The most cited articles published since 2010, extracted from Scopus
Volume 62, Issue 3, March 2010, Pages 284-304
Omid Veiseh | Jonathan W. Gunn | Miqin Zhang
Magnetic nanoparticles (MNPs) represent a class of non-invasive imaging agents that have been developed for magnetic resonance (MR) imaging. These MNPs have traditionally been used for disease imaging via passive targeting, but recent advances have opened the door to cellular-specific targeting, drug delivery, and multi-modal imaging by these nanoparticles. As more elaborate MNPs are envisioned, adherence to proper design criteria (e.g. size, coating, molecular functionalization) becomes even more essential. This review summarizes the design parameters that affect MNP performance in vivo, including the physicochemical properties and nanoparticle surface modifications, such as MNP coating and targeting ligand functionalizations that can enhance MNP management of biological barriers. A careful review of the chemistries used to modify the surfaces of MNPs is also given, with attention paid to optimizing the activity of bound ligands while maintaining favorable physicochemical properties. © 2009 Elsevier B.V. All rights reserved.
Volume 63, Issue 3, March 2011, Pages 136-151
Jun Fang | Hideaki Nakamura | Hiroshi Maeda
The enhanced permeability and retention (EPR) effect is a unique phenomenon of solid tumors related to their anatomical and pathophysiological differences from normal tissues. For example, angiogenesis leads to high vascular density in solid tumors, large gaps exist between endothelial cells in tumor blood vessels, and tumor tissues show selective extravasation and retention of macromolecular drugs. This EPR effect served as a basis for development of macromolecular anticancer therapy. We demonstrated methods to enhance this effect artificially in clinical settings. Of great importance was increasing systolic blood pressure via slow angiotensin II infusion. Another strategy involved utilization of NO-releasing agents such as topical nitroglycerin, which releases nitrite. Nitrite is converted to NO more selectively in the tumor tissues, which leads to a significantly increased EPR effect and enhanced antitumor drug effects as well. This review discusses 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. © 2010 Elsevier B.V.
Volume 62, Issue 1, January 2010, Pages 83-99
Narayan Bhattarai | Jonathan W. Gunn | Miqin Zhang
Hydrogels are high-water content materials prepared from cross-linked polymers that are able to provide sustained, local delivery of a variety of therapeutic agents. Use of the natural polymer, chitosan, as the scaffold material in hydrogels has been highly pursued thanks to the polymer's biocompatibility, low toxicity, and biodegradability. The advanced development of chitosan hydrogels has led to new drug delivery systems that release their payloads under varying environmental stimuli. In addition, thermosensitive hydrogel variants have been developed to form a chitosan hydrogel in situ, precluding the need for surgical implantation. The development of these intelligent drug delivery devices requires a foundation in the chemical and physical characteristics of chitosan-based hydrogels, as well as the therapeutics to be delivered. In this review, we investigate the newest developments in chitosan hydrogel preparation and define the design parameters in the development of physically and chemically cross-linked hydrogels. © 2009 Elsevier B.V. All rights reserved.
Volume 63, Issues 1-2, January 2011, Pages 24-46
Morteza Mahmoudi | Shilpa V. Sant | Ben Wang | Sophie Laurent | Tapas Sen
At present, nanoparticles are used for various biomedical applications where they facilitate laboratory diagnostics and therapeutics. More specifically for drug delivery purposes, the use of nanoparticles is attracting increasing attention due to their unique capabilities and their negligible side effects not only in cancer therapy but also in the treatment of other ailments. Among all types of nanoparticles, biocompatible superparamagnetic iron oxide nanoparticles (SPIONs) with proper surface architecture and conjugated targeting ligands/proteins have attracted a great deal of attention for drug delivery applications. This review covers recent advances in the development of SPIONs together with their possibilities and limitations from fabrication to application in drug delivery. In addition, the state-of-the-art synthetic routes and surface modification of desired SPIONs for drug delivery purposes are described. © 2010 Elsevier B.V.
