One-pot synthesis of pH-responsive charge-switchable PEGylated nanoscale coordination polymers for improved cancer therapy.

Abstract

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 poly-histidine-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.

• Authors: Yu Yang, Ligeng Xu, Wenjun Zhu, Liangzhu Feng, Jingjing Liu, Qian Chen, Ziliang Dong, Jiayue Zhao, Zhuang Liu, Meiwan Chen
• Journal: Biomaterials (Biomaterials) Vol. 156 Pg. 121-133 (02 2018) ISSN: 1878-5905 [Electronic] Netherlands
• PMID: 29195181 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017. Published by Elsevier Ltd.

Chemical References

• Antineoplastic Agents
• Polyethylene Glycols

Topics

• Animals
• Antineoplastic Agents (pharmacology, therapeutic use)
• Cell Death (drug effects)
• Cell Line, Tumor
• Drug Liberation
• Endocytosis (drug effects)
• Hydrogen-Ion Concentration
• Mice, Inbred BALB C
• Nanoparticles (chemistry, ultrastructure)
• Nanotechnology (methods)
• Neoplasms (drug therapy, pathology)
• Optical Imaging
• Polyethylene Glycols (chemical synthesis, chemistry, pharmacokinetics)
• Tissue Distribution