TY - JOUR
T1 - Biocompatibility study of two diblock copolymeric nanoparticles for biomedical applications by in vitro toxicity testing
AU - Goñi-de-Cerio, Felipe
AU - Mariani, Valentina
AU - Cohen, Dror
AU - Madi, Lea
AU - Thevenot, Julie
AU - Oliveira, Hugo
AU - Uboldi, Chiara
AU - Giudetti, Guido
AU - Coradeghini, Rosella
AU - Garanger, Elisabeth
AU - Rossi, François
AU - Portugal-Cohen, Meital
AU - Oron, Miriam
AU - Korenstein, Rafi
AU - Lecommandoux, Sébastien
AU - Ponti, Jessica
AU - Suárez-Merino, Blanca
AU - Heredia, Pedro
N1 - Funding Information:
Acknowledgments This study was supported by the European Commission FP7 Programme 2007–2013 under NANOTHER project (www.nanother.eu), Grant Agreement Number CP-IP 213631-2 NANOTHER. We want to particularly acknowledge the patients enrolled in the blood serum study for their participation and the Basque Biobank for Research-OEHUN for its collaboration.
PY - 2013/11
Y1 - 2013/11
N2 - Drugs used for chemotherapy normally carry out adverse, undesired effects. Nanotechnology brings about new horizons to tackle cancer disease with a different strategy. One of the most promising approaches is the use of nanocarriers to transport active drugs. These nanocarriers need to have special properties to avoid immune responses and toxicity, and it is critical to study these effects. Nanocarriers may have different nature, but polypeptide-based copolymers have attracted considerable attention for their biocompatibility, controlled and slow biodegradability as well as low toxicity. Little has been done regarding specific nanocarriers toxicity. In this study, we performed a thorough toxicological study of two different block copolymer nanoparticles (NPs); poly(trimethylene carbonate)-block-poly(L-glutamic acid) (PTMC- b-PGA) and poly(ethylene glycol)-block-poly(γ-benzyl-L-glutamate) (PEG-b-PBLG) with sizes between 113 and 131 nm. Low blood-serum-protein interaction was observed. Moreover, general toxicity assays and other endpoints (apoptosis or necrosis) showed good biocompatibility for both NPs. Reactive oxygen species increased in only two cell lines (HepG2 and TK6) in the presence of PTMCb-PGA. Cytokine production study showed cytokine induction only in one cell line (A549). We also performed the same assays on human skin organ culture before and after UVB light treatment, with a moderate toxicity after treatment independent of NPs presence or absence. Interleukin 1 induction was also observed due to the combined effect of PEG-b-PBLG and UVB light irradiation. Future in vivo studies for biocompatibility and toxicity will provide more valuable information, but, so far, the findings presented here suggest the possibility of using these two NPs as nanocarriers for nanomedical applications, always taking into account the application procedure and the way in which they are implemented.
AB - Drugs used for chemotherapy normally carry out adverse, undesired effects. Nanotechnology brings about new horizons to tackle cancer disease with a different strategy. One of the most promising approaches is the use of nanocarriers to transport active drugs. These nanocarriers need to have special properties to avoid immune responses and toxicity, and it is critical to study these effects. Nanocarriers may have different nature, but polypeptide-based copolymers have attracted considerable attention for their biocompatibility, controlled and slow biodegradability as well as low toxicity. Little has been done regarding specific nanocarriers toxicity. In this study, we performed a thorough toxicological study of two different block copolymer nanoparticles (NPs); poly(trimethylene carbonate)-block-poly(L-glutamic acid) (PTMC- b-PGA) and poly(ethylene glycol)-block-poly(γ-benzyl-L-glutamate) (PEG-b-PBLG) with sizes between 113 and 131 nm. Low blood-serum-protein interaction was observed. Moreover, general toxicity assays and other endpoints (apoptosis or necrosis) showed good biocompatibility for both NPs. Reactive oxygen species increased in only two cell lines (HepG2 and TK6) in the presence of PTMCb-PGA. Cytokine production study showed cytokine induction only in one cell line (A549). We also performed the same assays on human skin organ culture before and after UVB light treatment, with a moderate toxicity after treatment independent of NPs presence or absence. Interleukin 1 induction was also observed due to the combined effect of PEG-b-PBLG and UVB light irradiation. Future in vivo studies for biocompatibility and toxicity will provide more valuable information, but, so far, the findings presented here suggest the possibility of using these two NPs as nanocarriers for nanomedical applications, always taking into account the application procedure and the way in which they are implemented.
KW - Amphiphilic copolymers
KW - Biomedicine
KW - Cancer therapy
KW - In vitro toxicity
KW - Nanoparticles
KW - Nanoparticles toxicity
UR - http://www.scopus.com/inward/record.url?scp=84892639710&partnerID=8YFLogxK
U2 - 10.1007/s11051-013-2036-0
DO - 10.1007/s11051-013-2036-0
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AN - SCOPUS:84892639710
SN - 1388-0764
VL - 15
JO - Journal of Nanoparticle Research
JF - Journal of Nanoparticle Research
IS - 11
ER -