Co-delivery of d-(KLAKLAK)2 peptide and doxorubicin using a pH-sensitive nanocarrier for synergistic anticancer treatment
- Authors
- Lim, C.; Won, W.R.; Moon, J.; Sim, T.; Shin, Y.; Kim, J.C.; Lee, E.S.; Youn, Y.S.; Oh, K.T.
- Issue Date
- Jul-2019
- Publisher
- Royal Society of Chemistry
- Citation
- Journal of Materials Chemistry B, v.7, no.27, pp 4299 - 4308
- Pages
- 10
- Journal Title
- Journal of Materials Chemistry B
- Volume
- 7
- Number
- 27
- Start Page
- 4299
- End Page
- 4308
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/33074
- DOI
- 10.1039/c9tb00741e
- ISSN
- 2050-7518
2050-750X
- Abstract
- Currently, one of the most important challenges in the development of nanotechnology-based anticancer treatments is the failure of nanoparticles to escape from the endo-lysosomal compartment and the resulting elimination of endocytosed nanoparticles via the exocytosis pathway without drug release. A pH-sensitive nanoparticle composed of poly(ethylene glycol)-poly(l-lysine)(-grafted 2,3 dimethyl maleic anhydride)-poly(lactic acid) triblock copolymer (PEG-PLL(-g-DMA)-PLA) with a pro-apoptotic peptide (d-(KLAKLAK)2) and an anticancer drug doxorubicin (Dox) (DTM(Pep, Dox)) was prepared and evaluated for its antiproliferative activity against tumor cells. Due to the membrane-lytic ability of the peptide and the proton sponge effect of the pH-sensitive nanocarrier, DTM(Pep, Dox) accelerated the disruption of the endo-lysosomal membrane and displayed enhanced anticancer activities, arising from strong synergism, under in vitro and in vivo conditions. The prepared formulations are anticipated to be of potential use in nanotechnology-based combination therapy and it is believed that this novel formulation will have new applications in advanced tumor therapy. © 2019 The Royal Society of Chemistry.
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