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Targeted co-delivery of protein and drug to a tumor in vivo by sophisticated RGD-modified lipid-calcium carbonate nanoparticles

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Title: Targeted co-delivery of protein and drug to a tumor in vivo by sophisticated RGD-modified lipid-calcium carbonate nanoparticles
Authors: Peng, Jian Qing / Fumoto, Shintaro / Suga, Tadaharu / Miyamoto, Hirotaka / Kuroda, Naotaka / Kawakami, Shigeru / Nishida, Koyo
Issue Date: 28-Mar-2019
Publisher: Elsevier B.V.
Citation: Journal of Controlled Release, 302, pp.42-53; 2019
Abstract: Synchronized bio-distribution of combination therapies has several merits such as synergistic effects and reduced side-effects. Co-delivery of a protein and small molecule drug using a single nanocarrier is challenging because they possess totally different characteristics. Herein, we report the development of sophisticated nanoparticles composed of lipids, calcium carbonate and RGD peptide ligands for the co-delivery of a protein and small molecule drug combination via a simple preparation method. A ‘one-step’ ethanol injection method was employed to prepare the highly organized nanoparticles. The nanoparticles exhibited a spherical shape with ca. 130 nm diameter, and clearly had an integrated lipid layer covering the periphery. As a ligand, an RGD-modified lipid was post-inserted into the nanoparticles, which was important to overcome the ‘PEG dilemma’. The pH-sensitivity of the targeted nanoparticles contributed to the efficient intracellular co-delivery of a protein and drug combination in Colon26 tumor cells, and noticeably improved their accumulation in the tumor region of xenograft mice. Synchronized bio-distribution of the protein and drug was achieved, which was the foundation for the synergistic effects of the combination. The targeting capability of the nanoparticles along with their pH-sensitive drug release and the synchronized bio-distribution of their cargos led to the significant antitumor activity of the SOD and paclitaxel combination in mice. This study provides novel information for the design and preparation of functionalized nanoparticles for the delivery of a protein/drug combination in vivo.
Keywords: Superoxide dismutase / Paclitaxel / RGD peptide / Calcium carbonate / Lipid nanoparticles
URI: http://hdl.handle.net/10069/38944
ISSN: 01683659
DOI: 10.1016/j.jconrel.2019.03.021
Rights: ©2019, Elsevier. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
Type: Journal Article
Text Version: author
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/38944

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