当前位置： SCI文献检索 > INTERNATIONAL JOURNAL OF PHARMACEUTICS期刊下所有文献 > Tissue slice model of human lung cancer to investigate telomerase inhibition by nanoparticle delivery of antisense 2'-O-methyl-RNA.

Tissue slice model of human lung cancer to investigate telomerase inhibition by nanoparticle delivery of antisense 2'-O-methyl-RNA.

Abstract：

:Nanoparticles delivery of oligonucleotides represents a potential approach for cancer treatment. However, most of the experiments were based on established cancer cell lines and may not reflect the original solid tumor in vivo. Both, tumor microenvironment and tumor cell biological properties in the tumor can influence the delivery efficiency of oligonucleotides. Therefore, it is important to understand the effect of nanoparticles delivery of oligonucleotides on tumor response in intact tissue architecture of individual tumors. We used freshly isolated human tumor tissue slices and primary lung cancer cells from non-small cell lung cancer patients to evaluate this nanocarrier system. Chitosan-coated poly(lactide-co-glycolide) (PLGA) nanoparticles were used to form oligonucleotide-nanoparticle-complexes (nanoplexes) with antisense 2'-O-methyl-RNA (OMR) that can inhibit telomerase activity by binding to the RNA component of telomerase. OMR cellular uptake was strongly enhanced by nanoplexes mediated delivery in both, primary cells and tissue slices. More than 80% of primary cancer cells and 50% of cells in tissue slices showed OMR uptake. Telomerase activity was inhibited by approximately 45% in primary cancer cells and about 40% in tissue slices. Nanoplexes could penetrate into tumor tissue without influencing tissue architecture and the delivered OMR was able to inhibit telomerase activity with relatively low cytotoxicity.

journal_name

Int J Pharm

journal_title

International journal of pharmaceutics

authors

Dong M,Philippi C,Loretz B,Nafee N,Schaefer UF,Friedel G,Ammon-Treiber S,Griese EU,Lehr CM,Klotz U,Mürdter TE

doi

10.1016/j.ijpharm.2011.07.009

subject

Has Abstract

pub_date

2011-10-31 00:00:00

pages

33-42

issue

1-2

eissn

0378-5173

issn

1873-3476

pii

S0378-5173(11)00638-7

journal_volume

419

pub_type

杂志文章

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