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A pH-Sensitive Nanocarrier for Tumor Targeting : Delivery of Ruthenium Complex for Tumor Theranostic by pH-Sensitive Nanocapsule.

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.

journal_name

Pharm Res

journal_title

Pharmaceutical research

authors

Chen L,Fu C,Deng Y,Wu W,Fu A

doi

10.1007/s11095-016-2021-2

subject

Has Abstract

pub_date

2016-12-01 00:00:00

pages

2989-2998

issue

eissn

0724-8741

issn

1573-904X

pii

10.1007/s11095-016-2021-2

journal_volume

pub_type

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A pH-Sensitive Nanocarrier for Tumor Targeting : Delivery of Ruthenium Complex for Tumor Theranostic by pH-Sensitive Nanocapsule.