Volume 63, Issue 3, March 2011, Pages 131-135
Vladimir P. Torchilin
Enhanced permeability and retention (EPR) effect is the physiology-based principal mechanism of tumor accumulation of large molecules and small particles. This specific issue of Advanced Drug Delivery Reviews is summing up multiple data on the EPR effect-based drug design and clinical outcome. In this commentary, 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 EPR effect-mediated accumulation of drug-containing macromolecular systems in tumors. © 2010 Elsevier B.V.
Volume 62, Issue 1, January 2010, Pages 12-27
Shirui Mao | Wei Sun | Thomas H. Kissel
Among non-viral vectors, chitosan and chitosan derivatives have been developed in vitro and in vivo for DNA and siRNA delivery systems because of their cationic charge, biodegradability and biocompatibility, as well as their mucoadhesive and permeability-enhancing properties. However, the transfection efficiency of chitosan is too low for clinical application. Studies indicated that the transfection efficiency depends on a series of chitosan-based formulation parameters, such as the Mw of chitosan, its degree of deacetylation, the charge ratio of chitosan to DNA/siRNA (N/P ratio), the chitosan salt form used, the DNA/siRNA concentration, pH, serum, additives, preparation techniques of chitosan/nucleic acid particles and routes of administration. In this paper, chitosan-based formulations for the delivery of DNA and siRNA were reviewed to facilitate the process of chitosan vector development for clinical application. In addition to formulation optimization, chitosan structure modification or additive incorporation is an effective way to improve the stability of the polyplex in biological fluids, enhance targeted cell delivery and facilitate endo-lysosomal release of the complex. In summary, the transfection efficiency of chitosan-based delivery systems can be adjusted by changing formulation-related parameters. © 2009 Elsevier B.V. All rights reserved.
Volume 62, Issue 1, January 2010, Pages 3-11
Thomas J. Kean | Maya M. Thanou
Chitosan is a natural polysaccharide that has attracted significant scientific interest during the last two decades. It is a potentially biologically compatible material that is chemically versatile (-NH2 groups and various Mw). These two basic properties have been used by drug delivery and tissue engineering scientists to create a plethora of formulations and scaffolds that show promise in healthcare. Despite the high number of published studies, chitosan is not approved by the FDA for any product in drug delivery, and as a consequence very few biotech companies are using this material. This review will aim to provide information on these biological properties that affect chitosan's safe use in drug delivery. The term "Chitosan" represents a large group of structurally different chemical entities that may show different biodistribution, biodegradation and toxicological profiles. Here we aim to review research in this area and critically discuss chitosan's potential to be used as a generally regarded as safe (GRAS) material. © 2009 Elsevier B.V. All rights reserved.
Volume 62, Issue 11, August 2010, Pages 1052-1063
Siti Mohd Janib | Ara S. Moses | John Andrew Mackay
Nanoparticle technologies are significantly impacting the development of both therapeutic and diagnostic agents. At the intersection between treatment and diagnosis, interest has grown in combining both paradigms into clinically effective formulations. This concept, recently coined as theranostics, is highly relevant to agents that target molecular biomarkers of disease and is expected to contribute to personalized medicine. Here we review state-of-the-art nanoparticles from a therapeutic and a diagnostic perspective and discuss challenges in bringing these fields together. Major classes of nanoparticles include, drug conjugates and complexes, dendrimers, vesicles, micelles, core-shell particles, microbubbles, and carbon nanotubes. Most of these formulations have been described as carriers of either drugs or contrast agents. To observe these formulations and their interactions with disease, a variety of contrast agents have been used, including optically active small molecules, metals and metal oxides, ultrasonic contrast agents, and radionuclides. The opportunity to rapidly assess and adjust treatment to the needs of the individual offers potential advantages that will spur the development of theranostic agents. © 2010 Elsevier B.V.
