Targeting integrins and enhanced permeability and retention (EPR) effect for optical imaging of oral cancer

2011 ◽  
Vol 105 (7) ◽  
pp. 714-718 ◽  
Author(s):  
Stijn Keereweer ◽  
Isabel M. Mol ◽  
Jeroen D.F. Kerrebijn ◽  
Pieter B.A.A. Van Driel ◽  
Bangwen Xie ◽  
...  
Keyword(s):  
Oral Cancer ◽  
Optical Imaging ◽  
Epr Effect ◽  
Enhanced Permeability And Retention

O125. Targeting integrins and enhanced permeability and retention (EPR) effect for optical imaging of oral cancer

Oral Oncology ◽  
2011 ◽  
Vol 47 ◽  
pp. S70-S71 ◽  
Author(s):  
S. Keereweer ◽  
I.M. Mol ◽  
J.D.F. Kerrebijn ◽  
A.L. Vahrmeijer ◽  
R.J. Baatenburg de Jong ◽  
...  
Keyword(s):  
Oral Cancer ◽  
Optical Imaging ◽  
Epr Effect ◽  
Enhanced Permeability And Retention

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

2021 ◽  
Vol 11 (2) ◽  
pp. 124
Author(s):  
Dong Huang ◽  
Lingna Sun ◽  
Leaf Huang ◽  
Yanzuo Chen
Keyword(s):  
Blood Vessels ◽  
Tumor Vessels ◽  
Epr Effect ◽  
Nanodrug Delivery ◽  
Enhanced Permeability And Retention ◽  
Macromolecular Drugs ◽  
Long Time ◽  
Vessel Network ◽  
Tumor Blood Vessels ◽  
The Relationship

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.

scholarly journals Thirty Years of Cancer Nanomedicine: Success, Frustration, and Hope

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1855 ◽  
Author(s):  
Lucia Salvioni ◽  
Maria Antonietta Rizzuto ◽  
Jessica Armida Bertolini ◽  
Laura Pandolfi ◽  
Miriam Colombo ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Safety Profile ◽  
Crucial Role ◽  
Clinical Relevance ◽  
Scientific Community ◽  
Design Development ◽  
Manufacturing Costs ◽  
Epr Effect ◽  
Enhanced Permeability And Retention ◽  
Cancer Nanomedicine

Starting with the enhanced permeability and retention (EPR) effect discovery, nanomedicine has gained a crucial role in cancer treatment. The advances in the field have led to the approval of nanodrugs with improved safety profile and still inspire the ongoing investigations. However, several restrictions, such as high manufacturing costs, technical challenges, and effectiveness below expectations, raised skeptical opinions within the scientific community about the clinical relevance of nanomedicine. In this review, we aim to give an overall vision of the current hurdles encountered by nanotherapeutics along with their design, development, and translation, and we offer a prospective view on possible strategies to overcome such limitations.

scholarly journals Enhanced nanodrug delivery in tumors after near-infrared photoimmunotherapy

Nanophotonics ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1673-1688 ◽  
Author(s):  
Fuyuki F. Inagaki ◽  
Aki Furusawa ◽  
Peter L. Choyke ◽  
Hisataka Kobayashi
Keyword(s):  
Near Infrared ◽  
Small Molecular Weight ◽  
Small Magnitude ◽  
Epr Effect ◽  
Nanodrug Delivery ◽  
Enhanced Permeability And Retention ◽  
Naturally Occurring ◽  
Limited Success ◽  
Effective Manner ◽  
Promising Avenue

AbstractTo date, the delivery of nanosized therapeutic agents to cancers largely relies on the enhanced permeability and retention (EPR) effects that are caused by the leaky nature of cancer vasculature. Whereas leaky vessels are often found in mouse xenografts, nanosized agents have demonstrated limited success in humans due to the relatively small magnitude of the EPR effect in naturally occurring cancers. To achieve the superior delivery of nanosized agents, alternate methods of increasing permeability and retention are needed. Near-infrared photoimmunotherapy (NIR-PIT) is a recently reported therapy that relies on an antibody-photon absorber conjugate that binds to tumors and then is activated by light. NIR-PIT causes an increase in nanodrug delivery by up to 24-fold compared to untreated tumors in which only the EPR effect is present. This effect, termed super-EPR (SUPR), can enhance the delivery of a wide variety of nanosized agents, including nanoparticles, antibodies, and protein-binding small-molecular-weight agents into tumors. Therefore, taking advantage of the SUPR effect after NIR-PIT may be a promising avenue to use a wide variety of nanodrugs in a highly effective manner.

