The EPR effect: Unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect

Fang, Jun; Nakamura, Hideaki; Maeda, Hiroshi

doi:10.1016/j.addr.2010.04.009

Cited by 3,125 publications

(2,250 citation statements)

References 105 publications

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“…Nanomedicines can exploit defects in tumor microvasculature which allow for preferential tumoral accumulation based on the so‐called enhanced permeability and retention (EPR) effect 12, 13, 14. However, the EPR effect alone is generally an insufficient mechanism, as there are additional barriers such as high interstitial fluid pressure15 and heterogeneous tumor vasculature 16.…”

Section: Introductionmentioning

confidence: 99%

Chemophototherapy: An Emerging Treatment Option for Solid Tumors

et al. 2016

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Near infrared (NIR) light penetrates human tissues with limited depth, thereby providing a method to safely deliver non‐ionizing radiation to well‐defined target tissue volumes. Light‐based therapies including photodynamic therapy (PDT) and laser‐induced thermal therapy have been validated clinically for curative and palliative treatment of solid tumors. However, these monotherapies can suffer from incomplete tumor killing and have not displaced existing ablative modalities. The combination of phototherapy and chemotherapy (chemophototherapy, CPT), when carefully planned, has been shown to be an effective tumor treatment option preclinically and clinically. Chemotherapy can enhance the efficacy of PDT by targeting surviving cancer cells or by inhibiting regrowth of damaged tumor blood vessels. Alternatively, PDT‐mediated vascular permeabilization has been shown to enhance the deposition of nanoparticulate drugs into tumors for enhanced accumulation and efficacy. Integrated nanoparticles have been reported that combine photosensitizers and drugs into a single agent. More recently, light‐activated nanoparticles have been developed that release their payload in response to light irradiation to achieve improved drug bioavailability with superior efficacy. CPT can potently eradicate tumors with precise spatial control, and further clinical testing is warranted.

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Section: Introductionmentioning

confidence: 99%

Chemophototherapy: An Emerging Treatment Option for Solid Tumors

et al. 2016

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“…These characters are known as the enhanced permeability and retention (EPR) effects that have been widely used to enhance the tumor selectivity of antitumor nanomedicines [6][7][8]. It was reported that with time the concentration of some intravenously (IV) administered nanosized anticancer drugs at the tumors could become several folds higher than that in normal tissues [9,10]. Naturally, the central focus of current studies has been on how to increase the retention and accumulation of nanoparticles in tumor vasculatures for better tumor targeting therapy and imaging [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

A highly efficient and tumor vascular-targeting therapeutic technique with size-expansible gadofullerene nanocrystals

Zhen

Shu

et al. 2015

Sci. China Mater.

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It has long been a dream to achieve tumor targeting therapy that can efficiently reduce the toxicity and severe side effects of conventional antitumor chemotherapeutic agents. Taking advantage of the abnormalities of tumor vasculature, we demonstrate here a new powerful tumor vascular-targeting therapeutic technique for solid cancers that applies advanced nanotechnology to cut off the nutrient supply of tumor cells by physically destroying the abnormal tumor blood vessels. Water soluble magnetic Gd@C82 nanocrystals of the chosen sizes are deliberately designed with abilities to penetrate into the leaky tumor blood vessels. By triggering the radiofrequency induced phase transition of gadofullerene nanocrystals while extravasating the tumor blood vessel, the explosive structural change of nanoparticles generates a devastating impact on abnormal tumor blood vessels, resulting in a rapid and extensive ischemia necrosis and shrinkage of the tumors. This unprecedented target-specific physiotherapy is found to work perfectly for advanced and refractory solid tumors.

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“…This means that some portions of the tumor cells will reach an appropriate temperature to induce apoptosis and some will not. This is particularly true for tumors peripheral to large blood vessels which facilitate rapid dissipation of heat through the circulation of blood [206,225,226]. In order to improve efficiency, many researchers have combined PTA with drug delivery to enhance the destruction of cancer cells during treatment.…”

Section: Multi-modal Treatmentsmentioning

confidence: 99%

Controllable Cobalt Oxide/Au Hierarchically Nanostructured Electrode for Nonenzymatic Glucose Sensing

2016

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By electrodeposition and galvanic replacement reaction, we developed a facile, time-saving, cost-effective, and environmentally friendly, two-step synthesis route to obtain a controllable cobalt oxide/Au hierarchically nanostructured electrode for glucose sensing. The nanomaterials were characterized by transmission electron microscopy, scanning electron microscopy, Raman spectroscopy, energy-dispersive spectrometry, and X-ray photoelectron spectroscopy, meanwhile, the sensing performance was investigated by cyclic voltammetry and amperometric response. The results revealed that this novel electrode exhibited excellent electrocatalytic performance toward glucose oxidation, with a wide double-linear range from 0.2 μM to 20 mM and a low detection limit of 0.1 μM based on a signal-to-noise ratio of 3, which was mainly attributed to the ability of loading a small amount of Au with good electron conductivity on the surface of cobalt oxide nanosheets with large active surface area and synergistic electrocatalytic activity of Au and cobalt oxide toward glucose electrooxidation. This facile, sensitive, and selective glucose sensor is also proven to be suitable for the detection of glucose in human serum.

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The EPR effect: Unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect

Cited by 3,125 publications

References 105 publications

Chemophototherapy: An Emerging Treatment Option for Solid Tumors

Chemophototherapy: An Emerging Treatment Option for Solid Tumors

A highly efficient and tumor vascular-targeting therapeutic technique with size-expansible gadofullerene nanocrystals

Controllable Cobalt Oxide/Au Hierarchically Nanostructured Electrode for Nonenzymatic Glucose Sensing

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