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Article Dans Une Revue Cancer Letters Année : 2013

Octa-arginine-modified pegylated liposomal doxorubicin: An effective treatment strategy for non-small cell lung cancer

Résumé

The present study aims to evaluate the efficacy of octa-arginine (R8)-modified pegylated liposomal doxo-rubicin (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 lg/mL. The treatment of A549 monolayers with R8-PLD increased the level of cell death marker lactate dehydroge-nase (LDH) secretion (1.2 ± 0.1 for PLD and 2.3 ± 0.1 for R8-PLD at Dox concentration of 100 lg/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 24 h). 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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hal-02995795 , version 1 (09-12-2020)

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Swati Biswas, Pranali P Deshpande, Federico Perche, Namita S Dodwadkar, Shailendra D Sane, et al.. Octa-arginine-modified pegylated liposomal doxorubicin: An effective treatment strategy for non-small cell lung cancer. Cancer Letters, 2013, 335 (1), pp.191 - 200. ⟨10.1016/j.canlet.2013.02.020⟩. ⟨hal-02995795⟩
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