Jake Brenner
@jakebrenner
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Critical Care physician, Bioengineer, Medical Entrepreneur. #nanomedicine. @PennMedicine, @PennHealthTech, @SUBiodesign alum.
Philadelphia, PA
Joined April 2009
RT @princetonideas: Can resilience be learned? A new study from @Princeton researchers finds that prior stressful events can help build res….
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RT @FrontPharmacol: New Research: Nanoparticle-Induced Augmentation of Neutrophils’ Phagocytosis of Bacteria #pharm….
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Nanomedicine Kung-Fu! 🥷 Our Advanced Materials (@AdvSciNews) paper from yesterday is featured in @PennMedNews, showing conjugated Factor I can act like a Kung-Fu Master to protect #nanoparticles & gene therapy from complement. #nanomedicine #GeneTherapy .
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Wow, we in #nanomedicine have so much to learn from nature, and our colleagues studying exosomes / extracellular vesicles. Great leadership by @H_Ghandehari & @ADDReditors to put work like this in ADDR.
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RT @MJMitchell_Lab: Check out our latest on the cover of today’s issue of @NanoLetters led by @MagBillingsley in collaboration w @carlhjune….
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Anti-vaxxers: This does NOT indicate danger of #COVID19 #vaccines. Vaccines go into your shoulder muscle, where there is no pre-existing inflammation. Our paper focuses on a risk for FUTURE applications of LNPs to express proteins to fix ARDS, sepsis, etc. #VaccinesSaveLives.
Psyched about paper with close friend & colleague Hamideh Parhiz and @WeissmanLab: Lipid #nanoparticles (LNPs) saved the world as #COVID19 vaccines & hold great promise. But when host has pre-existing inflammation at site of delivery, LNPs worsen it 10x! .
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Psyched about paper with close friend & colleague Hamideh Parhiz and @WeissmanLab: Lipid #nanoparticles (LNPs) saved the world as #COVID19 vaccines & hold great promise. But when host has pre-existing inflammation at site of delivery, LNPs worsen it 10x! .
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Excited the full version of our Advanced Materials paper just published! Factor I conjugation to #nanoparticles blocks complement activation, prolonging NP half-life, improving organ- & cell-targeting, & preventing CARPA. & super EASY!.
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Our paper in Advanced Materials (@AdvSciNews.), using Factor I to stop complement's deleterious effects on #nanomedicine, was a true team effort, & built on great work by Simberg, Moghimi, Szebeni, etc! Happy to help others use it for their nanomedicines!.
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CARPA is an #anaphylaxis-like reaction caused when complement reacts with nanoparticles (or therapeutic proteins). In sepsis model mice, #nanoparticle CARPA caused massive shock & cerebral hypoperfusion, but conjugated Factor I totally prevented this.
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Factor I conjugation also stops ligand-targeted #nanoparticles from being taken up by local phagocytes in the target organ. 🕵️Nano-spies 🕵️
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Next we injected IgG-liposmes +/- conjugated-Factor I into #sepsis model mice. Factor I prevented uptake in lung neutrophils & ⬆️ blood AUC. Complement & its ally RES tried to trap #nanomedicine, but Factor I blew thru the blockade⚓️. But the silly metaphor died in battle🧟♂️
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First we showed complement C3 massively opsonizes top-selling #nanoparticle Abraxane & PEGylated liposomes. Complement Army 🪖scored key victories. But we conjugated Factor I to PEGylated NPs, markedly decreasing C3 opsonization. Factor I guardians 🥷destroyed the invading army!
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Our new paper in Advanced Materials (@AdvSciNews) conjugates Factor I to #nanoparticles to stop complement from attacking. Even +PEG, complement opsonizes #nanoparticles ➡️ phagocyte+RES uptake, ⬇️1/2life, +CARPA. Factor I destroys complement! 🧵below
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Cute! Our lab makes #nanomedicine onesies for all our colleague-babies born into the #nanomedicine family! We've made for @KaraSpillerLab, @WeissmanLab, & we're branching into puppies (sorry, kittens). Get one for a colleague (I mean their baby, we don't condone adult onesies 🤪)
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Cool use of RBC-hitchhiking (RH) to treat #ARDS (lung inflammation that kills in #COVID19), which is my favorite disease (yes, all docs have fav diseases to battle 🥷🔫⚔️). Smart to use positively charged #nanoparticles to help adsorb onto RBCs. Just watch out for complement.
RBC-hitchhiking chitosan nanoparticles loading methylprednisolone for lung-targeting delivery. | Chunsheng Gao, Shenyang Pharmaceutical Univ. |.#chitosannanoparticle #lungdelivery .
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Ton of fun moderating a session w V Muzykantov, @WillemNANO, Jamie Spangler at IMES, hosted by @KaraSpillerLab. #nanomedicine hit only base-hits & strikeouts for 40 yrs, but hit a grand slam by partnering w immunology. Lessons from this & the other success, mRNA-LNPs?
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Who needs TikTok dance videos, when Science Twitter has far better moves? @bellapoarch is creative, but can she wiggle & penetrate cell membranes like DJ CPP? Amazingly cool work, & very instructive for the worlds of #nanomedicine, #nanotechnology, & targeted drug delivery.
It makes all the sense in the world that CPPs induce pore formation to get into cells. Cool to see convincing data after years of back-and-forth. Interesting how it is channel mediated but they don't physically pass through a channel (that was my bet).
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Great review paper! Figs 1-3 are collectively the most cogent explanation of ionizable lipid structure & function I have seen.
Chemistry of Lipid Nanoparticles for RNA Delivery | Accounts of Chemical Research
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