Cancer Nanomedicine: Addressing the Dark Side of the Enhanced Permeability and Retention Effect

Huynh, Elizabeth; Zheng, Gang

doi:10.2217/nnm.15.86

Cited by 101 publications

(73 citation statements)

References 15 publications

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“…One possible explanation for the high tumor selectivity of PLP is a combination of two factors. First, the ultra-small size of PLP (<30 nm) might provide an advantage for efficient penetration through the permeable tumor vasculature into the tumor interstitial space, resulting the local enrichment of porphyrins within the tumor (39). Second, porphyrin molecules have their own tumor affinity that could further drive their selective tumor uptake as reported previously (40).…”

Section: Discussionmentioning

confidence: 88%

Multimodal Image-Guided Surgical and Photodynamic Interventions in Head and Neck Cancer: From Primary Tumor to Metastatic Drainage

Muhanna

Cui

Chan

et al. 2016

Clinical Cancer Research

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Purpose: The low survival rate of head and neck cancer (HNC) patients is attributable to late disease diagnosis and high recurrence rate. Current HNC staging has inadequate accuracy and low sensitivity for effective diagnosis and treatment management. The multimodal porphyrin lipoprotein-mimicking nanoparticle (PLP), intrinsically capable of positron emission tomography (PET), fluorescence imaging, and photodynamic therapy (PDT), shows great potential to enhance the accuracy of HNC staging and potentially HNC management.Experimental Design: Using a clinically relevant VX-2 buccal carcinoma rabbit model that is able to consistently develop metastasis to regional lymph nodes after tumor induction, we investigated the abilities of PLP for HNC diagnosis and management.Results: PLPs facilitated accurate detection of primary tumor and metastatic nodes (their PET image signal to surrounding muscle ratios were 10.0 and 7.3, respectively), and provided visualization of the lymphatic drainage from tumor to regional lymph nodes by both preoperative PET and intraoperative fluorescence imaging, allowing the identification of unknown primaries and recurrent tumors. PLP-PDT significantly enhanced cell apoptosis in mouse tumors (73.2% of PLP-PDT group vs 7.1% of PLP alone group) and demonstrated complete eradication of primary tumors and obstruction of tumor metastasis in HNC rabbit model without toxicity in normal tissues or damage to adjacent critical structures.Conclusions: PLPs provide a multimodal imaging and therapy platform that could enhance HNC diagnosis by integrating PET/ computed tomography and fluorescence imaging, and improve HNC therapeutic efficacy and specificity by tailoring treatment via fluorescence-guided surgery and PDT.

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Section: Discussionmentioning

confidence: 88%

Multimodal Image-Guided Surgical and Photodynamic Interventions in Head and Neck Cancer: From Primary Tumor to Metastatic Drainage

Muhanna

Cui

Chan

et al. 2016

Clinical Cancer Research

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“…EPR effect is the increased permeation of blood vessels to tumor interstitial space, surrounding tumor environments. They allow delivery and retention of drugs and imaging agents with moderated specificity [109,110].…”

Section: Iron Oxide Nanoparticles (Ionps)mentioning

confidence: 99%

Molecular Imaging with 68Ga Radio-Nanomaterials: Shedding Light on Nanoparticles

et al. 2018

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Abstract:The combination of radioisotopes and nanomaterials is creating a new library of tracers for molecular imaging, exploiting the sensitivity of nuclear imaging techniques and the size-dependent properties of nanomaterials. This new approach is expanding the range of applications, including the possibility of theranostics. Among the many different combinations, the use of 68 Ga as the radioisotope in the radio-nanomaterial is particularly convenient. The physicochemical properties of this isotope allow incorporating it into many materials with great chemical flexibility. Furthermore, its production from a benchtop generator eases the preparation of the tracer. Here, we review main results from the last years in which a nanomaterial has been radiolabeled with 68 Ga. In thus process, we pay attention to the use of nanomaterials for biomedical imaging in general and main properties of this radioisotope. We study the main methods to carry out such radiolabeling and the most important applications for molecular imaging.

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“…However, some clinical trials have not shown the efficacy of the EPR effect. [28] One possible cause of EPR effect failure could be increased interstitial pressure in the tumor microenvironment. It has also been assumed that the EPR effect cannot be employed after an operation.…”

Section: Nanocariers For Anticancer Drugsmentioning

confidence: 99%

“…Attempts have been made to increase the efficiency of the EPR effect by induction of hypertension, by repairing the abnormal vasculature, or by targeting of perivascular cells. [28] …”

Section: Nanocariers For Anticancer Drugsmentioning

confidence: 99%

Nanocarrier drugs in the treatment of brain tumors

Černá¹,

Stiborová²,

Adam³

et al. 2016

JCMT

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Nanoparticle-mediated targeted delivery of drugs might significantly reduce the dosage and optimize their release properties, increase specificity and bioavailability, improve shelf life, and reduce toxicity. Some nanodrugs are able to overcome the blood-brain barrier that is an obstacle to treatment of brain tumors. Vessels in tumors have abnormal architecture and are highly permeable; moreover, tumors also have poor lymphatic drainage, allowing for accumulation of macromolecules greater than approximately 40 kDa within the tumor microenvironment. Nanoparticles exploit this feature, known as the enhanced permeability and retention effect, to target solid tumors. Active targeting, i.e. surface modification of nanoparticles, is a way to decrease uptake in normal tissue and increase accumulation in a tumor, and it usually involves targeting surface membrane proteins that are upregulated in cancer cells. The targeting molecules are typically antibodies or their fragments; aptamers; oligopeptides or small molecules. There are currently several FDA-approved nanomedicines, but none approved for brain tumor therapy. This review, based both on the study of literature and on the authors own experimental work describes a comprehensive overview of preclinical and clinical research of nanodrugs in therapy of brain tumors. This is an open access article distributed under the terms of the Creative Commons AttributionNonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms. For reprints contact: service@oaepublish.com ReviewOpen Access

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Cancer Nanomedicine: Addressing the Dark Side of the Enhanced Permeability and Retention Effect

Cited by 101 publications

References 15 publications

Multimodal Image-Guided Surgical and Photodynamic Interventions in Head and Neck Cancer: From Primary Tumor to Metastatic Drainage

Multimodal Image-Guided Surgical and Photodynamic Interventions in Head and Neck Cancer: From Primary Tumor to Metastatic Drainage

Molecular Imaging with 68Ga Radio-Nanomaterials: Shedding Light on Nanoparticles

Nanocarrier drugs in the treatment of brain tumors

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