Special enzymes, like "Easter Eggs" with wonderful functions for biotechnology

We guess you know very well what an Easter Egg is in a video game: a special surprise that was hidden in a secret area or a bonus object. We discovered [Morra et al., 2016a, check Bibliography for info and link to this original scientific paper and to other papers cited] a similar “Easter Egg” in a protein that functions in a very useful bacterium, and this suggested us how proteins and enzymes can contribute to a bio-sustainable future. But first let us introduce you the scientific background and the context. Continua a leggere..

Enzimi speciali come "Easter Eggs" con funzioni meravigliose per le biotecnologie

Immaginiamo che sappiate bene cosa sia un "Easter Egg" in un videogioco: una sorpresa speciale nascosta in un'area segreta o un oggetto bonus. Abbiamo scoperto [Morra et al, 2016, cercalo nelle referenze, troverai il link all’articolo scientifico originale] un "Easter Egg" simile in una proteina che funziona in un batterio molto utile, e questo ci ha suggerito come proteine ed enzimi possano contribuire a un futuro bio-sostenibile. Ma prima lasciate che vi presentiamo il background scientifico e il contesto. Continua a leggere..

Enzimi speciali come "Easter Eggs" con funzioni meravigliose per le biotecnologie

Immaginiamo che sappiate bene cosa sia un "Easter Egg" in un videogioco: una sorpresa speciale nascosta in un'area segreta o un oggetto bonus. Abbiamo scoperto [Morra et al, 2016, cercalo nelle referenze, troverai il link all’articolo scientifico originale] un "Easter Egg" simile in una proteina che funziona in un batterio molto utile, e questo ci ha suggerito come proteine ed enzimi possano contribuire a un futuro bio-sostenibile. Ma prima lasciate che vi presentiamo il background scientifico e il contesto. Continua a leggere..

Nanoparticules à base du squalene pour le traitement ciblé du cancer du pancréas

Pancreatic cancer is a lethal disease with the worst prognosis among all solid tumors. In the last decades, progresses in pancreatic cancer therapy had remained exceedingly slow and disappointing offering minimal benefits in median survival which remains of less than 6 months and the maximum of 5 years in the 6% of patients. One of the major requirements for a successful cancer therapy is its ability to selectively kill cancer cells with minimal damage to healthy tissues. In this context, a great deal of attention focused on advanced nanoscale systems (i.e., nanomedicines) with the aim to overcome the limits associated to the traditional drug delivery modalities. Nanomedicines can indeed enhance drug properties by (i) offering protection from degradation, (ii) enabling controlled release and distribution and increasing bioavailability while reducing undesired side effects.In the current work we aimed to propose novel nanoscale-based strategies to optimize pancreatic cancer treatment taking into account the specific physio-pathology of this tumor. The first approach relied on the design of a targeted nanomedicine able to specifically bind receptors mainly expressed onto pancreatic cancer cells in order to selectively increase drug accumulation in these cells saving healthy ones.In a second approach, by combining two therapeutic agents in the same nanoparticle we constructed a multi-therapeutic drug delivery system capable to increase the therapeutic index of the combined therapy. In particular, taking advantages from the “squalenoylation prodrug approach”, the research activity of this Ph.D. work lead to the to design of (i) a novel peptide-functionalized squalenoyl gemcitabine nanoparticle and (ii) a tyrosine kinase inhibitor-loaded squalenoyl gemcitabine nanoparticle. Obtained nanoparticles were investigated with respect to their physico-chemical properties and in vitro antitumor activity. The efficacy of peptide-functionalized nanoparticles in impairing tumor growth was assessed in vivo on an experimental model of pancreatic cancer.Le cancer pancréatique représente la cinquième cause de décès par cancer dans les pays occidentaux. Son mauvais pronostic (survie à 5 ans inférieure à 3,5 % des cas) est dû à l’absence de facteurs de risques spécifiques interdisant une prévention efficace, et à un diagnostic tardif qui révèle un cancer agressif chez environ 90% des patients. Actuellement, le seul traitement curatif de ce cancer est la chirurgie, mais celle-ci ne peut être envisagée que dans 10 à 15 % des cas. L’adressage de molécules thérapeutiques vers l’organe, le tissu ou la cellule malade constitue aujourd’hui un défi majeur pour le traitement des maladies humaines notamment infectieuses, cancéreuses ou d’origine génétique. C’est pour ces raisons que le développement de nanotechnologies, en tant que vecteurs de médicaments, a pris un essor considérable au cours des dernières années. Dans ce contexte, le concept de squalènisation repose sur le couplage chimique entre le squalène (SQ), un lipide naturel précurseur de la synthèse du cholestérol, et des principes actifs (notamment des molécules anticancéreuses). Les bioconjugués ainsi formés sont alors capables de s’auto-assembler en solution aqueuse pour former des nanoparticules stables de diamètres compris entre 100 et 300 nm. L’exemple de référence dans ce domaine est la nanoparticule de gemcitabine-squalène (SQdFdC) qui a donné lieu à des résultats spectaculaires in vitro sur des lignées de cellules cancéreuses humaines In vivo, les nanoparticules de gemcitabine-squalène se sont avérées beaucoup plus efficaces que la gemcitabine libre sur des tumeurs solides greffées par voie sous-cutanée ainsi que sur des modèles murins de leucémies agressives métastatiques.Au vu de ces résultats encourageants, le projet de thèse a été développé autour de deux axes de recherche. (I) Dans un premier temps, les nanoparticules de gemcitabine-squalène ont été fonctionnalisées par un peptide capable de reconnaître et de cibler spécifiquement les cellules cancéreuses pancréatiques. (II) Le deuxième axe de recherche a visé l’encapsulation d’un second principe actif au sein des nanoparticules de gemcitabine-squalène afin de développer le concept de nanoparticule « multi-thérapeutique »

Bare and Effective Charge of Mesoporous Silica Particles

We develop and combine a novel numerical model, within the Poisson−Boltzmann framework, with classical experimental titration techniques for mesoporous silica particles to study the charging behavior as both pH and the amount of monovalent salt are varied. One key finding is that these particles can be considered to have an effectively or apparent electroneutral inner core with an effectively charged rim. As a consequence, the total apparent charge of the particle is several orders of magnitude smaller than that of the bare silica charge, which accounts only for the charged silanol groups of the mesoporous silica particles and which has its major contribution from the interior. Hence, the interior dictates the mesoporous silicas’ bare charge while the rim its effective charge. We furthermore report density, charge, and accumulated charge profiles across the particle’s interface