scholarly journals Detection and delineation of oral cancer with a PARP1 targeted optical imaging agent

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Susanne Kossatz ◽  
Christian Brand ◽  
Stanley Gutiontov ◽  
Jonathan T. C. Liu ◽  
Nancy Y. Lee ◽  
...  
Keyword(s):  
Oral Cancer ◽  
Optical Imaging ◽  
Imaging Agent

From Passive Targeting to Personalized Nanomedicine: Multidimensional Insights on Nanoparticles’ Interaction with the Tumor Microenvironment

2020 ◽  
Vol 21 ◽  
Author(s):  
Aya A. Sebak ◽  
Basma M. El-Shenawy ◽  
Sara El-Safy ◽  
Mohamed El-Shazly
Keyword(s):  
Tumor Microenvironment ◽  
Protein Corona ◽  
Lymphatic Drainage ◽  
Biological Macromolecules ◽  
Passive Targeting ◽  
Epr Effect ◽  
The Past ◽  
Current Trends ◽  
Enhanced Permeability And Retention ◽  
Therapeutic Outcomes

: Nanomedicine is revolutionizing the treatment of cancer and has achieved unprecedented outcomes over the past decades. The accumulation of nanoparticles (NPs) in different tumors relies mainly on the enhanced permeability and retention (EPR) effect benefiting from the wide fenestrae of the tumor vasculature and the lack of lymphatic drainage. However, the EPR effect is recognized as a heterogeneous phenomenon resulting in heterogeneous outcomes of clinical trials. Extensive efforts are exerted to enhance the outcomes of nanomedicine in a larger cohort of patients by employing active targeting strategies. However, actively targeted NPs accumulate in tumors by the EPR effect and hence fail to achieve convincing therapeutic outcomes. These obstacles are gradually being removed by improving the understanding of the tumor microenvironment (TME) and the mechanistic interaction of the NPs with its different components. In this review, we provide detailed insights into the past concerns of drug targeting, the current trends of TME reengineering, and the future implications for overcoming past hurdles. Strategies explored in this regard included the use of companion diagnostics and the modulation of the protein corona associated with the systemic administration of NPs and their interaction with biological macromolecules.

scholarly journals Impact of the Enhanced Permeability and Retention (EPR) Effect and Cathepsins Levels on the Activity of Polymer-Drug Conjugates

Polymers ◽  
2014 ◽  
Vol 6 (8) ◽  
pp. 2186-2220 ◽  
Author(s):  
Amit Rajora ◽  
Divyashree Ravishankar ◽  
Helen Osborn ◽  
Francesca Greco
Keyword(s):  
Epr Effect ◽  
Drug Conjugates ◽  
Enhanced Permeability And Retention ◽  
Polymer Drug Conjugates

scholarly journals PARP1 as a biomarker for early detection and intraoperative tumor delineation in epithelial cancers – first-in-human results

2019 ◽  
Author(s):  
Susanne Kossatz ◽  
Giacomo Pirovano ◽  
Paula Demétrio De Souza França ◽  
Arianna L. Strome ◽  
Sumsum P. Sunny ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Oral Cancer ◽  
Early Detection ◽  
Optical Imaging ◽  
Surgical Margin ◽  
Surrounding Tissue ◽  
Imaging Biomarker ◽  
Visual Aids ◽  
Clinical Value ◽  
Epithelial Surface

