Investigating the EPR effect of nanomedicines in human renal tumors via ex vivo perfusion strategy

Ding, Yuxun; Xu, Ying-Jin; Yang, Wenzeng; Niu, Pei; Xue, L.; Chen, Yidan; Li, Zhanyong; Liu, Yang; An, Yingli; Liu, Yong; Shen, Wei Feng; Shi, Linqi

doi:10.1016/j.nantod.2020.100970

Cited by 100 publications

(61 citation statements)

References 57 publications

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“…Traditional radioscintigraphy with radioactive 67 Ga, which binds to the plasma protein transferrin (90 kDa), showed selective accumulation of 67 Ga in tumors by virtue of the EPR effect. More recently, intravenously injected nanomedicines demonstrated a tumor-selective EPR effect in breast cancer [17] and renal cancer [18].…”

Section: Issue Concerns Passive Targeting To Tumor Vs the Epr Effectmentioning

confidence: 99%

The 35th Anniversary of the Discovery of EPR Effect: A New Wave of Nanomedicines for Tumor-Targeted Drug Delivery—Personal Remarks and Future Prospects

Maeda

2021

JPM

113

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This Special Issue on the enhanced permeability and retention (EPR) effect commemorates the 35th anniversary of its discovery, the original 1986 Matsumura and Maeda finding being published in Cancer Research as a new concept in cancer chemotherapy. My review here describes the history and heterogeneity of the EPR effect, which involves defective tumor blood vessels and blood flow. We reported that restoring obstructed tumor blood flow overcomes impaired drug delivery, leading to improved EPR effects. I also discuss gaps between small animal cancers used in experimental models and large clinical cancers in humans, which usually involve heterogeneous EPR effects, vascular abnormalities in multiple necrotic foci, and tumor emboli. Here, I emphasize arterial infusion of oily formulations of nanodrugs into tumor-feeding arteries, which is the most tumor-selective drug delivery method, with tumor/blood ratios of 100-fold. This method is literally the most personalized medicine because arterial infusions differ for each patient, and drug doses infused depend on tumor size and anatomy in each patient. Future developments in EPR effect-based treatment will range from chemotherapy to photodynamic therapy, boron neutron capture therapy, and therapies for free radical diseases. This review focuses on our own work, which stimulated numerous scientists to perform research in nanotechnology and drug delivery systems, thereby spawning a new cancer treatment era.

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Section: Issue Concerns Passive Targeting To Tumor Vs the Epr Effectmentioning

confidence: 99%

The 35th Anniversary of the Discovery of EPR Effect: A New Wave of Nanomedicines for Tumor-Targeted Drug Delivery—Personal Remarks and Future Prospects

Maeda

2021

JPM

113

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“…Recently, numerous studies have reported that biodegradable polymeric nanocarriers possess a superior stealth function for the detection of the reticuloendothelial system in the human body and exhibit an enhanced permeability and retention effect [ 56 , 57 , 58 , 59 , 60 , 61 ]. In particular, these polymeric nanoparticles are capable of having several beneficial properties, such as biomimetics, stimuli-sensitivity, easy modification, and exquisite target specificity compared to carriers composed of other materials.…”

Section: Biomedical Applicationsmentioning

confidence: 99%

Stereocomplex Polylactide for Drug Delivery and Biomedical Applications: A Review

Park

et al. 2021

Molecules

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Polylactide (PLA) is among the most common biodegradable polymers, with applications in various fields, such as renewable and biomedical industries. PLA features poly(D-lactic acid) (PDLA) and poly(L-lactic acid) (PLLA) enantiomers, which form stereocomplex crystals through racemic blending. PLA emerged as a promising material owing to its sustainable, eco-friendly, and fully biodegradable properties. Nevertheless, PLA still has a low applicability for drug delivery as a carrier and scaffold. Stereocomplex PLA (sc-PLA) exhibits substantially improved mechanical and physical strength compared to the homopolymer, overcoming these limitations. Recently, numerous studies have reported the use of sc-PLA as a drug carrier through encapsulation of various drugs, proteins, and secondary molecules by various processes including micelle formation, self-assembly, emulsion, and inkjet printing. However, concerns such as low loading capacity, weak stability of hydrophilic contents, and non-sustainable release behavior remain. This review focuses on various strategies to overcome the current challenges of sc-PLA in drug delivery systems and biomedical applications in three critical fields, namely anti-cancer therapy, tissue engineering, and anti-microbial activity. Furthermore, the excellent potential of sc-PLA as a next-generation polymeric material is discussed.

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“…In recent years, Ding et al conducted real-time research on human kidney tumors using X-ray computed tomography to confirm the existence of the EPR effect in humans. The results showed that the significant EPR effect can be found in >87% of human kidney tumors [ 14 ]. However, low-molecular-weight contrast agents do not stay in the tumor and can be washed out in a minute from tumor, which greatly differs from macromolecular drug retention in tumors.…”

Section: Introductionmentioning

confidence: 99%

Nanodrug Delivery Systems Modulate Tumor Vessels to Increase the Enhanced Permeability and Retention Effect

Dong

Sun

Huang

et al. 2021

JPM

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The use of nanomedicine for antitumor therapy has been extensively investigated for a long time. Enhanced permeability and retention (EPR) effect-mediated drug delivery is currently regarded as an effective way to bring drugs to tumors, especially macromolecular drugs and drug-loaded pharmaceutical nanocarriers. However, a disordered vessel network, and occluded or embolized tumor blood vessels seriously limit the EPR effect. To augment the EPR effect and improve curative effects, in this review, we focused on the perspective of tumor blood vessels, and analyzed the relationship among abnormal angiogenesis, abnormal vascular structure, irregular blood flow, extensive permeability of tumor vessels, and the EPR effect. In this commentary, nanoparticles including liposomes, micelles, and polymers extravasate through the tumor vasculature, which are based on modulating tumor vessels, to increase the EPR effect, thereby increasing their therapeutic effect.

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Investigating the EPR effect of nanomedicines in human renal tumors via ex vivo perfusion strategy

Cited by 100 publications

References 57 publications

The 35th Anniversary of the Discovery of EPR Effect: A New Wave of Nanomedicines for Tumor-Targeted Drug Delivery—Personal Remarks and Future Prospects

The 35th Anniversary of the Discovery of EPR Effect: A New Wave of Nanomedicines for Tumor-Targeted Drug Delivery—Personal Remarks and Future Prospects

Stereocomplex Polylactide for Drug Delivery and Biomedical Applications: A Review

Nanodrug Delivery Systems Modulate Tumor Vessels to Increase the Enhanced Permeability and Retention Effect

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