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Advanced Drug Delivery Reviews (v.58, #14)
Nanomedicine: Developing smarter therapeutic and diagnostic modalities by Omid C. Farokhzad; Robert Langer (pp. 1456-1459).
The early impact of nanotechnology on medicine is beginning to get realized, with novel nanoscale therapeutic and diagnostic modalities under development or in clinical practice today. In this commentary the field of “nanomedicine� is briefly reviewed form the perspective of where we were; where we are today; and where we are likely to go tomorrow.
Keywords: Nanomedicine; Nanoparticle; Targeted; Diagnostic; Therapeutic
Carbon nanotubes as nanomedicines: From toxicology to pharmacology by Lara Lacerda; Alberto Bianco; Maurizio Prato; Kostas Kostarelos (pp. 1460-1470).
Various biomedical applications of carbon nanotubes have been proposed in the last few years leading to the emergence of a new field in diagnostics and therapeutics. Most of these applications will involve the administration or implantation of carbon nanotubes and their matrices into patients. The toxicological and pharmacological profile of such carbon nanotube systems developed as nanomedicines will have to be determined prior to any clinical studies undertaken. This review brings together all the toxicological and pharmacological in vivo studies that have been carried out using carbon nanotubes, to offer the first summary of the state-of-the-art in the pharmaceutical development of carbon nanotubes on the road to becoming viable and effective nanomedicines.
Keywords: Toxicology; Biodistribution; Pharmacokinetics; Cancer nanotechnology
Recent advances in iron oxide nanocrystal technology for medical imaging by Claire Corot; Philippe Robert; Jean-Marc Idée; Marc Port (pp. 1471-1504).
Superparamagnetic iron oxide particles (SPIO and USPIO) have a variety of applications in molecular and cellular imaging. Most of the recent research has concerned cellular imaging with imaging of in vivo macrophage activity. According to the iron oxide nanoparticle composition and size which influence their biodistribution, several clinical applications are possible: detection liver metastases, metastatic lymph nodes, inflammatory and/or degenerative diseases. USPIO are investigated as blood pool agents with T1 weighted sequence for angiography, tumour permeability and tumour blood volume or steady-state cerebral blood volume and vessel size index measurements using T2â?Ž weighted sequences. Stem cell migration and immune cell trafficking, as well as targeted iron oxide nanoparticles for molecular imaging studies, are at the stage of proof of concept, mainly in animal models.
Keywords: USPIO; Iron oxide nanoparticles; MRI macrophage imaging; MR-cell tracking; MR-molecular imaging
Virus-based nanoparticles (VNPs): Platform technologies for diagnostic imaging by Marianne Manchester; Pratik Singh (pp. 1505-1522).
Non-invasive imaging holds great promise for the early detection and treatment of human disease. The ability to both detect and follow disease processes or anatomical defects without biopsy, surgery, or other invasive techniques should lead to lower costs and higher quality of life. The use of “smart� nanoparticles, that combine multiple functions of targeting, imaging, and drug delivery, have tremendous potential to increase the sensitivity and specificity of therapies. These will facilitate early detection and reduce adverse side effects of treatment. There are many different classes of nanoparticles in development including dendrimers, liposomes, paramagnetic nanoparticles, and quantum dots, to name just a few. Here we focus on virus-based nanoparticles (VNPs) as platforms for the development of tissue-specific targeting and imaging agents in vivo.
Keywords: Virus; Nanoparticle; VNP; Imaging; Tumor; Vascular; Nanotechnology; CPMV
Molecular hurdles in polyfectin design and mechanistic background to polycation induced cytotoxicity by A. Christy Hunter (pp. 1523-1531).
Synthetic polymer based Polyfectins (cationic polymer-DNA complex) have received intensive scientific research as they can potentially circumvent problems associated with viral vectors for gene therapy. These cationic macromolecules can readily condense DNA or RNA into stable nanostructures for use in gene delivery. Recently two commonly used polycations, poly(ethylenimine) (PEI) and poly(l-lysine) have demonstrated their ability to induce apoptosis in a range of human cell lines. This may be the explanation for short-term gene transfection observed with polyfectins. It is the aim of this review to discuss these and other factors behind observed toxicities including the inherent polydisperse nature of polymeric macromolecules and their behaviour in vivo. Strategies for reduction of toxicity are included such as new polymeric synthetic technologies and vector pegylation. There is a clear and immediate need for understanding of the mechanisms which cause polyfectin toxicity which will ultimately facilitate improved vector design and safer gene delivery.
Keywords: Polyfectin; Polymer toxicity; Gene therapy; Apoptosis; MTT assay; Poly(ethylenimine); Poly(; l; -lysine); Biodegradable polymer; Gene transfection
Multifunctional nanocarriers by Vladimir P. Torchilin (pp. 1532-1555).
Currently used pharmaceutical nanocarriers, such as liposomes, micelles, nanoemulsions, polymeric nanoparticles and many others demonstrate a broad variety of useful properties, such as longevity in the blood allowing for their accumulation in pathological areas with compromised vasculature; specific targeting to certain disease sites due to various targeting ligands attached to the surface of the nanocarriers; enhanced intracellular penetration with the help of surface-attahced cell-penetrating molecules; contrast properties due to the carrier loading with various contrast materials allowing for direct carrier visualization in vivo; stimuli-sensitivity allowing for drug release from the carriers under certain physiological conditions, and others. Some of those pharmaceutical carriers have already made their way into clinic, while others are still under preclinical development. What could be seen much more rare, however, are the pharmaceutical nanocarriers combining several from the listed abilities. Long-circulating immunoliposomes capable of prolonged residence in the blood and specific target recognition represent one of few examples of this kind. At the same time, the enginnering of multifunctional pharmaceutical nanocarriers combinig several useful preoperties in one particle can significantly enhance the efficacy of many therapeutic and diagnostic protocols. This paper considers current status and possible future directions in the emerging area of multifunctional nanocarriers with primary attention on the combination of such properties as longevity, targetability, intracellular penetration and contrast loading.
Keywords: Nanomedicine; Pharmaceutical carriers; Drug delivery; Drug targeting; Long-circulating drug carriers; Imaging; Intracellular drug delivery; Liposomes; Micelles; Polymeric nanoparticles
Brain cancer diagnosis and therapy with nanoplatforms by Yong-Eun Lee Koo; G. Ramachandra Reddy; Mahaveer Bhojani; Randy Schneider; Martin A. Philbert; Alnawaz Rehemtulla; Brian D. Ross; Raoul Kopelman (pp. 1556-1577).
Treatment of brain cancer remains a challenge despite recent improvements in surgery and multimodal adjuvant therapy. Drug therapies of brain cancer have been particularly inefficient, due to the blood–brain barrier and the non-specificity of the potentially toxic drugs. The nanoparticle has emerged as a potential vector for brain delivery, able to overcome the problems of current strategies. Moreover, multi-functionality can be engineered into a single nanoplatform so that it can provide tumor-specific detection, treatment, and follow-up monitoring. Such multitasking is not possible with conventional technologies. This review describes recent advances in nanoparticle-based detection and therapy of brain cancer. The advantages of nanoparticle-based delivery and the types of nanoparticle systems under investigation are described, as well as their applications.
Keywords: Nanoparticles; Blood–brain barrier; Drug delivery; MRI; Chemotherapy; Photodynamic therapy; Targeting