AbstractMajor determining factors for survival of patients with oral, oropharyngeal, and esophageal cancer are early detection, the quality of surgical margins, and the contemporaneous detection of residual tumor. Intuitively, the exposed location at the epithelial surface qualifies these tumor types for utilization of visual aids to assist in discriminating tumor from healthy surrounding tissue. Here, we explored the DNA repair enzyme PARP1 as imaging biomarker and conducted optical imaging in animal models, human tissues and as part of a first-in-human clinical trial. Our data suggests that PARP1 is a quantitative biomarker for oral, oropharyngeal, and esophageal cancer and can be visualized with PARPi-FL, a fluorescently labeled small molecule contrast agent for topical or intravenous delivery. We show feasibility of PARPi-FL-assisted tumor detection in esophageal cancer, oropharyngeal and oral cancer. We developed a contemporaneous PARPi-FL topical staining protocol for human biospecimens. Using fresh oral cancer tissues within 25 min of biopsy, tumor and margin samples were correctly identified with >95% sensitivity and specificity without terminal processing. PARPi-FL imaging can be integrated into clinical workflows, potentially providing instantaneous assessment of the presence or absence of microscopic disease at the surgical margin. Additionally, we showed first-in-human PARPi-FL imaging in oral cancer. In aggregate, our preclinical and clinical studies have the unifying goal of verifying the clinical value of PARPi-FL-based optical imaging for early detection and intraoperative margin assignment.

Σύνθεση, χαρακτηρισμός και βιολογική αξιολόγηση νανοδομών επισημασμένων με ραδιοϊσότοπα εκπομπής γ-φωτονίων και ποζιτρονίων

2021 ◽  
Author(s):  
Θεοδώρα Κούτσικου
Keyword(s):  
Epr Effect ◽  
Enhanced Permeability And Retention

Tην τελευταία δεκαετία, η πρόοδος στον σχεδιασμό ελεγχόμενων συστημάτων μεταφοράς φαρμάκων οδήγησε σε τεράστια ανάπτυξη στη θεραπεία πολλών ασθενειών. Στη μελέτη αυτή ένα είδος σύνθετου νανο-φορέα πυρήνα-κελύφους με μια εσωτερική κοιλότητα σχηματίστηκε με πολυμερισμό γαλακτώματος από μια ποικιλία μονομερών με ειδικές ευαισθησίες. Το μικρό μέγεθος αυτής της δομής επιτρέπει στους νανοφορείς να διαπεράσουν διάφορους βιολογικούς φραγμούς και να επιτύχουν παθητική στόχευση μέσω της επίδρασης ενισχυμένης διαπερατότητας και κατακράτησης (Enhanced Permeability and Retention Effect, EPR effect), η οποία διευκολύνει την απελευθέρωση φαρμάκων ιδιαίτερα στους επιθυμητούς ιστούς χωρίς να προκαλούνται δυσμενείς αντιδράσεις στη θεραπεία των ασθενειών όπως για παράδειγμα στη θεραπεία του καρκίνου. Η συνθετική πορεία αποτελείται από δύο στάδια. Στο πρώτο στάδιο συντίθεται ένας μη τοξικός σφαιρικός πυρήνας και στο δεύτερο στάδιο το κέλυφος σχηματίζεται από ένα συνδυασμό μονομερών. Κάθε μονομερές παρουσιάζει μία μοναδική ευαισθησία όπως pΗ, θερμοκρασιακή και ευαισθησία στο οξειδοαναγωγικό περιβάλλον. Αξιοποιώντας αυτή τη συμπεριφορά και απομακρύνοντας τον πυρήνα, συντέθηκαν νανοδοχεία (NCs) ικανά να ανταποκριθούν σε εξωτερικό ερέθισμα που προκαλεί απελευθέρωση φαρμάκου με ελεγχόμενο τρόπο. Το κύριο πλεονέκτημα αυτής της εργασίας, όσον αφορά τη συνθετική διαδικασία, είναι το εσωτερικό των σφαιρών που διαμορφώθηκε κατά τη διάρκεια του σχηματισμού του κελύφους, επιτρέποντας στα μικρά μόρια, βιολογικού ενδιαφέροντος (αναστολείς), να φιλοξενηθούν και παράλληλα να αποδεσμευτούν στην περιοχή του όγκου. Συμπερασματικά, στην εργασία αυτή, παρουσιάζεται η σύνθεση, ο χαρακτηρισμός αλλά και η βιολογική αξιολόγηση κοίλων νανοδοχείων (ΝCs), με διαφορετικές ευαισθησίες, ως εν δυνάμει συστημάτων μεταφοράς φαρμάκων για τη θεραπεία του καρκίνου ιχνηθετημένα με ραδιενεργά ισότοπα, όπως για παράδειγμα 68Ga και 99mTc.

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