Volume 62, Issue 11, August 2010, Pages 1064-1079
Jin Xie | Seulki Lee | Xiaoyuan Chen
Theranostic nanomedicine is emerging as a promising therapeutic paradigm. It takes advantage of the high capacity of nanoplatforms to ferry cargo and loads onto them both imaging and therapeutic functions. The resulting nanosystems, capable of diagnosis, drug delivery and monitoring of therapeutic response, are expected to play a significant role in the dawning era of personalized medicine, and much research effort has been devoted toward that goal. A convenience in constructing such function-integrated agents is that many nanoplatforms are already, themselves, imaging agents. Their well-developed surface chemistry makes it easy to load them with pharmaceutics and promote them to be theranostic nanosystems. Iron oxide nanoparticles, quantum dots, carbon nanotubes, gold nanoparticles and silica nanoparticles, have been previously well investigated in the imaging setting and are candidate nanoplatforms for building up nanoparticle-based theranostics. In the current article, we will outline the progress along this line, organized by the category of the core materials. We will focus on construction strategies and will discuss the challenges and opportunities associated with this emerging technology. © 2010.
Volume 63, Issue 9, August 2011, Pages 789-808
Challa Satish S R Kumar | Faruq Z. Mohammad
Previous attempts to review the literature on magnetic nanomaterials for hyperthermia-based therapy focused primarily on magnetic fluid hyperthermia (MFH) using mono metallic/metal oxide nanoparticles. The term "hyperthermia" in the literature was also confined only to include use of heat for therapeutic applications. Recently, there have been a number of publications demonstrating magnetic nanoparticle-based hyperthermia to generate local heat resulting in the release of drugs either bound to the magnetic nanoparticle or encapsulated within polymeric matrices. In this review article, we present a case for broadening the meaning of the term "hyperthermia" by including thermotherapy as well as magnetically modulated controlled drug delivery. We provide a classification for controlled drug delivery using hyperthermia: Hyperthermia-based controlled drug delivery through bond breaking (DBB) and hyperthermia-based controlled drug delivery through enhanced permeability (DEP). The review also covers, for the first time, core-shell type magnetic nanomaterials, especially nanoshells prepared using layer-by-layer self-assembly, for the application of hyperthermia-based therapy and controlled drug delivery. The highlight of the review article is to portray potential opportunities for the combination of hyperthermia-based therapy and controlled drug release paradigms -towards successful application in personalized medicine. © 2011 Elsevier B.V.
Volume 62, Issue 1, January 2010, Pages 28-41
Jaehyung Park | Gurusamy Saravanakumar | Kwangmeyung Kim | Ickchan Kwon
Chitosan has prompted the continuous impetus for the development of safe and effective drug delivery systems because of its unique physicochemical and biological characteristics. The primary hydroxyl and amine groups located on the backbone of chitosan allow for chemical modification to control its physical properties. When the hydrophobic moiety is conjugated to a chitosan molecule, the resulting amphiphile may form self-assembled nanoparticles that can encapsulate a quantity of drugs and deliver them to a specific site of action. Chemical attachment of the drug to the chitosan throughout the functional linker may produce useful prodrugs, exhibiting the appropriate biological activity at the target site. Mucoadhesive and absorption enhancement properties of chitosan increase the in vivo residence time of the dosage form in the gastrointestinal tract and improve the bioavailability of various drugs. The main objective of this review is to provide an insight into various target-specific carriers, based on chitosan and its derivatives, towards low molecular weight drug delivery. The first part of the review is concerned with the organ-specific delivery of low molecular drugs using chitosan and its derivatives. The subsequent section considers the recent developments of drug delivery carriers for cancer therapy with special focus on various targeting strategies. © 2009 Elsevier B.V. All rights reserved.
