Peptide nanoparticle with pH-sensing cargo solubility enhances cancer drug efficiency

Citation data:

Nano Today, ISSN: 1748-0132, Vol: 13, Page: 15-22

Publication Year:
2017
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DOI:
10.1016/j.nantod.2017.02.008
Author(s):
Hoon Choi, Ting Liu, Kavindra Nath, Rong Zhou, I. Wei Chen
Publisher(s):
Elsevier BV
Tags:
Biochemistry, Genetics and Molecular Biology, Medicine, Chemical Engineering, Engineering, Materials Science, Pharmacology, Toxicology and Pharmaceutics
article description
We report a class of 17-amino-acid peptides that undergo a sharp hydrophobicity transition at pH around 7. Nanoparticles made of such peptides exhibit ultra pH-sensitivity and autonomous drug-eluting properties, which are beneficial for cancer drug delivery. At pH above 7, the peptides bind water-insoluble drug cargo and form a nanoparticle that protects its cargo from serum proteins. Sensing tumor's mildly acidic pH (≤7.0), nanoparticle peptides undergo a hydrophobic-to-hydrophilic transition and release drug molecules in the interstitial fluid as the nanoparticle migrates down the pH gradient in the tumor. When this pH-sensing and drug-eluting nanoparticle formulation was used to deliver two drugs, lonidamine inhibiting tumor bioenergetics and bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide (BPTES) targeting cancer glutamine metabolism, to triple negative human breast cancer xenografts, the nanoparticle drug demonstrated superior efficiency compared to the respective standard formulation.

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