Jul 3, 2008
Non-invasive tracking of nanocarrier distribution in tumors
Nanocarrier-mediated chemotherapy has great promise in the treatment of cancer due to its ability to prolong the blood plasma half-life of the encapsulated chemotherapeutic and to selectively accumulate in tumors. However, in spite of important advances in the development of nano-chemotherapeutics, systemic chemotherapy is not the treatment of choice for malignant brain tumors, primarily due to the toxicity caused to non-tumor tissue. Therefore, novel techniques are required to understand and improve the drug availability at the tumor site while reducing harmful side effects. Nano-chemotherapeutics are able to accumulate at the tumor lesion due to the prolonged circulation of the nanocarrier and presence of abnormal leaky vasculature at the tumor site via the enhanced permeation and retention effect (EPR).
Nanocarrier-chemotherapeutic accumulation in the tumor is highly dependent on the degree of each individual tumor’s EPR. The tumor permeability not only differs between patients but also spatially within the same tumor. For this reason, the ability to visualize and monitor the extravasation and accumulation of the nanocarriers within the tumor will greatly aid in planning the optimal treatment regime for each patient, leading to personalized tumor therapy.
Researchers in the department of biomedical engineering at Georgia Tech/Emory demonstrated that nanocarriers can be tracked in vivo non-invasively. A 100 nm long circulating liposomal nanocarrier encapsulating gadodiamide introduced intravenously, induced strong T2-shortening in a 9.4 T MRI system. Nanocarrier accumulation in an orthotropic brain tumor was quantified by brain imaging after the nanocarriers were cleared from the blood circulation by the reticuloendothelial system. Adequate tumor dosing was achieved due to the long circulation half-life of the nanocarriers. Therefore, by optimizing nanocarrier properties such that it: a) can be non-invasively tracked in therapeutically safe doses; b) has a long circulation half-life to allow for tumor accumulation via leaky vasculature; and c) is cleared from circulation in 2–3 days enabled low-noise detection of tumor-accumulated nanocarriers. Such a system can be used to optimize tumor dosing of nanocarriers on a patient-to-patient basis, allowing for personalized tumor therapy.
About the author
Efstathios Karathanasis is a postdoctoral researcher at Georgia Tech who received his PhD from the University of Texas at Houston. Jae Kum is a research assistant professor at Georgia Tech/Emory University. Abhiruchi Agarwal is a PhD candidate in bioengineering at Georgia Tech. Vijal Patel was an undergraduate research assistant at Georgia Tech. Fuqiang Zhao was a research assistant professor at Georgia Tech/Emory University before he moved to Merck. Xiaoping Hu is professor of biomedical engineering and Georgia Research Alliance Imminent Scholar at Georgia Tech/Emory University. Ananth Anapragada is an associate professor in the school of health information sciences at the University of Texas at Houston. Ravi Bellamkonda is professor of biomedical engineering at Georgia Tech/Emory and a Georgia Cancer Coalition Distinguished Scholar.