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Screening for bilayer-active and likely cytotoxic molecules reveals bilayer-mediated regulation of cell function.
J Gen Physiol
April 2023
Department of Physiology and Biophysics, Weill Cornell Medicine , New York, NY, USA.
A perennial problem encountered when using small molecules (drugs) to manipulate cell or protein function is to assess whether observed changes in function result from specific interactions with a desired target or from less specific off-target mechanisms. This is important in laboratory research as well as in drug development, where the goal is to identify molecules that are unlikely to be successful therapeutics early in the process, thereby avoiding costly mistakes. We pursued this challenge from the perspective that many bioactive molecules (drugs) are amphiphiles that alter lipid bilayer elastic properties, which may cause indiscriminate changes in membrane protein (and cell) function and, in turn, cytotoxicity.
View Article and Find Full Text PDFCombating Escherichia coli O157:H7 with Functionalized Chickpea-Derived Antimicrobial Peptides.
Adv Sci (Weinh)
February 2023
College of Biosystems Engineering and Food Science, National-Local Joint Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang University, Hangzhou, Zhejiang Province, 310058, P. R. China.
The rapid dissemination of antibiotic resistance accelerates the desire for new antibacterial agents. Here, a class of antimicrobial peptides (AMPs) is designed by modifying the structural parameters of a natural chickpea-derived AMP-Leg2, termed "functionalized chickpea-derived Leg2 antimicrobial peptides" (FCLAPs). Among the FCLAPs, KTA and KTR show superior antibacterial efficacy against the foodborne pathogen Escherichia coli (E.
View Article and Find Full Text PDFEngineered biomimetic nanoreactor for synergistic photodynamic-chemotherapy against hypoxic tumor.
J Control Release
November 2022
Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address:
Photodynamic therapy (PDT) can produce a large amount of reactive oxygen species (ROS) in the radiation field to kill tumor cells. However, the sustainable anti-tumor efficacy of PDT is limited due to the hypoxic microenvironment of tumor. In this study, classic PDT agent indocyanine green (ICG) and hypoxia-activated chemotherapeutic drug tirapazamine (TPZ) were loaded on mesoporous polydopamine (PDA) to construct PDA@ICG-TPZ nanoparticles (PIT).
View Article and Find Full Text PDFTMEM164 is a new determinant of autophagy-dependent ferroptosis.
Autophagy
March 2023
Center for DAMP Biology, Department of Surgery, UT Southwestern Medical Center, Dallas, TX, USA.
Macroautophagy (hereafter "autophagy") is a membrane-mediated biological process that involves engulfing and delivering cytoplasmic components to lysosomes for degradation. In addition to autophagy's pro-survival effect during nutrient starvation, excessive activation of autophagy machinery can also cause regulated cell death, especially iron-dependent ferroptosis. Here, we report a key role of TMEM164 (transmembrane protein 164) in selectively mediating ATG5 (autophagy related 5)-dependent autophagosome formation during ferroptosis, rather than during starvation.
View Article and Find Full Text PDFTumor-associated macrophage membrane-camouflaged pH-responsive polymeric micelles for combined cancer chemotherapy-sensitized immunotherapy.
Int J Pharm
August 2022
Department of Cell Biology and Medical Genetics, School of Medicine, Yanbian University, 977 Gongyuan Road, Yanji, Jilin 133002, China. Electronic address:
The low immunogenicity and tumor immunosuppressive microenvironment (TIM) are two major obstacles for cancer immunotherapy. Synergistically immunogenic cell death induction and tumor-associated macrophages depletion could perfectly overcome this limitation. Herein, a tumor-associated macrophage (TAMs) membrane-camouflaged pH-responsive doxorubicin (DOX) loaded hyaluronic acid (HA)-g-poly (histidine) polymeric micelles (DHP@M2) was fabricated for the first time.
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