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Encapsulating a Hydrophilic Chemotherapeutic into Rod-like Nanoparticles of a Genetically Encoded Asymmetric Triblock Polypeptide Improves its Efficacy

Value Proposition

Encapsulating hydrophilic chemotherapeutics into the core of polymeric nanoparticles can improve their therapeutic efficacy by their increasing plasma half-life, tumor accumulation and intracellular uptake, and by protecting them from premature degradation.

Technology

To achieve these goals, we designed 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. 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 (e.g., cisplatin) and imaging agents in vivo.

Advantages

  • Increased plasma half-life

  • Prevents premature degradation

  • Increased tumor accumulation and intracellular uptake

  • Lower chemo doses resulting in reduced side-effects

Duke File (IDF) Number

5023

Inventor(s)

  • Chilkoti, Ashutosh
  • Bhattacharyya, Jayanta

Publications

  • Bhattacharyya, J et al. Encapsulating a hydrophilic chemotherapeutic into rod-like nanoparticles of a genetically encoded asymmetric triblock polypeptide improves its efficacy. Advanced Functional Materials, Feb 2017

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College

Pratt School of Engineering

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