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.

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.

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.

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 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

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

scholarly journals The Enhanced Permeability and Retention (EPR) Effect: The Significance of the Concept and Methods to Enhance Its Application

2021 ◽  
Vol 11 (8) ◽  
pp. 771
Author(s):  
Jun Wu
Keyword(s):  
Clinical Practice ◽  
Solid Tumor ◽  
Tumor Tissue ◽  
Fundamental Problem ◽  
Anticancer Compounds ◽  
Epr Effect ◽  
Enhanced Permeability And Retention ◽  
Satisfactory Outcome ◽  
Targeting Delivery ◽  
Solid Tumor Tissue

Chemotherapy for human solid tumors in clinical practice is far from satisfactory. Despite the discovery and synthesis of hundreds of thousands of anticancer compounds targeting various crucial units in cancer cell proliferation and metabolism, the fundamental problem is the lack of targeting delivery of these compounds selectively into solid tumor tissue to maintain an effective concentration level for a certain length of time for drug-tumor interaction to execute anticancer activities. The enhanced permeability and retention effect (EPR effect) describes a universal pathophysiological phenomenon and mechanism in which macromolecular compounds such as albumin and other polymer-conjugated drugs beyond certain sizes (above 40 kDa) can progressively accumulate in the tumor vascularized area and thus achieve targeting delivery and retention of anticancer compounds into solid tumor tissue. Targeting therapy via the EPR effect in clinical practice is not always successful since the strength of the EPR effect varies depending on the type and location of tumors, status of blood perfusion in tumors, and the physical-chemical properties of macromolecular anticancer agents. This review highlights the significance of the concept and mechanism of the EPR effect and discusses methods for better utilizing the EPR effect in developing smarter macromolecular nanomedicine to achieve a satisfactory outcome in clinical applications.

scholarly journals EPR effect based nanocarriers targeting for treatment of cancer

2017 ◽  
Vol 8 (4) ◽  
Author(s):  
Kavita Rai Gajbhiye ◽  
J M Gajbhiye
Keyword(s):  
Solid Tumors ◽  
Molecular Mechanisms ◽  
Drug Effects ◽  
Vascular Density ◽  
Epr Effect ◽  
Normal Tissues ◽  
Enhanced Permeability And Retention ◽  
Macromolecular Drugs ◽  
Intratumoral Delivery

<p>The enhanced permeability and retention (EPR) effect is a unique phenomenon of solid tumors related to their anatomical and pathophysiological differences from normal tissues. In solid tumors, angiogenesis leads to high vascular density. Large gaps exist between endothelial cells in tumor blood vessels, which lead to selective extravasations and retention of macromolecular drugs. This EPR effect served as a basis for development of macromolecular anticancer therapy. There are various factors, which lead to a significantly increased EPR effect and enhanced antitumor drug effects as well. This review discusses the unique anatomy of tumor vessels, molecular mechanisms of factors related to the EPR effect and the role of the EPR effect in the intratumoral delivery of protein and peptide drugs, macromolecular drugs and drug-loaded long-circulating nanocarriers.</p>

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