In
this work, we prepared a novel cancer chemotherapeutic nanocarrier
through the self-assembly of a mussel-derived, cancer-targeting peptide
with a pH-sensitive conjugation of antitumor drugs. The biomimetic
peptide was designed with a fluorescent molecule fluorescein isothiocyanate
for imaging, a RGD sequence for cancer-targeting and tetravalent catechol
groups for dynamic conjugation of the antitumor drug bortezomib via
pH-cleavable boronic acid–catechol esters. Our study demonstrated
that the peptide-based prodrug nanocarrier dramatically the enhanced
specific cellular uptake and cytotoxicity toward human breast cancer
cells in vitro in comparison with free drug and nontargeting control
nanoparticles. Likewise, the prodrug nanocarrier showed improved therapeutic
efficacy and low systematic toxicity in vivo. Considering highly biomimetic
nature of the peptide-based nanocarriers, rapid drug release from
the dynamically conjugated prodrugs, and convenience of introducing
cancer-targeting activity onto this nanosystem, we believe our work
would provide new ideas for the development of intelligent and biocompatible
drug delivery systems to improve the chemotherapy efficacy in clinic.
Furthermore, the pH-sensitive drug conjugation mechanism on peptide-based
nanocarriers would provide a hint for the exploitation of dynamic
prodrug strategies and the development of highly biocompatible nanocarriers
using biogenic materials, e.g., the proteinogenic nanomaterials decorated
with drugs through dynamic covalent chemistry.
Simulation of self-recovery and diversity of natural photonic crystal (PC) structures remain great challenges for artificial PC materials. Motivated by the dynamic characteristics of PC nanostructures, here, we present a new strategy for the design of hydrogel-based artificial PC materials with reversible interactions in the periodic nanostructures. The dynamic PC hydrogels, derived from self-assembled microgel colloidal crystals, were tactfully constructed by reversible crosslinking of adjacent microgels in the ordered structure via phenylboronate covalent chemistry. As proof of concept, three types of dynamic colloidal PC hydrogels with different structural colors were prepared. All the hydrogels showed perfect self-healing ability against physical damage. Moreover, dynamic crosslinking within the microgel crystals enabled shear-thinning injection of the PC hydrogels through a syringe (indicating injectability or printability), followed by rapid recovery of the structural colors. In short, in addition to the great significance in biomimicry of self-healing function of natural PC materials, our work provides a facile strategy for the construction of diversified artificial PC materials for different applications such as chem-/biosensing, counterfeit prevention, optical display, and energy conversion.
We utilized one-step multiplex reverse transcription-PCR (RT-PCR) and Luminex xMAP technology to develop a respiratory multiplex liquid-chip assay (rMLA) for simultaneous detection of 6 common respiratory viruses, including influenza virus type A (FluA) and type B (FluB), para-influenza virus type 3 (PIV-3), respiratory syncytial virus (RSV), human metapneumovirus (MPV) and a threatening virus to China, Middle East Respiratory Syndrome coronavirus (MERS-CoV). Performance of rMLA was evaluated by comparing with real-time RT-PCR. Detection data from clinical specimens showed that the rMLA had diagnostic sensitivities of 97.10% for FluA, 94.59% for FluB, 98.68% for PIV-3, 94.87% for RSV and 95.92% for MPV (No Data for MERS-CoV due to the lack of positive specimens). Data of analytical sensitivities showed that the detection limits of the rMLA assay were 5–25 viral RNA copies per μl for FluA, FluB, PIV-3 and MERS-CoV, approximate to the real-time RT-PCR assay; while the values were 8 and 22copies/μl for MPV and RSV, lower than the real-time RT-PCR(78 and 114 copies/μl respectively). The results indicated that the rMLA is a sensitive, specific detection tool and comparable to real-time RT-PCR, especially suitable for high-throughput detection of respiratory specimens.
pR(ST98), a chimeric plasmid isolated from Salmonella enterica serovar typhi (S. typhi), is involved in bacterial multidrug-resistance and virulence, however, its exact contributions to bacterial pathogenesis are still not fully understood. To investigate whether pR(ST98) exhibits potential to mediate macrophage autophagy and apoptosis, murine macrophage-like cell line (J774A.1) was infected with wild type strain (S. typhi-WT), mutant strain (S. typhi-DeltapR(ST98)) and complement of S. typhi-DeltapR(ST98) (S. typhi-c-pR(ST98)). Results revealed that S. typhi harboring pR(ST98) decreased the number of autophagy vacuoles of macrophages as well as the expression of Beclin 1 and LC3-II at the early stage of infection; apoptosis rate of macrophages infected with S. typhi-DeltapR(ST98) was lower than that infected with S. typhi-WT or S. typhi-c-pR(ST98). The survival rate of intracellular bacteria carrying pR(ST98) was much higher than that of plasmid free strain. After intervention with autophagy agonist rapamycin, apoptosis rate of the cells infected with S. typhi containing pR(ST98) and intracellular bacterial growth decreased. Our study suggested that pR(ST98) could inhibit autophagy and induce cell apoptosis for the host bacterial survival and proliferation.
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