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Biography |
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CAREER HISTORY : Professor Benoit acquired a solid foundation in the domain of micro and nanoencapsulation. At the School of Pharmacy of Angers, he is teaching Pharmaceutics. In parallel, he created in 2001 a highly competitive research group at the international level, Mint (INSERM/CNRS), that he headed up until 2017.
He was recognized as an AAPS Fellow in 1994. He received the PSWC Research Achievement Award (Pharmaceutical Sciences World Congress) in 2010 in New Orleans, from the FIP (International Pharmaceutical Federation) and the Prize of Notoriety from the French National Academy of Pharmacy in 2011. He is currently President of the departmental committee of “La Ligue contre le Cancer”.
SUMMARY OF PRESENT WORK : His interest is directed towards therapeutic nanoparticle-based strategies that do not rely on the “Enhanced Permeability and Retention” effect. Among them, the design of various implants including intracerebral systems is currently achieved. In parallel, the targeting of a particular subset of immune cells, the monocytic myeloid-derived suppressor cells (M-MDSC), localized in the lymph nodes, is studied in order to propose new avenues in nano-immunotherapy. Two European projects from the EuroNanoMed program and coordinated by Prof. Benoit (NICHE and RESOLVE) are focusing on these aspects.
MAJOR PUBLICATIONS :
ROGER E., GIMEL J. - C., BENSLEY C., KLYMCHENKO A. S., BENOÎT J. - P. « Lipid nanocapsules maintain full integrity after crossing a human intestinal epithelium model ». J Contr Rel. 2017. Vol. 253 p. 11-18
SASSO M. STELLA, LOLLO G., PITORRE M., SOLITO S., PINTON L., VALPIONE S., BASTIAT G., MANDRUZZATO S., BRONTE V., MARIGO I., BENOÎT J. - P. « Low dose gemcitabine-loaded lipid nanocapsules target monocytic myeloid-derived suppressor cells and potentiate cancer immunotherapy ». Biomaterials. 2016. Vol. 96 p. 47-62
SIMONSSON C., BASTIAT G., PITORRE M., KLYMCHENKO A. S., BEJAUD J., MÉLY Y., BENOÎT J. - P. « Inter-nanocarrier and nanocarrier-to-cell transfer assays demonstrate the risk of an immediate unloading of dye from labeled lipid nanocapsules ». Eur J Pharm Biopharm. 2016. Vol. 98 p. 47-56
WAUTHOZ N., BASTIAT G., MOYSAN E., CIEŚLAK A., KONDO K., ZANDECKI M., MOAL V., ROUSSELET M. - C., HUREAUX J., BENOÎT J. - P. « Safe lipid nanocapsule-based gel technology to target lymph nodes and combat mediastinal metastases from an orthotopic non-small-cell lung cancer model in SCID-CB17 mice ». Nanomedicine: Nanotechnology, Biology and Medicine. 2015. Vol. 11 n°5 p. 1237-1245
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Abstract |
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Nanoparticle-based therapeutics in Oncology |
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Nanomedicine, an emerging new field created by the fusion of nanotechnology and medicine, is one of the most promising pathways for the development of effective targeted therapies with oncology being the earlier and the most notable beneficiary to date. Indeed, drug-loaded nanosystems provide an ideal solution to overcome the low selectivity of the anticancer drugs towards the cancer cells in regards to normal cells and the induced severe side effects, thanks to their passive and/or active targeting to cancer tissues. Nanoparticle and liposome-based systems encapsulating drugs are already used in some cancer therapies. They can be classified according to their stability in the blood stream. For stable systems, the first generation of nanocarriers targets the reticulo-endothelial system (RES) due to opsonization that occurs on the nanocarrier surface. Even though this way of targeting is simple, a number of nanomedicines are on the market (Myocet®/breast cancer, Daunoxome®/Kaposi’s sarcoma, Vyxeos®/acute myeloid leukemia,…). From this point, RES-avoiding nanocarriers have been developed and allow a passive targeting of the tumors based on the enhanced permeability and retention effect (EPR): they constitute the second generation with specialities on the market such as Caelyx® (ovarian cancer), Onivyde® (pancreas cancer)… in therapeutics or Sinerem® in diagnostics.
A third generation of nanocarriers is under development where a ligand is attached to the nanosystem surface to recognize a specific biomarker overexpressed by the cancer cells.
However, the mechanism of action of the two latter generations of nanocarriers relies on the EPR effect. Unfortunately, many aggressive tumors are poorly vascularized what represents a severe limitation for these nanomedicines. Some advances have been made with unstable nanoparticles in the blood stream such as albumin-based nanocarriers (Abraxane®). An original mechanism of action makes them useful as an adjuvant therapy for tumors such as the pancreatic adenocarcinoma for instance.
Another strategy that allows to bypass the EPR effect in poorly vascularized cancers is the local administration of nanocarriers, directly in the tumor. In such cases, this is a physical change that is sought after (hyperthermia, ionizing radiations,…).
Nevertheless improvements are needed in drug targeting using nanoparticle-based strategies, such as more stable formulations that do not leak, more versatile systems able to encapsulate any type of drugs, control of active and sub-cellular targeting,…
In a near future, nanosystems capable to diagnose and to treat at the same time a tumor will appear on the market, opening an era of theranostics
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