(5.1) Single walled carbon nanotubes for in vitro drug and gene delivery
We have uncovered that well functionalized single-walled nanotubes (SWNT) are non-toxic to cells and can be used as molecular transporters to shuttle various biological molecules including drugs, protein and short interfering RNA (siRNA) into cells via endocytosis. The molecular cargoes can be either covalently conjugated to nanotubes by cleavable bonds or non-covalently absorbed on the nanotube surface by hydrophobic and pi-pi stacking for delivery.
(5.2) In vivo behaviors and long term fate of carbon nanotubes
Encouraged by our success in the in vitro studies, we then investigate the in vivo behaviors of SWNTs with various collaborators in Stanford Medical School. It is found that well coated carbon nanotubes are non-toxic to mice as monitored over long periods of time. SWNTs after intravenously administrated into animals, are accumulated in the reticuloendothelial systems (RES) including liver and spleen, and slowly excreted primarily through biliary pathway ending in feces. Improved in vivo performance such as prolonged blood circulation, reduced RES uptake and accelerated clearance can be achieved by the optimization of nanotube surface chemistry, which is the key in our research.
(5.3) Preliminary efforts in cancer treatment by nanotechnology
We achieve efficient targeting of integrin αvβ3-positive U87MG human glioblastoma tumor with arginine-glycine-aspartic acid (RGD) peptide conjugated SWNTs. The high tumor uptake (~13%ID/g) is promising for drug delivery in cancer treatment. As a pilot effort towards therapeutic applications of carbon nanotubes, we conjugate paclitaxel (PTX), a commonly used chemotherapy drug, to branched PEG functionalized SWNTs via a cleavable ester bond. The SWNT-PTX conjugate is tested in mice with a breast cancer model, showing improved treatment efficacy over clinical PTX formulation based on cremophor (Taxol®).
As one-dimensional version of quantum dots, SWNTs have unique optical properties such as bright Raman scattering and near infrared (NIR) photoluminance, which can be used for biological imaging. In vivo molecular imaging of tumors using SWNTs as a photoacoustic contrast agent has also been explored in the collobaration with Prof. Sanjiv Gambhir.
Other graphitic nano-materials have also been developed in our laboratory for biological applications. We have synthesized FeCo nanocrystals shelled with a layer of graphene with excellent stability and outstanding magnetic properties suitable for MRI contrast agents. Our current work includes using this novel material for ultra-high resolution MRI imaging of angiogenesis. We are currently also comparing carbon based nanomaterials with Au nanoparticles, Au nanorods and semiconductor quantum dots for in vitro and in vivo biological applications.
