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A pH-Sensitive Nanocarrier for Tumor Targeting

Delivery of Ruthenium Complex for Tumor Theranostic by pH-Sensitive Nanocapsule

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Abstract

Purpose

Ruthenium complex is a potentially theranostic agent for cancer imaging and therapy, however its application is limited due to poor water-solubility and lack of tumor selectivity. To overcome the above drawbacks, pH-sensitive nanocapsule as a novel targeting carrier was designed to deliver ruthenium complex for treating xenograft tumor of mice.

Methods

The core/shell structured nanocapsule with ruthenium complex tris(1,10-phenanthroline) ruthenium(II) complex (3P-Ru) as the core and a pH-sensitive polymeric material poly (2-diisopropylaminoethyl methacrylate)-block poly(2-aminoethyl methacrylate hydrochloride) (PbPS) as the shell was synthesized and characterized. Meanwhile, the nanocapsule was used to investigate cell viability and evaluate tissue distribution as well as preventing tumor growth efficacy in U251 stem cells tumor-bearing mouse model.

Results

The nanocapsule had a size of 103.1 ± 11.3 nm, zeta potential of -40 ± 5.3 mV, EE of 76.7 ± 0.9%, LE of 25.4 ± 0.6% and it could control drug release under different pH conditions. The results of cell uptake showed that the fluorescent 3P-Ru loaded in the nanocapsule could be delivered into cells with high efficiency, and then significantly inhibited U251 proliferation in a concentration-dependent manner. After U251 stem cells were transplanted subcutaneously into mice, the 3P-Ru/PbPS nanocapsule (PbPS-Ru-NC) via intravenous administration could concentrate in tumor area and obviously prevent tumor growth.

Conclusions

The pH-sensitive nanocapsule as a antitumor agent carrier was able to effectively deliver 3P-Ru into gliomas cells, and cell growth was significantly inhibited both in vitro and in vivo. Such pH-sensitive nanocapsule for ruthenium complex delivery would have great potential application in tumor theranostics.

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Abbreviations

3P-Ru:

Tris(1,10-phenanthroline) ruthenium(II) complex

AFM:

Atomic force microscope

bFGF:

Basic fibroblast growth factor

DMEM-H:

Dulbecco’s Modified Eagle’s Medium (high glucose)

DMSO:

Dimethyl sulfoxide

EE:

Entrapment efficiency

EGF:

Epidermal growth factor

EPR:

Permeability and retention effect

FBS:

Fetal bovine serum

FITC:

Fluorescein isothiocyanate

LE:

Loading efficiency

MTT:

3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide

MWCO:

Molecular weight cut-off

NC:

Nanocapsule

PAMA/SA:

Succinic anhydride modified poly(2-aminoethyl methacrylate hydrochloride)

PbPS:

Poly (2-diisopropylaminoethyl methacrylate) -block poly(2-aminoethyl methacrylate hydrochloride)

PBS:

Phosphate-buffered saline

PDPA:

Poly(2-diisopropylaminoethyl methacrylate)

PEG:

1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPE-PEG2000-NHS)

SD:

Standard deviation

U251:

Human glioma cells

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ACKNOWLEDGMENTS & DISCLOSURES

This work was supported by grants from the Natural Science Foundation of China (81273416); the Scientific Research Foundation for Returned Scholars, Ministry of Education of China (2012-940), the Fundamental Research Funds for the Central Universities (XDJK2013A030); and the New Century Excellent Talents in University Award, Ministry of Education of China.

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Authors and Affiliations

  1. College of Pharmaceutical Sciences, Southwest University, Chongqing, 400715, China

    Ligang Chen, Chen Fu, Yajun Deng & Ailing Fu

  2. College of Polymer Science and Engineering, Sichuan University, Chengdu, 610065, China

    Wei Wu

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  1. Ligang Chen
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  2. Chen Fu
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  4. Wei Wu
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Correspondence to Ailing Fu.

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Chen, L., Fu, C., Deng, Y. et al. A pH-Sensitive Nanocarrier for Tumor Targeting. Pharm Res 33, 2989–2998 (2016). https://doi.org/10.1007/s11095-016-2021-2

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  • DOI: https://doi.org/10.1007/s11095-016-2021-2

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