Journal
ADVANCED HEALTHCARE MATERIALS
Volume 6, Issue 16, Pages -Publisher
WILEY
DOI: 10.1002/adhm.201700467
Keywords
nanoparticles; platinum prodrugs; polyphenols; self-assembly; tumor therapy
Funding
- Australian Research Council (ARC) Centre of Excellence in Convergent Bio-Nano Science and Technology [CE140100036]
- ARC under Australian Laureate Fellowship [FL120100030]
- Discovery Project schemes [DP130101846]
- National Health and Medical Research Council [APP1098867]
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Therapeutic nanoparticles hold clinical promise for cancer treatment by avoiding limitations of conventional pharmaceuticals. Herein, a facile and rapid method is introduced to assemble poly(ethylene glycol) (PEG)-modified Pt prodrug nanocomplexes through metal-polyphenol complexation and combined with emulsification, which results in approximate to 100 nm diameter nanoparticles (PtP NPs) that exhibit high drug loading (0.15 fg Pt per nanoparticle) and low fouling properties. The PtP NPs are characterized for potential use as cancer therapeutics. Mass cytometry is used to quantify uptake of the nanoparticles and the drug concentration in individual cells in vitro. The PtP NPs have long circulation times, with an elimination half-life of approximate to 18 h in healthy mice. The in vivo antitumor activity of the PtP NPs is systematically investigated in a human prostate cancer xenograft mouse model. Mice treated with the PtP NPs demonstrate four times better inhibition of tumor growth than either free prodrug or cisplatin. This study presents a promising strategy to prepare therapeutic nanoparticles for biomedical applications.
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