Peptide nanozymes:An emerging direction for functional enzyme mimics

The abundance of molecules on early Earth likely enabled a wide range of prebiotic chemistry,with peptides playing a key role in the development of early life forms and the evolution of metabolic pathways.Among peptides,those with enzyme-like activities occupy a unique position between peptides and enzymes,combining both structural flexibility and catalytic functionality.However,their full potential remains largely untapped.Further exploration of these enzyme-like peptides at the nanoscale could provide valuable insights into modern nanotechnology,biomedicine,and even the origins of life.Hence,this review introduces the groundbreaking concept of“peptide nanozymes(PepNzymes)”,which includes single peptides exhibiting enzyme-like activities,peptide-based nanostructures with enzyme-like activities,and peptide-based nanozymes,thus enabling the investigation of biological phenomena at nanoscale dimensions.Through the rational design of enzyme-like peptides or their assembly with nanostructures and nanozymes,researchers have found or created PepNzymes capable of catalyzing a wide range of reactions.By scrutinizing the interactions between the structures and enzyme-like activities of PepNzymes,we have gained valuable insights into the underlying mechanisms governing enzyme-like activities.Generally,PepNzymes play a crucial role in biological processes by facilitating small-scale enzyme-like reactions,speeding up molecular oxidation-reduction,cleavage,and synthesis reactions,leveraging the functional properties of peptides,and creating a stable microenvironment,among other functions.These discoveries make PepNzymes useful for diagnostics,cellular imaging,antimicrobial therapy,tissue engineering,anti-tumor treatments,and more while pointing out opportunities.Overall,this research provides a significant journey of PepNzymes’potential in various biomedical applications,pushing them towards new advancements.

Nanobody-based chimeric antigen receptor T cells designed by CRISPR/Cas9 technology for solid tumor immunotherapy

Chimeric antigen receptor-based T-cell immunotherapy is a promising strategy for treatment of hematological malignant tumors;however,its efficacy towards solid cancer remains challenging.We therefore focused on developing nanobody-based CAR-T cells that treat the solid tumor.CD105 expression is upregulated on neoangiogenic endothelial and cancer cells.CD105 has been developed as a drug target.Here we show the generation of a CD105-specific nanobody,an anti-human CD105 CAR-T cells,by inserting the sequences for anti-CD105 nanobody-linked standard cassette genes into AAVS1 site using CRISPR/Cas9 technology.Co-culture with CD105+target cells led to the activation of anti-CD105 CAR-T cells that displayed the typically activated cytotoxic T-cell characters,ability to proliferate,the production of pro-inflammatory cytokines,and the specific killing efficacy against CD105+target cells in vitro.The in vivo treatment with anti-CD105 CAR-T cells significantly inhibited the growth of implanted CD105+tumors,reduced tumor weight,and prolonged the survival time of tumor-bearing NOD/SCID mice.Nanobody-based CAR-T cells can therefore function as an antitumor agent in human tumor xenograft models.Our findings determined that the strategy of nanobody-based CAR-T cells engineered by CRISPR/Cas9 system has a certain potential to treat solid tumor through targeting CD105 antigen.