cancer nanomedicines in this still evolving landscape.
The Enhanced Permeability and Retention (EPR) effect has been recognized as the central paradigm in tumor-targeted delivery in the last decades. In the wake of this concept, nanotechnologies have reached phenomenal levels in research. However, clinical tumors display a poor manifestation of EPR effect. Factors including tumor heterogeneity, complicating tumor microenvironment, and discrepancies between laboratory models and human tumors largely contribute to poor efficiency in tumor-targeted delivery and therapeutic failure in clinical translation. In this article, approaches for evaluation of EPR effect in human tumor were overviewed as guidance to employ EPR effect for cancer treatment. Strategies to augment EPR-mediated tumoral delivery are discussed in different dimensions including enhancement of vascular permeability, depletion of tumor extracellular matrix and optimization of nanoparticle design. Besides, the recent development in alternative tumor-targeted delivery mechanisms are highlighted including transendothelial pathway, endogenous cell carriers and non-immunogenic bacteria-mediated delivery. In addition, the emerging preclinical models better reflect human tumors are introduced. Finally, more rational applications of EPR effect in other disease and field are proposed. This article elaborates on fundamental reasons for the gaps between theoretical expectation and clinical outcomes, attempting to provide some perspective directions for future development of cancer nanomedicines in this still evolving landscape.The Enhanced Permeability and Retention (EPR) effect has been recognized as the central paradigm in tumor-targeted delivery in the last decades. In the wake of this concept, nanotechnologies have reached phenomenal levels in research. However, clinical tumors display a poor manifestation of EPR effect. Factors including tumor heterogeneity, complicating tumor microenvironment, and discrepancies between laboratory models and human tumors largely contribute to poor efficiency in tumor-targeted delivery and therapeutic failure in clinical translation. In this article, approaches for evaluation of EPR effect in human tumor were overviewed as guidance to employ EPR effect for cancer treatment. Strategies to augment EPR-mediated tumoral delivery are discussed in different dimensions including enhancement of vascular permeability, depletion of tumor extracellular matrix and optimization of nanoparticle design. Besides, the recent development in alternative tumor-targeted delivery mechanisms are highlighted including transendothelial pathway, endogenous cell carriers and non-immunogenic bacteria-mediated delivery. In addition, the emerging preclinical models better reflect human tumors are introduced. Finally, more rational applications of EPR effect in other disease and field are proposed. This article elaborates on fundamental reasons for the gaps between theoretical expectation and clinical outcomes, attempting to provide some perspective directions for future development of cancer nanomedicines in this still evolving landscape.
ArticleNumber 114449
Author Zi, Yixuan
Liu, Jianping
Yang, Kaiyun
Zhang, Wenli
He, Jianhua
Wu, Zimei
Author_xml – sequence: 1
  givenname: Yixuan
  surname: Zi
  fullname: Zi, Yixuan
  organization: Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, PR China
– sequence: 2
  givenname: Kaiyun
  surname: Yang
  fullname: Yang, Kaiyun
  organization: School of Pharmacy, University of Auckland, Private Bag 92019, Auckland, New Zealand
– sequence: 3
  givenname: Jianhua
  surname: He
  fullname: He, Jianhua
  organization: Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, PR China
– sequence: 4
  givenname: Zimei
  surname: Wu
  fullname: Wu, Zimei
  email: z.wu@auckland.ac.nz
  organization: School of Pharmacy, University of Auckland, Private Bag 92019, Auckland, New Zealand
– sequence: 5
  givenname: Jianping
  surname: Liu
  fullname: Liu, Jianping
  email: jianping1293@163.com
  organization: Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, PR China
– sequence: 6
  givenname: Wenli
  surname: Zhang
  fullname: Zhang, Wenli
  email: zwllz@163.com
  organization: Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, PR China
BackLink https://www.ncbi.nlm.nih.gov/pubmed/35835353$$D View this record in MEDLINE/PubMed
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Keywords Clinical translation
Transendothelial pathway
independent of EPR effect
Nanomedicine
Preclinical models
EPR effect
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Snippet [Display omitted] The Enhanced Permeability and Retention (EPR) effect has been recognized as the central paradigm in tumor-targeted delivery in the last...
The Enhanced Permeability and Retention (EPR) effect has been recognized as the central paradigm in tumor-targeted delivery in the last decades. In the wake of...
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SubjectTerms Antineoplastic Agents
Clinical translation
Drug Delivery Systems - methods
EPR effect
Humans
independent of EPR effect
Nanomedicine
Nanomedicine - methods
Nanoparticles
Neoplasms - therapy
Permeability
Preclinical models
Transendothelial pathway
Tumor Microenvironment
Title Strategies to enhance drug delivery to solid tumors by harnessing the EPR effects and alternative targeting mechanisms
URI https://dx.doi.org/10.1016/j.addr.2022.114449
https://www.ncbi.nlm.nih.gov/pubmed/35835353
https://www.proquest.com/docview/2691053986
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