Volume 65, Issue 1, January 2013, Pages 36-48
Theresa M. Allen | Pieter R. R. Cullis
The first closed bilayer phospholipid systems, called liposomes, were described in 1965 and soon were proposed as drug delivery systems. The pioneering work of countless liposome researchers over almost 5 decades led to the development of important technical advances such as remote drug loading, extrusion for homogeneous size, long-circulating (PEGylated) liposomes, triggered release liposomes, liposomes containing nucleic acid polymers, ligand-targeted liposomes and liposomes containing combinations of drugs. These advances have led to numerous clinical trials in such diverse areas as the delivery of anti-cancer, anti-fungal and antibiotic drugs, the delivery of gene medicines, and the delivery of anesthetics and anti-inflammatory drugs. A number of liposomes (lipidic nanoparticles) are on the market, and many more are in the pipeline. Lipidic nanoparticles are the first nanomedicine delivery system to make the transition from concept to clinical application, and they are now an established technology platform with considerable clinical acceptance. We can look forward to many more clinical products in the future. © 2012 Elsevier B.V.
Volume 64, Issue 9, June 2012, Pages 866-884
Emanuel Fleige | Mohiuddin Abdul Quadir | Rainer Haag
The use of polymeric nanocarriers to transport active compounds like small-molecular drugs, peptides, or genes found an increased attention throughout the different fields of natural sciences. Not only that these nanocarriers enhance the properties of already existing drugs in terms of solubility, bioavailability, and prolonged circulation times, furthermore they can be tailor-made in such a manner that they selectively release their cargo at the desired site of action. For the triggered release, these so-called smart drug delivery systems are designed to react on certain stimuli like pH, temperature, redox potential, enzymes, light, and ultrasound. Some of these stimuli are naturally occurring in vivo, for example the difference in pH in different cellular compartments while others are caused by the disease, which is to be treated, like differences in pH and temperature in some tumor tissues. Other external applied stimuli, like light and ultrasound, allow the temporal and spatial control of the release, since they are not triggered by any biological event. This review gives a brief overview about some types of stimuli-responsive nanocarriers with the main focus on organic polymer-based systems. Furthermore, the different stimuli and the design of corresponding responsive nanocarriers will be discussed with the help of selected examples from the literature. © 2012 Elsevier B.V.
Volume 62, Issue 1, January 2010, Pages 59-82
Maryam Amidi | Enrico Mastrobattista | Wim I M Jiskoot | Wim E. Hennink
Therapeutic peptides/proteins and protein-based antigens are chemically and structurally labile compounds, which are almost exclusively administered by parenteral injections. Recently, non-invasive mucosal routes have attracted interest for administration of these biotherapeutics. Chitosan-based delivery systems enhance the absorption and/or cellular uptake of peptides/proteins across mucosal sites and have immunoadjuvant properties. Chitosan is a mucoadhesive polysaccharide capable of opening the tight junctions between epithelial cells and it has functional groups for chemical modifications, which has resulted in a large variety of chitosan derivatives with tunable properties for the aimed applications. This review provides an overview of chitosan-based polymers for preparation of both therapeutic peptides/protein and antigen formulations. The physicochemical properties of these carrier systems as well as their applications in protein and antigen delivery through parenteral and mucosal (particularly nasal and pulmonary) administrations are summarized and discussed. © 2009 Elsevier B.V. All rights reserved.
Volume 62, Issue 3, March 2010, Pages 362-374
Bengt Fadeel | Alfonso E. García-Bennett
The development of nanoparticles for biomedical applications including medical imaging and drug delivery is currently undergoing a dramatic expansion. However, as the range of nanoparticle types and applications increases, it is also clear that the potential toxicities of these novel materials and the properties driving such toxic responses must also be understood. Indeed, a detailed assessment of the factors that influence the biocompatibility and/or toxicity of nanoparticles is crucial for the safe and sustainable development of the emerging nanotechnologies. This review summarizes some of the recent developments in the field of nanomedicine with particular emphasis on inorganic nanoparticles for drug delivery. The synthesis routes, physico-chemical characteristics, and cytotoxic properties of inorganic nanoparticles are thus explored and lessons learned from the toxicological investigation of three common types of engineered nanomaterials of titania, gold, and mesoporous silica are discussed. Emphasis is placed on the recognition versus non-recognition of engineered nanomaterials by the immune system, the primary surveillance system against microorganisms and particles, which, in turn, is intimately linked to the issue of targeted drug delivery using such nanomaterials as carrier systems. © 2009 Elsevier B.V. All rights reserved.
