Integrated polymer nanotechnologies provide exciting new opportunities for multicomponent drug delivery to solid tumors. These strategies can maximize tumor-specific drug delivery and provide both spatial and temporal control over the release of compounds, leveraging optimal therapeutic synergy and minimizing off-target effects. Koch Institute researchers in the Hammond Lab are developing modular nanotechnology platforms for combinatorial RNA interference and cancer chemotherapy that incorporate colloidal drug carriers and multifunctional layer-by-layer (LbL) polymer assemblies. These constructs allow for the inhibition of currently un-druggable targets and recapitulate the optimal sequencing and timing of drug combinations screened in vitro. Herein, we present recent progress in engineering tumor-targeting stealth polymer multilayer components for these novel particle technologies that disassemble at hypoxic tumor pH. These multifunctional LbL components both stabilize and block non-specific adsorption, bind cell surface adhesion receptors associated with drug-resistant, tumor-initiating, and drug-resistant cellular phenotypes, and selectively erode at hypoxic tumor pH.

Hypoxia-induced disassembly and active tumor targeting of LbL nanoparticles

245th National Meeting (2013)

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