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

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

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Hoon Choi, Ting Liu, Kavindra Nath, Rong Zhou, I. Wei Chen
Elsevier BV
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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