Nanobiotechnology
Our laboratory is interested in how the integration of diagnosis and therapy might transform the lives of patients with cancer. In particular, we aim to exploit nanomaterials in our exploration of this paradigm. Already, the unique electromagnetic properties of nanomaterials have enabled significant advances in molecular detection, drug delivery, long term cellular tracking, and non-invasive imaging of disease in vivo.
We seek to engineer multifunctional nanoparticles by combining nanoparticle cores with nanoscale properties with bioresponsive functionalities. By integration of nanomaterials with our knowledge of the tumor microenvironment, we seek to develop nanoparticle conjugates that can be injected intravenously and that will: home to tumors, self-assemble to increase their local concentration, deliver chemotherapy locally, sense tumor activity/spread/recurrence, and allow physician intervention by remote actuation. We have focused on nanoparticle cores that harness features of the nanoscale- such as semiconductor quantum dots which exhibit size-based optical properties and dextran-coated iron oxide particles whose assembly alters the spin-spin relaxation (T2) of hydrogen protons on magnetic resonance imaging.
Figure 1. Multifunctional nanoparticle travels through blood stream to treat diseased tissue.
Collectively, we have explored the capabilities of these multifunctional nanoparticles by studies on targeting
[Akerman, pnas ; Simberg, pnas]
, triggered self-assembly
[Harris, angewandte; von Maltzahn, jacs],
remote actuation with RF fields
[Derfus. Advanced materials ],
sensing of kinase activity
[Min, advanced materials ],
and siRNA delivery
[Derfus, bioconj chem. ]
in models of breast and brain cancer. In these studies, we collaborate with Erkki Ruoslahti (Burnham Institute), M. Sailor (UCSD), Phil Sharp (MIT), and Charles Marcus (Harvard). Our long-term goals are to translate these novel technologies to patients. We anticipate that the resulting next generation therapeutics will be both multifunctional in that they are diagnostic and therapeutic, and modular in that they can be customized for different types of tumors and stages of tumor progression.
Figure 2. Triggered self-assembly of nanoparticles by tumor protease (MMP-2): produces change in T2 relaxivity detectable by magnetic resonance imaging. MMP2 cleaves protective polymer coating enabling assembly via complementary ligand binding. Angewandte Chemie, 2006
Our laboratory has also taken a leadership role in the emerging area of nanotoxicology- the study of toxicity of materials based on their size. We published one of the first studies examining the toxicity of cadmium-based semiconductor quantum dots and have now established a core facility open to PIs at MIT and Harvard to allow the rapid characterization of novel nanomaterials using standardized methods.