Our Science – Blumenthal Website
Robert Blumenthal, Ph.D.
Multifunctional Nanoparticles for Targeted and Triggered Delivery of Therapeutics
The design of multifunctional nanoparticles that deliver their payload into specific organelles and cell interiors is one of the main challenges facing nanotechnologists involved in nanomedicine. Nanoparticles are extensively being employed to preferentially concentrate drugs and therapeutic agents in tumor sites. This tumor-targeting strategy known as enhanced permeation and retention (EPR) has first been used in the clinic for particle-mediated delivery by liposomes. Our research focuses on the architecture, composition and function of cell membrane that acts as the frontier between the cell and its environment. The cell/plasma membrane encompasses a lipid-based sheath that encloses the cytoplasm, and creates a selectively permeable barrier. These lipid bilayers are thin, flexible self-sealing boundaries that are used by cells to create regions of different composition and electrochemical potential. The lipid bilayers also bear glycoconjugates interspersed with proteins, which serve as gatekeepers to regulate active and passive transport of molecules essential for cellular functions. The living cell must retain molecules, such as DNA, RNA, and its variety of proteins from dissipating away, while keeping out foreign molecules that might damage or destroy the cell's contents, including molecules essential for life. Our task as cancer nanotechnologists is to find clever ways of selectively destroying diseased (cancer) cells while leaving normal cells intact. Our approach is to design lipid-based nanoparticles (such as liposomes) to specifically target and deliver drugs/genes to tumor cells.
Photo-induced Chemical Reactions in the Membrane: Applications to Vaccine Development and Chemotherapy
We are developing a new chemical nanobiology that involves reaction of photo-activable probes within a membrane, which serves as a 50 nm, highly organized hydrophobic container. We have used the membrane bilayer specific probe iodonaphthylazide (INA) that reacts with proteins and lipids following activation in situ either by direct UV irradiation or by energy transfer from a variety of donor chromophores. We have used this method in an analytic model to establish which proteins of the viral envelope penetrate the target cell membrane in the course of infection. The covalent modification of membrane proteins and lipids also modifies the function of membrane proteins. When applied to enveloped viruses, the treatment resulted in a complete loss of infectivity due to a loss of function of viral fusion proteins. We have shown the wide applicability of this inactivation technique to HIV, Influenza, Ebola, Marburg, Dengue and VEE viruses. By exclusively targeting the lipidic domain, exposed epitopes are preserved making the inactivated pathogens excellent vaccine candidates potentially applicable to cancer vaccines. When applied to whole cells the treatment resulted in loss of signaling function of cell surface receptors and loss of transport function of multi drug resistance transporters. Overall, photo-activation of INA in various cell lines, including those over-expressing the multi-drug resistance transporters leads to apoptosis. We are developing this new modality for cancer treatment using small hydrophobic molecules that can be turned into tumor killing toxic compounds by targeted radiation and ultrasound.
This page was last updated on 2/19/2013.