Poly-l-lysine assisted synthesis of core-shell nanoparticles and conjugation with triphenylphosphonium to target mitochondria

In this paper, we report a facile route to synthesize mitochondria-targeted core-shell nanoparticles (NPs). Firstly, PLL-coated NPs are prepared by a one-step reprecipitation-encapsulation method assisted by positively charged poly-l-lysine (PLL). The effect of the molecular weight of PLL on the for...

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Bibliographic Details
Published in:Journal of materials chemistry. B, Materials for biology and medicine Materials for biology and medicine, 2013-10, Vol.1 (38), p.5143-5152
Main Authors: Wang, Xiao-Hui, Peng, Hong-Shang, Yang, Lin, You, Fang-Tian, Teng, Feng, Tang, Ai-Wei, Zhang, Fu-Jun, Li, Xiao-Hua
Format: Article
Language:English
Subjects:
Cellular
Conjugation
Imaging
Mitochondria
Nanoparticles
Nanostructure
Sag
Zeta potential
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Summary:In this paper, we report a facile route to synthesize mitochondria-targeted core-shell nanoparticles (NPs). Firstly, PLL-coated NPs are prepared by a one-step reprecipitation-encapsulation method assisted by positively charged poly-l-lysine (PLL). The effect of the molecular weight of PLL on the formation of particles is studied in terms of morphology, size and zeta potential, and medium-sized PLL (MH-PLL) is proved to be the optimum one. By means of crosslinking with different amounts of glutaraldehyde, amino groups in MH-PLL-NPs are characterized by zeta potential and fluorescamine assay, respectively. The results indicate that in the PLL shell, only a small portion of amino groups (surface amino groups, SAGs) are available for conjugation, while the other groups exclusively contribute to zeta potential. Subsequently, a known mitochondriotropic ligand, triphenylphosphonium (TPP), is conjugated with SAG via a carbodiimide reaction, which is evaluated by NMR and absorption spectra, respectively. The TPP-MH-PLL-NPs exhibit a low cytotoxic effect tested by the MTT method, as well as efficient cellular uptake microscopically observed after a fluorescent dye, coumarin 6, is incorporated. Most importantly, the TPP-conjugated NPs can selectively target mitochondria, demonstrated by the merged z-stacked images in co-localization experiments with MitoTracker-stained mitochondria. Given that many hydrophobic species could be loaded into the particle core, TPP-MH-PLL-NPs are very promising as mitochondria-targeted nanocarriers for imaging or anti-cancer therapies.
ISSN:2050-750X
2050-7518
DOI:10.1039/c3tb20884b