Octa-arginine-modified pegylated liposomal doxorubicin: an effective treatment strategy for non-small cell lung cancer.
Cancer Lett
; 335(1): 191-200, 2013 Jul 10.
Article
em En
| MEDLINE
| ID: mdl-23419527
ABSTRACT
The present study aims to evaluate the efficacy of octa-arginine (R8)-modified pegylated liposomal doxorubicin (R8-PLD) for the treatment of non-small cell lung cancer, for which the primary treatment modality currently consists of surgery and radiotherapy. Cell-penetrating peptide R8 modification of Doxorubicin-(Dox)-loaded liposomes was performed by post-insertion of an R8-conjugated amphiphilic PEG-PE copolymer (R8-PEG-DOPE) into the liposomal lipid bilayer. In vitro analysis with the non-small cell lung cancer cell line, A549 confirmed the efficient cellular accumulation of Dox, delivered by R8-PLD compared to PLD. It led to the early initiation of apoptosis and a 9-fold higher level of the apoptotic regulator, caspase 3/7 (9.24±0.34) compared to PLD (1.07±0.19) at Dox concentration of 100 µg/mL. The treatment of A549 monolayers with R8-PLD increased the level of cell death marker lactate dehydrogenase (LDH) secretion (1.2±0.1 for PLD and 2.3±0.1 for R8-PLD at Dox concentration of 100 µg/mL) confirming higher cytotoxicity of R8-PLD than PLD, which was ineffective under the same treatment regimen (cell viability 90±6% in PLD vs. 45±2% in R8-PLD after 24h). R8-PLD had significantly higher penetration into the hypoxic A549 tumor spheroids compared to PLD. R8-PLD induced greater level of apoptosis to A549 tumor xenograft and dramatic inhibition of tumor volume and tumor weight reduction. The R8-PLD treated tumor lysate had a elevated caspase 3/7 expression than with R8-PLD treatment. This suggested system improved the delivery efficiency of Dox in selected model of cancer which supports the potential usefulness of R8-PLD in cancer treatment, lung cancer in particular.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doxorrubicina
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Carcinoma Pulmonar de Células não Pequenas
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Neoplasias Pulmonares
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Antineoplásicos
Limite:
Animals
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Humans
Idioma:
En
Revista:
Cancer Lett
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos