Dual Purpose Nanoparticles Act as Delivery and Imaging Agents for Cancer Tissue
Researchers have developed a novel cancer-targeting nanoparticle that can potentially act as a drug-delivery agent and a dual imaging agent at the same time. The team, from the University of Central Florida, FL, USA, developed a functionalized iron-oxide nanoparticle capable of encapsulating both an anticancer drug and near-infrared dyes, allowing for the targeted delivery of the drug as well as dual imaging of the cancer cells through optical imaging and MRI.
Successful development of targeted cancer therapeutics is vital, as many current chemotherapy regimens lead to severe systemic toxicity due to the fact that the toxic drugs will kill healthy tissue whilst in circulation, leading to serious adverse side effects including nausea, exhaustion and immunosuppression. Targeted drugs will hopefully reduce adverse reactions by limiting their action to cancer tissue only. Nanoparticles can be easily functionalized to target specific cells types and may be promising delivery and imaging agents in the treatment of cancer.
The team has developed a dual purpose iron-oxide nanoparticle that successfully delivered Taxol® to cells in culture by functionalizing the nanoparticles with a folic acid derivative that allows the nanoparticles to be taken up by cells expressing the appropriate cell receptors, which are overexpressed on many cancer cells. The nanoparticles were also designed as dual imaging agents, allowing for imaging by MRI (due to their iron-oxide core) and by optical imaging, as they can coencapsulate near-infrared dye particles due to a novel fabrication method designed by the team. Importantly, the particles are both biocompatible and biodegradable.
Dr Perez, Assistant Professor at the University of Central Florida and one of the principal investigators of the study commented on the results: “What‘s unique about our work is that the nanoparticle has a dual role, as a diagnostic and therapeutic agent in a biodegradable and biocompatible vehicle.” He stressed that the results from the cell cultures are preliminary but “are very encouraging … Our work is an important beginning, because it demonstrates an avenue for using nanotechnology not only to diagnose but also to treat cancer, potentially at an early stage.”
Source: Santra S, Kaittanis C, Grimm J, Perez JM: Drug/dye-loaded, multifunctional iron oxide nanoparticles for combined targeted cancer therapy and dual optical/magnetic resonance imaging. Small (2009) (Epub ahead of print).
Nanomedicine Market Will Be Worth Us$160 Billion by 2015
Another class of nanoparticles has been shown to cause acute lung injury, adding to the serious concerns about the safety of nanomaterials
A Global Industry Analysts, Inc. report published this month predicted that the nanomedicine industry will rise to over US$160 billion by 2015, fuelled by the unique approaches to medicine offered by nanotechnology.
The nanomedicine industry was split into five key areas in the report: drug delivery, in vitro diagnostics, in vivo imaging, biomaterials and other applications. Drug delivery was the largest of these sectors, although the biomaterials sector is the fastest growing, a trend that the report predicted will continue until the year 2015.
The report, which is around 700 pages long, also contains profiles of 263 nanomedicine companies, including major players from the pharmaceutical industry, such as Amgen, Inc., Johnson & Johnson, Merck & Co., Inc. and Wyeth Pharmaceuticals, Inc., and also some whose scope is narrower or more ‘niche,’ for example Nanobiotix and Nanospectra Biosciences, Inc. It justifies this wide scope by noting that nanomedicine is a ‘fragmented’ industry, characterized by a number of different types of company. With regards to region, the report found that more European nanomedicine companies were based in Germany than in European countries, such as the UK, Switzerland and France, and that China had the most nanomedicine companies in the Asia–Pacific region.
The ‘Trends and Issues’ section of the study highlighted some key challenges for the industry, including the possibilities for nanomedicine strategies in drug discovery, as well as the use of in silico computational modeling methods to develop more efficient nanoparticles.
Source: Nanomedicine: A Global Strategic Business Report, Global Industry Analysts. www.strategyr.com/Nanomedicine_Market_Report.asp
Nanodiamond Strategy Could Help Solve Problem of Water-Insoluble Therapeutics
Many promising therapeutics have been halted in the animal model phase of development as their compounds are water insoluble and thus unable to be safely delivered to patients. However, an innovative nanoparticle strategy using nanodiamonds as a drug-delivery platform has the potential to transport these formerly unsafe therapies to cells.
The team, a collaboration of scientists from Northwestern University, IL, USA, and Shinshu University, Japan, has shown that their synthesized nanodiamonds are able to provide a water-soluble platform for purvalanol A, a liver cancer treatment, 4-hydroxytamoxifen, which has been shown to be effective against breast cancer, and dexamethasone, an anti-inflammatory that can be used to treat blood and brain cancers as well as rheumatic and renal disorders. The drug compounds are able to bind to carboxyl groups, present on the surface of the nanodiamonds after a purification process after their synthesis.
The technique combines the useful properties of nanocarbon (e.g., biocompatibility, dispersibility in water and the ability to be scaled) to solve some of the problems surrounding the water-insoluble therapeutics. Previously the group reported on the use of nanodiamonds to deliver chemotherapy drugs to specific sites where tumors have recently been surgically removed.
“We have shown through multiple modes of characterization, including UV-visible spectrophotometry, TEM imagery and z-potential measurement/dynamic light scattering analysis that the water-insoluble therapeutics physically interact with the nanodiamonds, forming complexes that are capable of dispersing these drugs in water for sustained periods of time while also maintaining their functionality, whereas without the nanodiamonds, the drugs immediately precipitated and were rendered nonfunctional,” explained Assistant Professor Dean Ho, from Northwestern University.
The team‘s experimental efforts are now being supplemented with in silico models to shed more light on the surface properties of nanodiamonds. They are hopeful that the technology will rapidly progress towards clinical efficiency. “This integrative effort generates cross-disciplinary challenges, but also represents a major opportunity to impact the drug delivery and nanomedicine domains, among others,” enthused Professor Ho.
Source: Chen M, Pierstorff ED, Lam R et al.: Nanodiamond-mediated delivery of water-insoluble therapeutics. ACS Nano (2009) (Epub ahead of print).
Polyamidoamine Dendrimers Can Cause Acute Lung Injury In Vivo
Scientists have shown that a common class of dendrimers may cause severe acute lung injury and, importantly, have managed to counteract this toxicity in vivo. A team from the Chinese Academy of Medical Sciences at Peking Union Medical College, Beijing, China, have shown that cationic polyamidoamine dendrimers (PAMAMs) may cause severe acute lung injury in an in vivo murine model by triggering autophagic cell death, which is prevented by using specific autophagy inhibitors.
As the use of nanoparticles becomes more widespread, concerns are rapidly growing about the potential toxicity and environmental impact that nanoparticles may have, due to the fact that cationic particles have long been proven to cause lung toxicity. Carbon nanotubes have already been likened to asbestos owing to the mechanisms of severe lung injury that the particles can induce. The mechanisms of toxicity are unclear, and elucidation of these mechanisms may help to ensure effective treatment and prevention of any toxic side effects that these particles may cause.
In this study, cationic PAMAMs were shown to be toxic to human lung cell cultures and cause lung inflammation and death in mice. The scientists identified that the dendrimers deregulated the Akt–TSC2–mTOR signaling pathway, which leads to increased autophagy and cell death. This prompted them to see whether having identified the mechanism of the toxicity they could successfully counteract it. 3-methyladenine, an autophagy inhibitor, was co-administered with the nanoparticles, which prevented PAMAM-induced cell death in the human lung cells and significantly reduced lung damage in the murine model. This finding is very significant as it shows that potential nanoparticle toxicity could be counteracted simply with the co-administration of suitable preventative agents.
Dr Chengyu Jiang, one of the lead researchers of the study, commented on the siginifcance of the results: “Our study is the first to elucidate the molecular pathogenesis mechanism of some members of one class of nanoparticle, PAMAM, [and] how it causes acute lung injury”. He stressed how discovering the mechanism of the toxicity allowed them to look at potential ways to counteract any damage, and explore co-administration to help prevent toxicity. “Our study may help to set up standards for nanoparticle safety”, he added.
While these results are promising, research into nanoparticle toxicity has been limited to specific nanoparticles engineered for medical use. Studies are now needed for nanoparticles widely used in industry as Professor Ken Donaldson, Nanomedicine Editorial Board member and Professor of Respiratory Toxicology at Edinburgh University, UK, commented, “These PAMAM particles are from a class of highly specialized nanoparticles made by the drug industry in tiny amounts for delivery into the human body; by contrast, other nanoparticles are made industrially in tons for adding to paints or putting into hockey sticks. Clearly there is potential for workers and the public being accidentally exposed to the latter but not the former”.
With thanks to Dr C Jiang and Professor K Donaldson for their comments.
Source: Li C, Liu H, Sun Y et al.: PAMAM nanoparticles promote acute lung injury by inducing autophagic cell death through the Akt–TSC2–mTOR signaling pathway. J. Mol. Cell Biol. doi:10.1093/jmcb/mjp002 (2009 (Epub ahead of print).