Biotransporting Self-Assembled Nanofactories Using Polymer Vesicles with Molecular Permeability for Enzyme Prodrug Cancer Therapy.

Abstract

As "biotransporting nanofactories", in vivo therapeutic biocatalyst nanoreactors would enable encapsulated enzymes to transform inert prodrugs or neutralize toxic compounds at target disease sites. This would offer outstanding potential for next-generation therapeutic platforms, such as enzyme prodrug therapy. Designing such advanced materials has, however, proven challenging. Here, it is shown that self-assembled nanofactories formulate with polymeric vesicles with an intrinsically permeable membrane. The vesicles, CAPsomes, are composed of carbohydrate-b-poly(propylene glycol) and show molecular-weight-depended permeability. This property enables CAPsomes to act as biocatalyst nanoreactors, protecting encapsulated enzymes from degradation while acting on low-molecular-weight substrates. In tumor bearing mice, combined treatment with enzyme-loaded CAPsomes and doxorubicin prodrug inhibit tumor growth in these mice without any observable toxicity. The results demonstrate, for the first time, in vivo therapeutic efficacy of CAPsomes as nanofactories for enzyme prodrug cancer therapy.