Journal
BIOMATERIALS
Volume 156, Issue -, Pages 121-133Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2017.11.038
Keywords
Nanoscale coordination polymers (NCPs); One-pot synthesis; Carrier-free drug delivery system; pH-responsive charge-switching; Chemotherapy
Funding
- Ministry of Science and Technology (MOST) of China [2016YFA0201200]
- National Natural Science Foundation of China [51525203, 81403120]
- Collaborative Innovation Center of Suzhou Nano Science and Technology
- Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions
- Macao Science and Technology Development Fund [096/2015/A3]
- Research Fund of the University of Macau [MYRG2016-00130-ICMS- QRCM]
Ask authors/readers for more resources
Nanoscale coordination polymers (NCPs) are promising nanomedicine platforms featured with biodegradability and versatile functionalities. However, multi-step post-synthesis surface modification is usually required to functionalize as-made NCPs before their biomedical applications. Moreover, efforts are still required to design therapeutic NCPs responsive to the unique tumor microenvironment to achieve more specific and effective therapy. Herein, we uncover a simple yet general strategy to synthesize a series of polyethylene glycol (PEG) modified NCPs via a one-step method by adding polyhistidine-PEG co-polymer into the mixture of metal ions and organic ligands during NCPs formation. With NCPs consisting Ca2+/dicarboxylic cisplatin (IV) prodrug as the example, we show that such Ca/Pt(IV)@pHis-PEG NCPs are highly sensitive to pH changes. With slightly negative charges and compact structure under pH 7.4 during blood circulation, those NCPs exhibit efficient passive accumulation in the tumor, in which the reduced pH (c.a. 6.5) would trigger charge conversion and size expansion to enhance their tumor retention and cell internationalization. After cellular uptake, NCPs within cell endo-/lysosomes with further reduced pH would then lead to decomposition of those NCPs and thus drug release. Chemotherapy with Ca/Pt(IV)@pHis-PEG NCPs in our animal tumor model demonstrates great efficacy under low drug doses, and is found to be particularly effective towards solid tumors with reduced pH. (C) 2017 Published by Elsevier Ltd.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available