Injectable
and sprayable hydrogels have attracted considerable attention for
application in the biomedical field owing to their high moldability
and efficiency in encapsulating therapeutics and cells. Herein, we
report the spontaneous assembly of injectable and sprayable hydrogels
via a one-step mixing of solutions of tannic acid (TA) and O-carboxymethyl chitosan (CMCS) without an external stimulus.
The presence of 1,4-benzenediboronic acid (BDBA) improves the mechanical
properties and reduces the gelation time of the resulting hydrogels.
The hydrogels assemble via hydrogen bonds between TA and CMCS as well
as via dynamic boronate ester bonds between TA and BDBA, as confirmed
by Fourier transform infrared spectroscopy. Balancing the interactions
between the three components (CMCS/TA/BDBA) is essential for the construction
of the hydrogels. The moduli of the CMCS–TA–BDBA hydrogels
initially increase as the amount of BDBA increases and decrease after
reaching a maximum value at a BDBA-to-TA molar ratio of 3:1. The CMCS–TA–BDBA
hydrogels with interconnected porous morphologies display rapid gelation
(∼10 s), biocompatibility, self-healing, injectable, and sprayable
abilities. In addition, the hydrogels can be used for hemostasis.
The extent of bleeding in mouse livers treated with the hydrogels
could be reduced extensively from 240 (nontreated mouse livers) to
55 mg (77% reduction). The reported hydrogels coupled with the combination
of functionality and biological activity make them promising hemostatic
materials for biomedical applications.
Cancer stem cell theory indicates cancer stem cells are the key to promote tumor invasion and metastasis. Studies showed that BMI-1 could promote self-renew, differentiation and tumor formation of CSCs and invasion/metastasis of human cancer. However, whether BMI-1 could regulate invasion and metastasis ability of CSCs is still unclear. In our study, we found that up-regulated expression of BMI-1 was associated with tumor invasion, metastasis and poor survival of pancreatic cancer patients. CD133+ cells were obtained by using magnetic cell sorting and identified of CSCs properties such as self-renew, multi-differentiation and tumor formation ability. Then, we found that BMI-1 expression was up-regulated in pancreatic cancer stem cells. Knockdown of BMI-1 expression attenuated invasion ability of pancreatic cancer stem cells in Transwell system and liver metastasis capacity in nude mice which were injected CSCs through the caudal vein. We are the first to reveal that BMI-1 could promote invasion and metastasis ability of pancreatic cancer stem cells. Finally, we identified that BMI-1 expression activating PI3K/AKT singing pathway by negative regulating PTEN was the main mechanism of promoting invasion and metastasis ability of pancreatic CSCs. In summary, our findings indicate that BMI-1 could be used as the therapeutic target to inhibiting CSCs-mediated pancreatic cancer metastasis.
We report the one-step assembly of
vaccine particles by encapsulating
ovalbumin (OVA) and cytosine-phosphate-guanine oligodeoxynucleotides
(CpG) into poly(ethylene glycol) (PEG)-mediated zeolitic imidazolate
framework-8 nanoparticles (OVA-CpG@ZIF-8 NPs), where PEG improves
the stability and dispersity of ZIF-8 NPs and the NPs protect the
encapsulated OVA and CpG to circumvent the cold chain issue. Compared
with free OVA and OVA-encapsulated ZIF-8 (OVA@ZIF-8) NPs, OVA-CpG@ZIF-8
NPs can enhance antigen uptake, cross-presentation, dendritic cell
(DC) maturation, production of specific antibody and cytokines, and
CD4+ T and CD8+ T cell activation. More importantly,
the vaccine particles retain their bioactivity against enzymatic degradation,
elevated temperatures, and long-term storage at ambient temperature.
The study highlights the importance of PEG-mediated ZIF-8 NPs as a
vaccine delivery system for the promising application of effective
and cold chain-independent vaccination against diseases.
Mineralization of metal-organic frameworks (MOFs) has shown potential in the encapsulation of functional biomacromolecules and therapeutics. One of the challenges is to improve the stability of MOFs in aqueous solution....
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