Volume 63, Issue 3, March 2011, Pages 170-183
Sarbari Acharya | Sanjeeb Kumar Sahoo
As mortality due to cancer continues to rise, advances in nanotechnology have significantly become an effective approach for achieving efficient drug targeting to tumour tissues by circumventing all the shortcomings of conventional chemotherapy. During the past decade, the importance of polymeric drug-delivery systems in oncology has grown exponentially. In this context, poly(lactic- co-glycolic acid) (PLGA) is a widely used polymer for fabricating 'nanoparticles' because of biocompatibility, long-standing track record in biomedical applications and well-documented utility for sustained drug release, and hence has been the centre of focus for developing drug-loaded nanoparticles for cancer therapy. Such PLGA nanoparticles have also been used to develop proteins and peptides for nanomedicine, and nanovaccines, as well as a nanoparticle-based drug- and gene-delivery system for cancer therapy, and nanoantigens and growth factors. These drug-loaded nanoparticles extravasate through the tumour vasculature, delivering their payload into the cells by the enhanced permeability and retention (EPR) effect, thereby increasing their therapeutic effect. Ongoing research about drug-loaded nanoparticles and their delivery by the EPR effect to the tumour tissues has been elucidated in this review with clarity. © 2010 Elsevier B.V.
Volume 63, Issue 9, August 2011, Pages 730-747
Mihaela Delcea | Helmuth M. Möhwald | André G. Skirtach
Review of basic principles and recent developments in the area of stimuli responsive polymeric capsules and nanoshells formed via layer-by-layer (LbL) is presented. The most essential attributes of the LbL approach are multifunctionality and responsiveness to a multitude of stimuli. The stimuli can be logically divided into three categories: physical (light, electric, magnetic, ultrasound, mechanical, and temperature), chemical (pH, ionic strength, solvent, and electrochemical) and biological (enzymes and receptors). Using these stimuli, numerous functionalities of nanoshells have been demonstrated: encapsulation, release including that inside living cells or in tissue, sensors, enzymatic reactions, enhancement of mechanical properties, and fusion. This review describes mechanisms and basic principles of stimuli effects, describes progress in the area, and gives an outlook on emerging trends such as theranostics and nanomedicine. © 2011 Elsevier B.V.
Volume 62, Issue 2, February 2010, Pages 122-149
Jindřich I. Kopeček | Pavla Kopečková
The overview covers the discovery of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers, initial studies on their synthesis, evaluation of biological properties, and explorations of their potential as carriers of biologically active compounds in general and anticancer drugs in particular. The focus is on the research in the authors' laboratory - the development of macromolecular therapeutics for the treatment of cancer and musculoskeletal diseases. In addition, the evaluation of HPMA (co)polymers as building blocks of modified and new biomaterials is presented: the utilization of semitelechelic poly(HPMA) and HPMA copolymers for the modification of biomaterial and protein surfaces and the design of hybrid block and graft HPMA copolymers that self-assemble into smart hydrogels. Finally, suggestions for the design of second-generation macromolecular therapeutics are portrayed. © 2009 Elsevier B.V. All rights reserved.
