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Disregarded effect of biological fluids in siRNA delivery : human ascites fluid severely restricts cellular uptake of nanoparticles

George Dakwar (UGent) , Kevin Braeckmans (UGent) , Jo Demeester (UGent) , Wim Ceelen (UGent) , Stefaan De Smedt (UGent) and Katrien Remaut (UGent)
(2015) ACS APPLIED MATERIALS & INTERFACES. 7(43). p.24322-24329
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Center for nano- and biophotonics (NB-Photonics)
Abstract
Small interfering RNA (siRNA) offers a great potential for the treatment of various diseases and disorders. Nevertheless, inefficient in vivo siRNA delivery hampers its translation into the clinic. While numerous successful in vitro siRNA delivery stories exist in reduced-protein conditions, most studies so far overlook the influence of the biological fluids present in the in vivo environment. In this study, we compared the transfection efficiency of liposomal formulations in Opti-MEM (low protein content, routinely used for in vitro screening) and human undiluted ascites fluid obtained from a peritoneal carcinomatosis patient (high protein content, representing the in vivo situation). In Opti-MEM, all formulations are biologically active. In ascites fluid, however, the biological activity of all lipoplexes is lost except for lipofectamine RNAiMAX. The drop in transfection efficiency was not correlated to the physicochemical properties of the nanoparticles, such as premature siRNA release and aggregation of the nanoparticles in the human ascites fluid. Remarkably, however, all of the formulations except for lipofectamine RNAiMAX lost their ability to be taken up by cells following incubation in ascites fluid. To take into account the possible effects of a protein corona formed around the nanoparticles, we recommend always using undiluted biological fluids for the in vitro optimization of nanosized siRNA formulations next to conventional screening in low-protein content media. This should tighten the gap between in vitro and in vivo performance of nanoparticles and ensure the optimal selection of nanoparticles for further in vivo studies.
Keywords
liposomes, siRNA delivery, ascites, lipofectamine, peritoneal metastasis, protein corona, PROTEIN CORONA, PHYSIOLOGICAL ENVIRONMENT, BIOMOLECULE CORONA, RNA, INTERFERENCE, PARTICLES, SYSTEMS, CELLS

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Citation

Please use this url to cite or link to this publication:

Chicago
Dakwar, George, Kevin Braeckmans, Jo Demeester, Wim Ceelen, Stefaan De Smedt, and Katrien Remaut. 2015. “Disregarded Effect of Biological Fluids in siRNA Delivery : Human Ascites Fluid Severely Restricts Cellular Uptake of Nanoparticles.” Acs Applied Materials & Interfaces 7 (43): 24322–24329.
APA
Dakwar, G., Braeckmans, K., Demeester, J., Ceelen, W., De Smedt, S., & Remaut, K. (2015). Disregarded effect of biological fluids in siRNA delivery : human ascites fluid severely restricts cellular uptake of nanoparticles. ACS APPLIED MATERIALS & INTERFACES, 7(43), 24322–24329.
Vancouver
1.
Dakwar G, Braeckmans K, Demeester J, Ceelen W, De Smedt S, Remaut K. Disregarded effect of biological fluids in siRNA delivery : human ascites fluid severely restricts cellular uptake of nanoparticles. ACS APPLIED MATERIALS & INTERFACES. 2015;7(43):24322–9.
MLA
Dakwar, George, Kevin Braeckmans, Jo Demeester, et al. “Disregarded Effect of Biological Fluids in siRNA Delivery : Human Ascites Fluid Severely Restricts Cellular Uptake of Nanoparticles.” ACS APPLIED MATERIALS & INTERFACES 7.43 (2015): 24322–24329. Print.
@article{6989453,
  abstract     = {Small interfering RNA (siRNA) offers a great potential for the treatment of various diseases and disorders. Nevertheless, inefficient in vivo siRNA delivery hampers its translation into the clinic. While numerous successful in vitro siRNA delivery stories exist in reduced-protein conditions, most studies so far overlook the influence of the biological fluids present in the in vivo environment. In this study, we compared the transfection efficiency of liposomal formulations in Opti-MEM (low protein content, routinely used for in vitro screening) and human undiluted ascites fluid obtained from a peritoneal carcinomatosis patient (high protein content, representing the in vivo situation). In Opti-MEM, all formulations are biologically active. In ascites fluid, however, the biological activity of all lipoplexes is lost except for lipofectamine RNAiMAX. The drop in transfection efficiency was not correlated to the physicochemical properties of the nanoparticles, such as premature siRNA release and aggregation of the nanoparticles in the human ascites fluid. Remarkably, however, all of the formulations except for lipofectamine RNAiMAX lost their ability to be taken up by cells following incubation in ascites fluid. To take into account the possible effects of a protein corona formed around the nanoparticles, we recommend always using undiluted biological fluids for the in vitro optimization of nanosized siRNA formulations next to conventional screening in low-protein content media. This should tighten the gap between in vitro and in vivo performance of nanoparticles and ensure the optimal selection of nanoparticles for further in vivo studies.},
  author       = {Dakwar, George and Braeckmans, Kevin and Demeester, Jo and Ceelen, Wim and De Smedt, Stefaan and Remaut, Katrien},
  issn         = {1944-8244},
  journal      = {ACS APPLIED MATERIALS \& INTERFACES},
  keyword      = {liposomes,siRNA delivery,ascites,lipofectamine,peritoneal metastasis,protein corona,PROTEIN CORONA,PHYSIOLOGICAL ENVIRONMENT,BIOMOLECULE CORONA,RNA,INTERFERENCE,PARTICLES,SYSTEMS,CELLS},
  language     = {eng},
  number       = {43},
  pages        = {24322--24329},
  title        = {Disregarded effect of biological fluids in siRNA delivery : human ascites fluid severely restricts cellular uptake of nanoparticles},
  url          = {http://dx.doi.org/10.1021/acsami.5b08805},
  volume       = {7},
  year         = {2015},
}

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