Challenges and key considerations of the enhanced permeability and retention (EPR) effect for nanomedicine drug delivery in oncology

By U. Prabhakar, H. Maeda, Rakesh K. Jain, Eva M. Sevick-Muraca, W. Zamboni, O. Farokhzad, S. Barry, A. Gabizon, Piotr Grodzinski, D. Blakey. Cancer Research, 2013

1,264 citations recorded by the source corpus.

Enhanced permeability of the tumor vasculature allows macromolecules to enter the tumor interstitial space, while the suppressed lymphatic filtration allows them to stay there. This phenomenon - EPR has been the basis of nanotechnology platforms to deliver drugs to tumors. However, progress in developing effective drugs using this approach has been hampered by heterogeneity of EPR effect in different tumors and limited experimental data from patients on effectiveness of this mechanism as related to enhanced drug accumulation. This report summarizes the workshop discussions on key issues of the EPR effect and major gaps that need to be addressed to effectively advance nanoparticle-based drug delivery.

Subfields: Biomaterials, Biomedical Engineering, Electronic, Optical and Magnetic Materials

View Paper: https://www.semanticscholar.org/paper/b986a241eb37ee987619362d5e2bd2f9522d48e9

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Biomaterials

1. N. Bertrand
2. N. Kamaly
3. Xiaoyang Xu
4. Jun Wu
5. O. Farokhzad
6. E. Holler
7. R. Juliano
8. E. S. Day

In Biomedical Engineering

1. N. Bertrand
2. Xiaoyang Xu
3. N. Kamaly
4. Jun Wu
5. O. Farokhzad
6. W. Choi
7. S. Barry
8. Basit Yameen

In Electronic, Optical and Magnetic Materials

1. O. Farokhzad
2. N. Bertrand
3. E. S. Day
4. Rachel S. Riley

Citations in the corpus

• Nanomedicine therapeutic approaches to overcome cancer drug resistance (2013, background): “Currently, the available clinical data relate to passively targeted liposomes, but a number of actively targeting nanoparticles are also in clinical development [79].”
• Engineering the Delivery System for CRISPR-based Genome Editing (2018, background): “These can range from passive size-based approaches which leverage native uptake and clearance mechanisms [60] or the tumor-specific EPR effects [61], to the inclusion of a wide range of active targeting ligands to direct drug delivery to a particular organ [62, 63].”
• Cancer nanotechnology: the impact of passive and active targeting in the era of modern cancer biology. (2014, background): “The affinity of these macrophages for the colloid and the resulting phagocytic activity can further impede the NPs movement toward the cancer cells while increasing their retention in the tumor interstitium [27].”
• The delivery of therapeutic oligonucleotides (2016, background): “While this is clearly true for a number of rapidly growing xenograft tumors, not all xenografts display a strong EPR effect, and the extent of the effect in human tumors is rather unclear (52,53).”
• Factors controlling the pharmacokinetics, biodistribution and intratumoral penetration of nanoparticles. (2013, background): “It is becoming widely accepted that only a selected population of patients with highly permeable tumors can benefit from nanomedicine [74-76], and a selection tool is needed to identify the receptive population.”
• Clinical translation of an ultrasmall inorganic optical-PET imaging nanoparticle probe (2014, background): “No notable accumulation was observed in the RES, in contrast to many hydrophobic molecules, proteins, and larger-particle (>10 nm) platforms (10).”
• Gold nanoparticle-mediated photothermal therapy: applications and opportunities for multimodal cancer treatment (2017, background): “This is particularly important given that the EPR effect is now known to be heterogeneous in distinct tumor types.(27) Intriguingly, PTT can be used to overcome these tumor penetration and retention limitations by amplifying tumor vessel leakiness and extracellular matrix permeability to enhance the”
• Insight into nanoparticle cellular uptake and intracellular targeting (2014, positive): “The groundbreaking discovery of the EPR effect [13,14] associated with the tumor because of the abnormal and leaky microvasculature has emerged as the foundation for the passively targeted first generation of nanomedicines preferentially accumulating in tumor tissue [15, 16].”