Exploiting the enhanced permeability and retention effect for tumor targeting.
TL;DR: Various endogenous factors that can positively impact the EPR effect in tumor tissues are discussed, as well as practical methods available in the clinical setting for augmenting the effect by use of exogenous agents.
About: This article is published in Drug Discovery Today.The article was published on 2006-09-01. It has received 1701 citations till now. The article focuses on the topics: Enhanced permeability and retention effect.
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TL;DR: Molecular mechanisms of factors related to the EPR effect, the unique anatomy of tumor vessels, limitations and techniques to avoid such limitations, augmenting tumor drug delivery, and experimental and clinical findings are discussed.
3,034 citations
TL;DR: It is argued that gold nanotechnology-enabled biomedicine is not simply an act of 'gilding the (nanomedicinal) lily', but that a new 'Golden Age' of biomedical nanotechnology is truly upon us.
Abstract: Gold nanoparticles have been used in biomedical applications since their first colloidal syntheses more than three centuries ago. However, over the past two decades, their beautiful colors and unique electronic properties have also attracted tremendous attention due to their historical applications in art and ancient medicine and current applications in enhanced optoelectronics and photovoltaics. In spite of their modest alchemical beginnings, gold nanoparticles exhibit physical properties that are truly different from both small molecules and bulk materials, as well as from other nanoscale particles. Their unique combination of properties is just beginning to be fully realized in range of medical diagnostic and therapeutic applications. This critical review will provide insights into the design, synthesis, functionalization, and applications of these artificial molecules in biomedicine and discuss their tailored interactions with biological systems to achieve improved patient health. Further, we provide a survey of the rapidly expanding body of literature on this topic and argue that gold nanotechnology-enabled biomedicine is not simply an act of ‘gilding the (nanomedicinal) lily’, but that a new ‘Golden Age’ of biomedical nanotechnology is truly upon us. Moving forward, the most challenging nanoscience ahead of us will be to find new chemical and physical methods of functionalizing gold nanoparticles with compounds that can promote efficient binding, clearance, and biocompatibility and to assess their safety to other biological systems and their long-term term effects on human health and reproduction (472 references).
2,712 citations
TL;DR: Delivery of conventional chemotherapeutic anti-cancer drugs is mainly discussed and exploitation and the understanding of these characteristics to design new drug delivery systems targeting the tumor are focused on.
2,272 citations
Cites background from "Exploiting the enhanced permeabilit..."
...Very high local concentrations of drug-loaded nanocarriers can be achieved at the tumor site, for instance 10–50-fold higher than in normal tissue within 1–2 days [34]....
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TL;DR: The role of the EPR effect in the intratumoral delivery of protein and peptide drugs, macromolecular drugs and drug-loaded long-circulating pharmaceutical nanocarriers is briefly discussed together with some additional opportunities for drug delivery arising from the initial EPReffect-mediated accumulation of drug-containing macromolescular systems in tumors.
1,746 citations
TL;DR: The current status of the use of nanoparticles for photothermal treatments is reviewed in detail, paying special attention to the physical mechanisms at the root of the light-to-heat conversion processes.
Abstract: The current status of the use of nanoparticles for photothermal treatments is reviewed in detail. The different families of heating nanoparticles are described paying special attention to the physical mechanisms at the root of the light-to-heat conversion processes. The heating efficiencies and spectral working ranges are listed and compared. The most important results obtained in both in vivo and in vitro nanoparticle assisted photothermal treatments are summarized. The advantages and disadvantages of the different heating nanoparticles are discussed.
1,441 citations
References
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Book•
01 Jan 1966
TL;DR: Textbook of medical physiology , Textbook ofmedical physiology , کتابخانه دیجیتال جندی شاپور اهواز
Abstract: Textbook of medical physiology , Textbook of medical physiology , کتابخانه دیجیتال جندی شاپور اهواز
10,145 citations
TL;DR: Textbook of medical physiology, Textbook of Medical Physiology, this paper, textbook of medicine, textbooks of medical science, text book of medical literature, textbook medical physiology.
