RAFT Emulsion Polymerization as a Platform to Generate Well‐Defined Biocompatible Latex Nanoparticles
The first paper in collaboration with the group of Prof. Seb Perrier (Warwick Chemistry)
Current approaches to generate core–shell nanoparticles for biomedical applications are limited by factors such as synthetic scalability and circula- tory desorption of cytotoxic surfactants. Developments in controlled radical polymerization, particularly in dispersed states, represent a promising method of overcoming these challenges. In this work, well-defined PEGylated nanoparticles are synthesized using reversible addition fragmentation chain transfer emulsion polymerization to control particle size and surface compo- sition and were further characterized with light scattering, electron micros- copy, and size exclusion chromatography. Importantly, the nanoparticles are found to be tolerated both in vitro and in vivo, without the need for any puri- fication after particle synthesis. Pharmacokinetic and biodistribution studies in mice, following intraperitoneal injection of the nanoparticles, reveal a long (>76 h) circulation time and accumulation in the liver.
Circadian rest-activity rhythm as an objective biomarker of patient-reported outcomes in patients with advanced cancer
Collaboration lead by Pasquale Innominato
In this international observational study including two independent cohorts of patients with advanced cancers, an objective measure of circadian function was significantly associated with symptoms’ score severity and health-related quality of life. Circadian rest-activity pattern monitoring through wearable devices provides a reliable, consistent and continuous biomarker that identifies several psychosocial dimensions.
Mitochondrial fission-fusion dynamics and mitochondrial bioenergetics, including oxidative phosphorylation and generation of ATP, are strongly clock controlled. Here we show that these circadian oscillations depend on circadian modification of dynamin-related protein 1 (DRP1), a key mediator of mitochondrial fission. We used a combination of in vitro and in vivo models, including human skin fibroblasts and DRP1-deficient or clock-deficient mice, to show that these dynamics are clock controlled via circadian regulation of DRP1. Genetic or pharmacological abrogation of DRP1 activity abolished circadian network dynamics and mitochondrial respiratory activity and eliminated circadian ATP production. Pharmacological silencing of pathways regulating circadian metabolism and mitochondrial function (e.g., sirtuins, AMPK) also altered DRP1 phosphorylation, and abrogation of DRP1 activity impaired circadian function. Our findings provide new insight into the crosstalk between the mitochondrial network and circadian cycles.
First collaboration manuscript between Warwick and Paris
Everolimus (EV), a rapamycin analogue mTOR inhibitor, is used in the clinic to treat Estrogen positive (ER+) breast cancer in order to avoid the resistance to hormonotherapy. Here, we investigate if EV has different effects dependent on time of administration.
|A new publication on a slightly more zoological topic: “The Bear Circadian Clock Doesn’t “Sleep” in Hibernation” in Frontiers of Zoology. The paper from lead author Heiko Jansen extends out knowledge on the responsiveness of the circadian clock during “hibernation” in bears. Even in torpid animals housed in constant conditions the clock remains responsive to stimuli light light. It also shows that bear fibroblasts grow really well in culture and human Bmal1 reporter constructs are useful to study their cellular clocks.|