Volume 63, Issue 3, March 2011, Pages 152-160
Hiroto Hatakeyama | Hidetaka Akita | Hideyoshi Harashima
Gene and nucleic acid therapy are expected to play a major role in the next generation of medicine. We recently developed a multifunctional envelope-type nano device (MEND) for use as a novel non-viral gene delivery system. Poly(ethylene glycol) (PEG)ylation is a useful method for achieving a longer circulation time for delivery of the MEND to a tumour via the enhanced permeability and retention (EPR) effect. However, PEGylation strongly inhibits cellular uptake and endosomal escape, which results in significant loss of activity for the delivery system. For successful gene delivery for cancer treatment, the crucial issue associated with the use of PEG, the 'PEG dilemma' must be addressed. In this review, we describe the development and applications of MEND, and discuss strategies for overcoming the PEG dilemma, based on the manipulation of intracellular trafficking of cellular uptake and endosomal release using functional devices such as specific ligands, cleavable PEG systems and endosomal fusogenic/disruptic peptides. © 2010 Elsevier B.V.
Volume 63, Issue 4, April 2011, Pages 300-311
Esther C. Novosel | Claudia Kleinhans | Petra J. Kluger
The main limitation in engineering in vitro tissues is the lack of a sufficient blood vessel system - the vascularization. In vivo almost all tissues are supplied by these endothelial cell coated tubular networks. Current strategies to create vascularized tissues are discussed in this review. The first strategy is based on the endothelial cells and their ability to form new vessels known as neoangiogenesis. Herein prevascularization techniques are compared to approaches in which biomolecules, such as growth factors, cytokines, peptides and proteins as well as cells are applied to generate new vessels. The second strategy is focused on scaffold-based techniques. Naturally-derived scaffolds, which contain vessels, are distinguished from synthetically manufactured matrices. Advantages and pitfalls of the approaches to create vascularized tissues in vitro are outlined and feasible future strategies are discussed. © 2010 Elsevier B.V.
Volume 62, Issue 3, March 2010, Pages 339-345
Paul Cherukuri | Evan S. Glazer | Steven Curley
Despite the use of hyperthermia to treat cancer for thousands of years, the challenge of only heating malignant cells remains daunting. In pre-clinical and early clinical trials, metal nanoparticles induce hyperthermic cytotoxicity when exposed to near-infrared radiation or radiofrequency fields. We discuss the emerging roles of nanoparticles, especially gold, in the hyperthermic treatment of cancer. In addition, we discuss the similarities of radiofrequency ablation and nanoparticle mediated cytotoxicity. © 2009 Elsevier B.V. All rights reserved.
Volume 63, Issue 6, May 2011, Pages 427-440
Elaine M. Merisko-Liversidge | Gary G. Liversidge
A significant percentage of active pharmaceutical ingredients identified through discovery screening programs is poorly soluble in water. These molecules are often difficult to formulate using conventional approaches and are associated with innumerable formulation-related performance issues, e.g. poor bioavailability, lack of dose proportionality, slow onset of action and other attributes leading to poor patient compliance. In addition, for parenteral products, these molecules are generally administered with co-solvents and thus have many undesirable side effects. Wet media milling is one of the leading particle size reduction approaches that have been successfully used to formulate these problematic compounds. The approach is a water-based media milling process where micron-sized drug particles are shear-fractured into nanometer-sized particles. Nanoparticle dispersions are stable and typically have a mean diameter of less than 200. nm with 90% of the particles being less than 400. nm. The formulation consists only of water, drug and one or more GRAS excipients. Drug concentrations approaching 300-400. mg/g can be targeted with the use of minimal amounts stabilizer. Typically, on average, the drug to stabilizer ratio on a weight basis ranges from 2:1 to 20:1. These liquid nanodispersions exhibit acceptable shelf-life and can be post-processed into various types of solid dosage forms. Nanoparticulate-based drug products have been shown to improve bioavailability and enhance drug exposure for oral and parenteral dosage forms. Suitable formulations for the most commonly used routes of administration can be identified with milligram quantities of drug substance providing the discovery scientist an alternate avenue for screening and identifying superior leads. In the last few years, formulating poorly water soluble compounds as nanosuspensions has evolved from a conception to a realization. The versatility and applicability of this drug delivery platform are just beginning to be realized. © 2011 Elsevier B.V.
