ACS Appl Mater Interfaces
January 2025
Common treatment approaches for triple-negative breast cancer (TNBC) are associated with severe side effects due to the unfavorable biodistribution profile of potent chemotherapeutics. Here, we explored the potential of TNBC-targeting aptamer-decorated porous silicon nanoparticles (pSiNPs) as targeted nanocarriers for TNBC. A "salt-aging" strategy was employed to fabricate a TNBC-targeting aptamer functionalized pSiNP that was highly colloidally stable.
View Article and Find Full Text PDFSignal-dependent transport into and out of the nucleus mediated by members of the importin (IMP) superfamily is crucial for eukaryotic function, with inhibitors targeting IMPα being of key interest as anti-infectious agents, including against the apicomplexan species and , causative agents of malaria and toxoplasmosis, respectively. We recently showed that the FDA-approved macrocyclic lactone ivermectin, as well as several other different small molecule inhibitors, can specifically bind to and inhibit and IMPα functions, as well as limit parasite growth. Here we focus on the FDA-approved antiparasitic moxidectin, a structural analogue of ivermectin, for its IMPα-targeting and anti-apicomplexan properties for the first time.
View Article and Find Full Text PDFBackground: Nuclear import, dependent on the transporter importin α (IMPα), is a drug target for apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii. Indeed, a panel of small molecule inhibit interactions between IMPα and nuclear localization signals (NLSs) in vitro and the growth of rapidly dividing stages (P. falciparum blood stages and T.
View Article and Find Full Text PDFApolipoprotein E (ApoE) polymorphisms modify the risk of Alzheimer's disease with ApoE4 strongly increasing and ApoE2 modestly decreasing risk relative to the control ApoE3. To investigate how ApoE isoforms alter risk, we measured changes in proteome homeostasis in transgenic mice expressing a human ApoE gene (isoform 2, 3, or 4). The regulation of each protein's homeostasis is observed by measuring turnover rate and abundance for that protein.
View Article and Find Full Text PDFApolipoprotein E (ApoE) polymorphisms modify the risk of neurodegenerative disease with the ApoE4 isoform increasing and ApoE2 isoform decreasing risk relative to the 'wild-type control' ApoE3 isoform. To elucidate how ApoE isoforms alter the proteome, we measured relative protein abundance and turnover in transgenic mice expressing a human ApoE gene (isoform 2, 3, or 4). This data provides insight into how ApoE isoforms affect the synthesis and degradation of a wide variety of proteins.
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