Peptides have important biological functions. However, their susceptibility to proteolysis limits their applications. We demonstrated here for the first time, that poly(2‐oxazoline) (POX) can work as a functional mimic of peptides. POX‐based glycine pseudopeptides, a host defense peptide mimic, had potent activities against methicillin‐resistant S. aureus, which causes formidable infections. The POX mimic showed potent activity against persisters that are highly resistant to antibiotics. S. aureus did not develop resistance to POX owning to the reactive oxygen species related antimicrobial mechanism. POX‐treated S. aureus is sensitive to common antibiotics, demonstrating no observable antimicrobial pressure or cross‐resistance in using antimicrobial POX. This study highlights POX as a new type of functional mimic of peptides and opens new avenues in designing and exploring peptide mimetics for biological functions and applications.
Varying cytotoxicity of HAPNs was observed in different cancer cell types. Our results suggest that possible mechanisms of cytotoxicity in various types of cancer cells could be different. The elevated calcium concentration and nuclear localization of the particles might be the main mechanism of growth inhibition by HAPNs in cancer cells.
Peptides have important biological functions. However, their susceptibility to proteolysis limits their applications. We demonstrated here for the first time, that poly(2‐oxazoline) (POX) can work as a functional mimic of peptides. POX‐based glycine pseudopeptides, a host defense peptide mimic, had potent activities against methicillin‐resistant S. aureus, which causes formidable infections. The POX mimic showed potent activity against persisters that are highly resistant to antibiotics. S. aureus did not develop resistance to POX owning to the reactive oxygen species related antimicrobial mechanism. POX‐treated S. aureus is sensitive to common antibiotics, demonstrating no observable antimicrobial pressure or cross‐resistance in using antimicrobial POX. This study highlights POX as a new type of functional mimic of peptides and opens new avenues in designing and exploring peptide mimetics for biological functions and applications.
Light-cross-linked
small-molecule micelles with enediyne units are designed for developing
efficient drug-delivery systems. Gemcitabine (GEM) is chosen as a
model hydrophilic drug and tethered with a maleimide-based enediyne
(EDY) as a hydrophobic tail in the preparation of amphiphilic EDY–GEM.
The stable micellar particles are obtained by cross-linking the enediyne
moieties via photoinduced Bergman cyclization polymerization in aqueous
media. The light-cross-linked spherical micelles with a size of 80
nm are characterized with dynamic light scattering and electron microscopy,
showing robust micellar stability, bright fluorescent emission due
to their intrinsic conjugated structure, and potential passive tumor-targeting
ability through the enhanced permeability and retention effect. The
drug-loaded micelles, as an example of light-cross-linked small-molecule
micelle-based drug-delivery system, exhibit high drug-loading contents
(50%) and greatly improved cytotoxicity toward A549 cells (decreasing
the IC50 value of Gemcitabine by 10 times), thanks to the
greatly increased cellular uptake of the drug-loaded micelles as confirmed
by confocal laser scanning microscopy. The light-cross-linked enediyne-based
small-molecule micelles system therefore provides a simple yet efficient
drug-delivery platform for cancer chemotherapy.
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