Host: Pat Stayton, Dept of Bioengineering
Versatile surface modification of nanoparticles for drug delivery
Effective delivery of nanoparticles (NPs) relies on appropriate strategies to prevent, or at least to reduce, the interactions between NPs and undesirable blood/tissue components encountered en route to target tissues. When this requirement is not met, NPs are prematurely cleared or undergo irreversible changes in size and structure, losing the potential to carry bioactive payloads to target tissues. Surface modification with polyethylene glycol (PEG) is the most commonly used method to prevent such problems; however, it involves several limitations, such as interference with cellular uptake and endosomal escape of NPs. The use of tumor-specific ligands enhances cellular uptake and retention of NPs at tumors; however, their presence often compromises the ability of NPs to avoid immune surveillance during circulation. My laboratory develops various strategies to modify polymeric NP surfaces, with an aim to minimize undesirable interactions between NPs and blood/tissue components without compromising their ability to deliver drug to target tissues. This effort includes encapsulation of NPs in osmotically active microparticles, surface modification of NPs with low molecular weight chitosan or chitosan derivative, and dual functionalization with a cell-interactive peptide and a PEG-enzyme-susceptible peptide conjugate. The surface modification is facilitated by the use of dopamine polymerization method, applicable to a wide variety of substrates and functional ligands.