Journal
ADVANCED FUNCTIONAL MATERIALS
Volume 27, Issue 12, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adfm.201605421
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Funding
- National Institutes of Health [R01 EB000188, R01 EB007205]
- National Science Foundation [NSF-DGE-1106401]
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Encapsulating hydrophilic chemotherapeutics into the core of polymeric nanoparticles can improve their therapeutic efficacy by increasing their plasma half-life, tumor accumulation, and intracellular uptake, and by protecting them from premature degradation. To achieve these goals, a recombinant asymmetric triblock polypeptide (ATBP) that self-assembles into rod-shaped nanoparticles, and which can be used to conjugate diverse hydrophilic molecules, including chemotherapeutics, into their core is designed. These ATBPs consist of three segments: a biodegradable elastin-like polypeptide, a hydrophobic tyrosine-rich segment, and a short cysteine-rich segment, that spontaneously self-assemble into rod-shaped micelles. Covalent conjugation of a structurally diverse set of hydrophilic small molecules, including a hydrophilic chemotherapeutic-gemcitabine-to the cysteine residues also leads to formation of nanoparticles over a range of ATBP concentrations. Gemcitabine-loaded ATBP nanoparticles have significantly better tumor regression compared to free drug in a murine cancer model. This simple strategy of encapsulation of hydrophilic small molecules by conjugation to an ATBP can be used to effectively deliver a range of water-soluble drugs and imaging agents in vivo.
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