9,914 citations
TL;DR: Think of the switch to the angiogenic phenotype as a net balance of positive and negative regulators of blood vessel growth, which may dictate whether a primary tumour grows rapidly or slowly and whether metastases grow at all.
Abstract: Recent discoveries of endogenous negative regulators of angiogenesis, thrombospondin, angiostatin and glioma-derived angiogenesis inhibitory factor, all associated with neovascularized tumours, suggest a new paradigm of tumorigenesis. It is now helpful to think of the switch to the angiogenic phenotype as a net balance of positive and negative regulators of blood vessel growth. The extent to which the negative regulators are decreased during this switch may dictate whether a primary tumour grows rapidly or slowly and whether metastases grow at all.
7,916 citations
Journal Article•
TL;DR: It is speculated that the tumoritropic accumulation of smancs and other proteins resulted because of the hypervasculature, an enhanced permeability to even macromolecules, and little recovery through either blood vessels or lymphatic vessels in tumors of tumor-bearing mice.
Abstract: We previously found that a polymer conjugated to the anticancer protein neocarzinostatin, named smancs, accumulated more in tumor tissues than did neocarzinostatin. To determine the general mechanism of this tumoritropic accumulation of smancs and other proteins, we used radioactive (51Cr-labeled) proteins of various molecular sizes (Mr 12,000 to 160,000) and other properties. In addition, we used dye-complexed serum albumin to visualize the accumulation in tumors of tumor-bearing mice. Many proteins progressively accumulated in the tumor tissues of these mice, and a ratio of the protein concentration in the tumor to that in the blood of 5 was obtained within 19 to 72 h. A large protein like immunoglobulin G required a longer time to reach this value of 5. The protein concentration ratio in the tumor to that in the blood of neither 1 nor 5 was achieved with neocarzinostatin, a representative of a small protein (Mr 12,000) in all time. We speculate that the tumoritropic accumulation of these proteins resulted because of the hypervasculature, an enhanced permeability to even macromolecules, and little recovery through either blood vessels or lymphatic vessels. This accumulation of macromolecules in the tumor was also found after i.v. injection of an albumin-dye complex (Mr 69,000), as well as after injection into normal and tumor tissues. The complex was retained only by tumor tissue for prolonged periods. There was little lymphatic recovery of macromolecules from tumor tissue. The present finding is of potential value in macromolecular tumor therapeutics and diagnosis.
6,483 citations
TL;DR: DNA sequencing suggests the existence of several molecular species of VEGF, a heparin-binding growth factor specific for vascular endothelial cells that is able to induce angiogenesis in vivo.
Abstract: Vascular endothelial growth factor (VEGF) was purified from media conditioned by bovine pituitary folliculostellate cells (FC). VEGF is a heparin-binding growth factor specific for vascular endothelial cells that is able to induce angiogenesis in vivo. Complementary DNA clones for bovine and human VEGF were isolated from cDNA libraries prepared from FC and HL60 leukemia cells, respectively. These cDNAs encode hydrophilic proteins with sequences related to those of the A and B chains of platelet-derived growth factor. DNA sequencing suggests the existence of several molecular species of VEGF. VEGFs are secreted proteins, in contrast to other endothelial cell mitogens such as acidic or basic fibroblast growth factors and platelet-derived endothelial cell growth factor. Human 293 cells transfected with an expression vector containing a bovine or human VEGF cDNA insert secrete an endothelial cell mitogen that behaves like native VEGF.
5,092 citations
"Exploiting the enhanced permeabilit..." refers background in this paper
...26 Matsumura, Y. et al. (1991) Kinin-generating cascade in advanced cancer patients and in vitro study....
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...82, 732–741 27 Wu, J. et al. (2002) Identification of bradykinin receptors in clinical cancer specimens and murine tumor tissues....
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