Volume 63, Issue 6, May 2011, Pages 470-491
Tarl W. Prow | Jeffrey Ernest Grice | Lynlee L. Lin | Rokhaya Faye | Margaret K. Butler | Wolfgang S. Becker | Elisabeth Mt T Wurm | Corinne Yoong | Thomas A. Robertson | H. Peter Soyer | Michael S. Roberts
Skin is a widely used route of delivery for local and systemic drugs and is potentially a route for their delivery as nanoparticles. The skin provides a natural physical barrier against particle penetration, but there are opportunities to deliver therapeutic nanoparticles, especially in diseased skin and to the openings of hair follicles. Whilst nanoparticle drug delivery has been touted as an enabling technology, its potential in treating local skin and systemic diseases has yet to be realised. Most drug delivery particle technologies are based on lipid carriers, i.e. solid lipid nanoparticles and nanoemulsions of around 300. nm in diameter, which are now considered microparticles. Metal nanoparticles are now recognized for seemingly small drug-like characteristics, i.e. antimicrobial activity and skin cancer prevention. We present our unpublished clinical data on nanoparticle penetration and previously published reports that support the hypothesis that nanoparticles > 10. nm in diameter are unlikely to penetrate through the stratum corneum into viable human skin but will accumulate in the hair follicle openings, especially after massage. However, significant uptake does occur after damage and in certain diseased skin. Current chemistry limits both atom by atom construction of complex particulates and delineating their molecular interactions within biological systems. In this review we discuss the skin as a nanoparticle barrier, recent work in the field of nanoparticle drug delivery to the skin, and future directions currently being explored. © 2011 Elsevier B.V.
Volume 64, Issue 2, February 2012, Pages 190-199
Alaaldin M. Alkilany | Lucas B. Thompson | Stefano P. Boulos | Patrick N. Sisco | Catherine Jones Murphy
Gold nanorods have promising applications in the fields of drug delivery and photothermal therapy. These promises arise from the nanorods' unique optical and photothermal properties, the availability of synthetic protocols that can tune the size and shape of the particles, the ability to modify the surface and conjugate drugs/molecules to the nanorods, and the relative biocompatibility of gold nanorods. In this review, current progress in using gold nanorods as phototherapeutic agents and as drug delivery vehicles is summarized. Issues of dosage, toxicity and biological interactions at three levels (biological media alone; cells; whole organisms) are discussed, concluding with recommendations for future work in this area. © 2011 Elsevier B.V.
Volume 65, Issue 1, January 2013, Pages 71-79
Hiroshi Maeda | Hideaki Nakamura | Jun Fang
The EPR effect results from the extravasation of macromolecules or nanoparticles through tumor blood vessels. We here provide a historical review of the EPR effect, including its features, vascular mediators found in both cancer and inflamed tissue. In addition, architectural and physiological differences of tumor blood vessels vs that of normal tissue are commented. Furthermore, methods of augmentation of the EPR effect are described, that result in better tumor delivery and improved therapeutic effect, where nitroglycerin, angiotensin I-converting enzyme (ACE) inhibitor, or angiotensin II-induced hypertension are employed. Consequently, better therapeutic effect and reduced systemic toxicity are generally observed. Obviously, the EPR effect based delivery of nanoprobes are also useful for tumor-selective imaging agents with using fluorescent or radio nuclei in nanoprobes. We also commented a key difference between passive tumor targeting and the EPR effect in tumors, particularly as related to drug retention in tumors: passive targeting of low-molecular-weight X-ray contrast agents involves a retention period of less than a few minutes, whereas the EPR effect of nanoparticles involves a prolonged retention time-days to weeks. © 2012 Elsevier B.V.