TY - JOUR
T1 - Improved anti-tumoral therapeutic efficacy of 4-hydroxynonenal incorporated in novel lipid nanocapsules in 2D and 3D models
AU - Pizzimenti, Stefania
AU - Daga, Martina
AU - Ciamporcero, Eric
AU - Toaldo, Cristina
AU - Pettazzoni, Piergiorgio
AU - Osella-Abate, Simona
AU - Novelli, Mauro
AU - Minelli, Rosalba
AU - Bisazza, Agnese
AU - Gamba, Paola
AU - Testa, Gabriella
AU - Ullio, Chiara
AU - Ferruti, Paolo
AU - Ranucci, Elisabetta
AU - Bernengo, Maria Grazia
AU - Ferretti, Carlo
AU - Dianzani, Chiara
AU - Biasi, Fiorella
AU - Barrera, Giuseppina
AU - Cavalli, Roberta
N1 - Publisher Copyright:
Copyright © 2015 American Scientific Publishers. All rights reserved.
PY - 2015/12/1
Y1 - 2015/12/1
N2 - 4-hydroxynonenal (HNE), a lipid peroxidation product, is a promising anti-neoplastic drug due to its remarkable anti-cancer activities. However, this possibility has not been explored, because the delivery of HNE is very challenging as a result of its low solubility and its poor stability. This study intentionally designed a new type of lipid nanocapsules specifically for HNE delivery. They consist of a medium chain triglyceride liquid oil core surrounded by a polymer shell. A β-cyclodextrin-poly(4-acryloylmorpholine) conjugate was selected as the shell component. HNE-loaded nanocapsules were about 350 nm in size with a negative surface charge. They were stable for two years when stored in suspensions at 4 °C. In vitro experiments showed that HNE was released from the nanocapsules at a considerable rate. Nanocapsule uptake into cells was evaluated using a fluorescent formulation that revealed rapid internalisation. Cytotoxicity studies demonstrated the safety of the formulation. Enhanced anti-tumoral activity against various cell lines, depending on increased HNE stability, was obtained by using HNE-loaded nanocapsules. In particular, we have demonstrated an increase in anti-proliferative, pro-apoptotic and differentiative activity in several tumour cell lines from different tissues. Moreover, we evaluated the effects of these new nanocapsules on a three-dimensional human reconstructed model of skin melanoma. Interestingly, the encouraging results obtained with topical administration on the epidermal surface could open new perspectives in melanoma treatments.
AB - 4-hydroxynonenal (HNE), a lipid peroxidation product, is a promising anti-neoplastic drug due to its remarkable anti-cancer activities. However, this possibility has not been explored, because the delivery of HNE is very challenging as a result of its low solubility and its poor stability. This study intentionally designed a new type of lipid nanocapsules specifically for HNE delivery. They consist of a medium chain triglyceride liquid oil core surrounded by a polymer shell. A β-cyclodextrin-poly(4-acryloylmorpholine) conjugate was selected as the shell component. HNE-loaded nanocapsules were about 350 nm in size with a negative surface charge. They were stable for two years when stored in suspensions at 4 °C. In vitro experiments showed that HNE was released from the nanocapsules at a considerable rate. Nanocapsule uptake into cells was evaluated using a fluorescent formulation that revealed rapid internalisation. Cytotoxicity studies demonstrated the safety of the formulation. Enhanced anti-tumoral activity against various cell lines, depending on increased HNE stability, was obtained by using HNE-loaded nanocapsules. In particular, we have demonstrated an increase in anti-proliferative, pro-apoptotic and differentiative activity in several tumour cell lines from different tissues. Moreover, we evaluated the effects of these new nanocapsules on a three-dimensional human reconstructed model of skin melanoma. Interestingly, the encouraging results obtained with topical administration on the epidermal surface could open new perspectives in melanoma treatments.
KW - 4-hydroxynonenal
KW - Human melanoma model
KW - Lipid nanocapsules
KW - Lipid peroxidation
KW - Prolonged release
KW - Tumour cell lines
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UR - http://www.scopus.com/inward/citedby.url?scp=84953344638&partnerID=8YFLogxK
U2 - 10.1166/jbn.2015.2131
DO - 10.1166/jbn.2015.2131
M3 - Article
C2 - 26510311
AN - SCOPUS:84953344638
SN - 1550-7033
VL - 11
SP - 2169
EP - 2185
JO - Journal of biomedical nanotechnology
JF - Journal of biomedical nanotechnology
IS - 12
ER -