Enzyme responsive nanoassemblies have been of significant interest in drug delivery and biotechnology applications because an over expressed enzyme is directly related to the diseased state of a cell. Although there have been a number of reports of enzyme responsive nanoassemblies made up of amphiphilic building blocks such as block copolymers or dendrimers, one of the major drawbacks with these systems is that they show a very slow response. The reason for such slow response is due to the fact that the enzymatic substrate present in such assemblies are buried in their hydrophobic core which provides a poor accessibility to enzymes. To solve this problem, we used a self-immolative polymer capped with a phosphate group which is a good substrate for enzyme alkaline phosphatase and is hydrophilic in nature. When the polymer was treated with alkaline phosphatase, it degraded from head to tail through a domino effect mechanism. A hydrophobic modification of the polymer was used to make the polymer soluble in organic solvent. Furthermore, we used an oil in water emulsion methodology to formulate surfactant stabilized core shell particles with phosphate groups exposed on their surface. In the formulation process, Dichloromethane soluble polymer was used as the dispersed phase while water was used as a dispersion medium in presence of tween 80 as an emulsifier. The assemblies were characterized using dynamic light scattering (DLS), transmission electron microscopy (TEM) and NMR experiments. These assemblies could encapsulate hydrophobic dyes as model guest molecules. Upon treatment with enzymes, these core shell particles disassemble and release the encapsulated guest molecules at a rapid rate which was studied using UV-Vis and TEM experiments. The strategy mentioned in this study can have significant implications in the development of imaging and rapid drug delivery carriers for certain cancer cells where alkaline phosphatase is overexpressed.

Enzyme triggered rapid disassembly of polymeric nanoassemblies

2019 Fall National Meeting

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