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

Publication ,  Journal Article
Bhattacharyya, J; Weitzhandler, I; Ho, SB; McDaniel, JR; Li, X; Tang, L; Liu, J; Dewhirst, M; Chilkoti, A
Published in: Adv Funct Mater
March 24, 2017

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, 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 and imaging agents in vivo.

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Published In

Adv Funct Mater

DOI

ISSN

1616-301X

Publication Date

March 24, 2017

Volume

27

Issue

12

Location

Germany

Related Subject Headings

  • Materials
  • 51 Physical sciences
  • 40 Engineering
  • 34 Chemical sciences
  • 09 Engineering
  • 03 Chemical Sciences
  • 02 Physical Sciences
 

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Bhattacharyya, J., Weitzhandler, I., Ho, S. B., McDaniel, J. R., Li, X., Tang, L., … Chilkoti, A. (2017). Encapsulating a Hydrophilic Chemotherapeutic into Rod-like Nanoparticles of a Genetically Encoded Asymmetric Triblock Polypeptide Improves its Efficacy. Adv Funct Mater, 27(12). https://doi.org/10.1002/adfm.201605421
Bhattacharyya, Jayanta, Isaac Weitzhandler, Shihan Bryan Ho, Jonathan R. McDaniel, Xinghai Li, Lei Tang, Jinyao Liu, Mark Dewhirst, and Ashutosh Chilkoti. “Encapsulating a Hydrophilic Chemotherapeutic into Rod-like Nanoparticles of a Genetically Encoded Asymmetric Triblock Polypeptide Improves its Efficacy.Adv Funct Mater 27, no. 12 (March 24, 2017). https://doi.org/10.1002/adfm.201605421.
Bhattacharyya J, Weitzhandler I, Ho SB, McDaniel JR, Li X, Tang L, et al. Encapsulating a Hydrophilic Chemotherapeutic into Rod-like Nanoparticles of a Genetically Encoded Asymmetric Triblock Polypeptide Improves its Efficacy. Adv Funct Mater. 2017 Mar 24;27(12).
Bhattacharyya, Jayanta, et al. “Encapsulating a Hydrophilic Chemotherapeutic into Rod-like Nanoparticles of a Genetically Encoded Asymmetric Triblock Polypeptide Improves its Efficacy.Adv Funct Mater, vol. 27, no. 12, Mar. 2017. Pubmed, doi:10.1002/adfm.201605421.
Bhattacharyya J, Weitzhandler I, Ho SB, McDaniel JR, Li X, Tang L, Liu J, Dewhirst M, Chilkoti A. Encapsulating a Hydrophilic Chemotherapeutic into Rod-like Nanoparticles of a Genetically Encoded Asymmetric Triblock Polypeptide Improves its Efficacy. Adv Funct Mater. 2017 Mar 24;27(12).
Journal cover image

Published In

Adv Funct Mater

DOI

ISSN

1616-301X

Publication Date

March 24, 2017

Volume

27

Issue

12

Location

Germany

Related Subject Headings

  • Materials
  • 51 Physical sciences
  • 40 Engineering
  • 34 Chemical sciences
  • 09 Engineering
  • 03 Chemical Sciences
  • 02 Physical Sciences