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Multifunctional probes for simultaneous magnetic resonance imaging (MRI) and drug delivery have attracted considerable interest due to their promising potential applications in the early-stage diagnosis and therapy of the diseases. In this study, hollow manganese phosphate nanoparticles (HMP NPs) with an average diameter of 18 nm were synthesized and aminated through silanization, which enabled the covalent conjugation of biocompatible poly(ethylene glycol) (PEG) on their surfaces. The anti-tumor drug doxorubicin (DOX) could be loaded into the hollow cavities. Under physiological conditions (pH 7.4), the NPs showed low MRI T1 contrast (r1 = 1.19 L·mmol-1·s-1), whereas high T1 enhancement (r1 = 5.22 L·mmol-1·s-1) was achieved after dissolving them in endosome/lysosome mimetic conditions (pH 5.4). This is due to the fact that the NPs were easily eroded, which resulted in the release of Mn2+ at low pH. To use this interesting phenomenon for targeted DOX drug delivery, we conjugated the tumor-targeting ligand folic acid (FA) on HMP NPs and investigated their drug delivery capacity and cytotoxicity to cell lines expressing different amount of folate receptor (FR). KB cells showed more significant cellular uptake than HeLa cells and A549 cells, as confirmed by confocal laser scanning microscopy (CLSM), flow cytometry and cellular T1-weighted MRI. Furthermore, the drug-loaded HMP NPs exhibited greater cytotoxicity to KB cells. Our results suggest that functionalized HMP NPs can act as an effective multifunctional probe for selective diagnosis with MRI, as well as giving efficient targeted drug delivery.


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Hollow Manganese Phosphate Nanoparticles as Smart Multifunctional Probes for Cancer Cell Targeted Magnetic Resonance Imaging and Drug Delivery

Show Author's information Jing Yu1Rui Hao1Fugeng Sheng2( )Lili Xu2Gongjie Li2Yanglong Hou1( )
Department of Materials Science and EngineeringCollege of EngineeringPeking UniversityBeijing100871China
Department of RadiologyAffiliated Hospital of the Academy of Military Medical SciencesBeijing100071China

Abstract

Multifunctional probes for simultaneous magnetic resonance imaging (MRI) and drug delivery have attracted considerable interest due to their promising potential applications in the early-stage diagnosis and therapy of the diseases. In this study, hollow manganese phosphate nanoparticles (HMP NPs) with an average diameter of 18 nm were synthesized and aminated through silanization, which enabled the covalent conjugation of biocompatible poly(ethylene glycol) (PEG) on their surfaces. The anti-tumor drug doxorubicin (DOX) could be loaded into the hollow cavities. Under physiological conditions (pH 7.4), the NPs showed low MRI T1 contrast (r1 = 1.19 L·mmol-1·s-1), whereas high T1 enhancement (r1 = 5.22 L·mmol-1·s-1) was achieved after dissolving them in endosome/lysosome mimetic conditions (pH 5.4). This is due to the fact that the NPs were easily eroded, which resulted in the release of Mn2+ at low pH. To use this interesting phenomenon for targeted DOX drug delivery, we conjugated the tumor-targeting ligand folic acid (FA) on HMP NPs and investigated their drug delivery capacity and cytotoxicity to cell lines expressing different amount of folate receptor (FR). KB cells showed more significant cellular uptake than HeLa cells and A549 cells, as confirmed by confocal laser scanning microscopy (CLSM), flow cytometry and cellular T1-weighted MRI. Furthermore, the drug-loaded HMP NPs exhibited greater cytotoxicity to KB cells. Our results suggest that functionalized HMP NPs can act as an effective multifunctional probe for selective diagnosis with MRI, as well as giving efficient targeted drug delivery.

Keywords: magnetic resonance imaging (MRI), targeted drug delivery, Manganese phosphate, molecular probe

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Publication history
Copyright
Acknowledgements

Publication history

Received: 24 May 2012
Revised: 18 July 2012
Accepted: 13 August 2012
Published: 07 September 2012
Issue date: October 2012

Copyright

© Tsinghua University Press and Springer-Verlag Berlin Heidelberg 2012

Acknowledgements

Acknowledgements

This work was supported in part by National Natural Science Foundation of China (NSFC) (Nos. 51125001, 51172005, 90922033, and 21105120), the National Basic Research Program of China (No. 2010CB934601), the Doctoral Program (No. 20090001120010) and New Century Talent of the Education Ministry of China (No. NCET-09-0177), the Fok Ying Tung Education Foundation (No. 122043), and the New Star Program of Beijing Municipal Science and Technology Commission (BCST) (No. 2008B02).

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