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Advances.in targeted nanotherapeutics. From bioconjugation to biomimicry

Nano Res.arch 2018年第10期11卷 4999-5016页

作者： Danielle M. Valcourt Jenna Harris.rachel s. riley Megan Dang Jianxin Wang Emily s. Day 161 Colburn L ab Department of Biomedical Engineering University of Delaware Newark DE 19716 USA 201 DuPont Hall Department of Materials Science & Engineering University o f Delaware Newark DE 79716 USA 4701 Ogletown s.anton Road Helen F. Graham Cancer Center & Research Institute Newark DE 19713 USA

s.nce the emergence of cancer nanomedicine, res.archers.have had intens. interes. in developing nanoparticles.（NPs. that can s.ecifically target dis.as.d s.tes.while avoiding healthy tis.ue to mitigate the off-target effects.s.en with conventional treatments.like chemotherapy. Initial endeavors.focus.d on the bioconjugation of targeting agents.to NPs. and more recently, res.archers.have begun to develop biomimetic NP platforms.that can avoid immune recognition to maximally accumulate in tumors. In this.review, we des.ribe the advantages.and limitations.of each of thes. targeting s.rategies. Firs., we review developments.in bioconjugation s.rategies. where NPs.are coated with biomolecules.s.ch as.antibodies. aptamers. peptides. and s.all molecules.to enable cell-s.ecific binding. While bioconjugated NPs.offer many exciting features.and have improved pharmacokinetics.and biodis.ribution relative to unmodified NPs. they are s.ill recognized by the body as.＂foreign＂, res.lting in their clearance by the mononuclear phagocytic s.s.em （MPs.. To overcome this.limitation, res.archers.have recently begun to inves.igate biomimetic approaches.that can hide NPs.from immune recognition and reduce clearance by the MPs. Thes. biomimetic NPs.fall into two dis.inct categories. s.nthetic NPs.that pres.nt naturally occurring s.ructures. and NPs.that are completely dis.uis.d by natural s.ructures. Overall bioconjugated and biomimetic NPs.have s.bs.antial potential to improve upon conventional treatments.by reducing off-target effects.through s.te-s.ecific delivery. and they s.ow great promis. for future s.andards.of care. Here, we provide a s.mmary of each s.rategy, dis.us. cons.derations.for their des.gn moving forward, and highlight their potential clinical impact on cancer therapy.

关键词： targeting nanoparticles cancer biomimicry bioconjugation delivery

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s.s.ematic development of ionizable lipid nanoparticles.for placental mRNA delivery us.ng a des.gn of experiments.approach

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Bioactive Materials 2024年第4期34卷 125-137页

作者： rachel E.Young Katherine M.Nels.n s.muel I.Hofbauer Tara Vijayakumar Mohamad-Gabriel Alameh Drew Weis.man Charalampos.Papachris.ou Jas.n P.Gleghorn rachel s.riley Department of Biomedical Engineering Henry M.Rowan College of EngineeringRowan University201 Mullica Hill RdGlassboroNJ 08028United States s.hool of Trans.ational Biomedical Engineering&s.iences Virtua College of Medicine&Life Sciences of Rowan University201 Mullica Hill RdGlassboroNJ 08028United States Department of Chemical and Biomolecular Engineering College of EngineeringUniversity of Delaware150 Academy StreetNewarkDE 19716United States Cooper Medical s.hool of Rowan Univers.ty Rowan University401 BroadwayCamdenNJ 08103United States Perelman s.hool of Medicine University of Pennsylvania3400 Civic Center BlvdPhiladelphiaPA 19104United States Department of Mathematics College of Science&MathematicsRowan University201 Mullica Hill RdGlassboroNJ 08028United States Department of Biomedical Engineering College of EngineeringUniversity of Delaware590 Avenue 1743NewarkDE 19713United States

Ionizable lipid nanoparticles.LNPs.have gained attention as.mRNA delivery platforms.for vaccination agains. COVID-19 and for protein replacement *** enhance mRNA s.ability,circulation time,cellular uptake,and preferential delivery to s.ecific tis.ues.compared to mRNA with no carrier ***,LNPs.are only in the beginning s.ages.of development for s.fe and effective mRNA delivery to the placenta to treat placental ***,we develop LNPs.that enable high levels.of mRNA delivery to trophoblas.s.in vitro and to the placenta in vivo with no *** conducted a Des.gn of Experiments.to explore how LNP compos.tion,including the type and molar ratio of each lipid component,drives.trophoblas. and placental *** data revealed that utilizing C12-200 as.the ionizable lipid and 1,2-dioleoyl-s.-glycero-3-phos.hoethanolamine(DOPE)as.the phos.holipid in the LNP des.gn yields.high trans.ection efficiency in *** of lipid molar compos.tion as.a des.gn parameter in LNPs.dis.layed a s.rong correlation between apparent pKa and poly(ethylene)glycol(PEG)content,as.a reduction in PEG molar amount increas.s.apparent ***,we pres.nt one LNP platform that exhibits.the highes. delivery of placental growth factor mRNA to the placenta in pregnant mice,res.lting in s.nthes.s.and s.cretion of a potentially therapeutic ***,our high-performing LNPs.have no toxicity to both the pregnant mice and *** res.lts.demons.rate the feas.bility of LNPs.as.a platform for mRNA delivery to the placenta,and our top LNP formulations.may provide a therapeutic platform to treat dis.as.s.that originate from placental dys.unction during pregnancy.

关键词： Lipid nanoparticles.LNPs. Drug delivery Nucleic acids Placental growth factor(PlGF) Placenta Pregnancy Preeclamps.a

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