The
design of bioactive supramolecular chirality is always hampered
by the lack of feasible schemes to assigned specific biological activities.
Herein, we developed a “mirror-image peptide grafting”
method to graft the epitopes of bioactive d-peptide onto
the miniprotein template to construct a self-assembled supraparticle.
Grafting DPMIβ, a 12-mer d-enantiomeric
peptide functioned as the p53 agonist, onto Apamin, we successfully
constructed a self-assembled d-enantiomeric miniprotein supermolecule
nanoparticle, termed DMSN. This chiral supraparticle possesses
a favorable pharmaceutical profile including the passive tumor targeting,
cell membrane penetration, intracellular reductive responsiveness,
and endosome escaping. DMSN showed in vitro and in vivo p53-dependent antiproliferative activity
and augmented antitumor immunity elicited by anti-PD1 therapy. This
enabling strategy will allow us to fabricate a class of peptide/protein-derived
supramolecular chirality with predictable biological activities and
will likely have a broad impact on the chiral nanotechnology at the
service of prevention and treatment of human diseases.
Slow light has been widely utilized to obtain enhanced nonlinearities, enhanced spontaneous emissions and increased phase shifts owing to its ability to promote light–matter interactions. By incorporating a graphene on a slow-light silicon photonic crystal waveguide, here we experimentally demonstrate an energy-efficient graphene microheater with a tuning efficiency of 1.07 nmmW−1 and power consumption per free spectral range of 3.99 mW. The rise and decay times (10–90%) are only 750 and 525 ns, which, to the best of our knowledge, are the fastest reported response times for microheaters in silicon photonics. The corresponding figure of merit of the device is 2.543 nW s, one order of magnitude better than results reported in previous studies. The influence of the length and shape of the graphene heater to the tuning efficiency is further investigated, providing valuable guidelines for enhancing the tuning efficiency of the graphene microheater.
Developing a sophisticated nanomedicine platform to deliver therapeutics effectively and safely into tumor/cancer cells remains challenging in the field of nanomedicine. In particular, reliable peptide drug delivery systems capable of overcoming biological barriers are still lacking. Here, we developed a simple, rapid, and robust strategy to manufacture nanoclusters of ∼90 nm in diameter that are self-assembled from lanthanide-doped nanoparticles (5 nm), two anticancer peptides with different targets (BIM and PMI), and one cyclic peptide iNGR targeted to cancer cells. The peptide-lanthanide nanoclusters (LDC-PMI-BIM-iNGR) enhanced the resistance of peptide drugs to proteolysis, disassembled in response to reductive conditions that are present in the tumor microenvironment and inhibited cancer cell growth in vitro and in vivo. Notably, LDC-PMI-BIM-iNGR exhibited extremely low systemic toxicity and side effects in vivo. Thus, the peptide-lanthanide nanocluster may serve as an ideal multifunctional platform for safe, targeted, and efficient peptide drug delivery in cancer therapy.
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