Acid-decomposable, luminescent ZnO quantum dots (QDs) have been employed to seal the nanopores of mesoporous silica nanoparticles (MSNs) in order to inhibit premature drug (doxorubicin) release. After internalization into HeLa cells, the ZnO QD lids are rapidly dissolved in the acidic intracellular compartments, and as a result, the loaded drug is released into the cytosol from the MSNs. The ZnO QDs behave as a dual-purpose entity that not only acts as a lid but also has a synergistic antitumor effect on cancer cells. We anticipate that these nanoparticles may prove to be a significant step toward the development of a pH-sensitive drug delivery system that minimizes drug toxicity.
Angiogenesis is a key step in tumor growth and metastasis. The mechanism by which osteopontin (OPN) induces the angiogenesis of endothelial cells remains unclear. Here, we show that OPN confers cytoprotection through the activation of the PI3K/Akt pathway with subsequent upregulation of Bcl-xL and activation of nuclear factor-kappaB. OPN enhances the expression of vascular endothelial growth factor (VEGF) through the phosphorylation of AKT and extracellular signal-regulated kinase (ERK). In turn, OPN-induced VEGF activates PI3K/AKT and the ERK1/2 pathway as a positive feedback signal. Blocking the feedback signal by anti-VEGF antibody, PI3-kinase inhibitor or ERK inhibitor can partially inhibit the OPN-induced human umbilical vein endothelial cell (HUVEC) motility, proliferation and tube formation, while blocking the signal by anti-OPN or anti-alphavbeta3 antibody completely abrogates the biological effects of OPN on HUVECs. In addition, blood vessel formation is also investigated in vivo. The antiangiogenesis efficacy of anti-OPN antibody in vivo is more effective than that of anti-VEGF antibody, which only blocks the feedback signals. These data show that OPN enhances angiogenesis directly through PI3K/AKT- and ERK-mediated pathways with VEGF acting as a positive feedback signal. The results suggest that OPN might be a valuable target for developing novel antiangiogenesis therapy for treatment of cancer.
Here, a novel macroporous hydrogel dressing is presented that can accelerate wound healing and guard against bacteria-associated wound infection. Carboxymethyl agarose (CMA) is successfully prepared from agarose. The CMA molecular chains are cross-linked by hydrogen bonding to form a supramolecular hydrogel, and the hydroxy groups in the CMA molecules complex with Ag + to promote hydrogel formation. This hydrogel composite exhibits pH-responsiveness and temperature-responsiveness and releases Ag + , an antibacterial agent, over a prolonged period of time. Moreover, this hydrogel exhibits outstanding cytocompatibility and hemocompatibility. In vitro and in vivo investigations demonstrate that the hydrogel has enhanced antibacterial and anti-inflammatory capabilities and can significantly accelerate skin tissue regeneration and wound closure. Astonishingly, the hydrogel can cause the inflammation process to occur earlier and for a shorter amount of time than in a normal process. Given its excellent antibacterial, anti-inflammatory, and physicochemical properties, the broad application of this hydrogel in bacteriaassociated wound management is anticipated.
The poly-l-lysine-functionalized gold nanoparticle (PLL-GNP) was found to undergo reversible assembly/disassembly in the range of pH from 6.5 to 11.0 at room temperature. At a high pH value, the deprotonated
lysine residues allow the formation of α-helix and β-sheet structures at the expense of a part of random coil
and β-turn structures, thus inducing the assembly of GNPs. With a decrease of pH to 6.5, the assembly of
GNPs is disrupted due to the conversion of the α-helix and β-sheet back into the random and β-turn. It is
identified that the formation/collapse of an antiparallel β-sheet structure among PLL chains from adjacent
GNPs is responsible for reversible pH-dependent assembly/disassembly of GNPs. Since the conformation-induced assembly/disassembly process of the PLL-GNP can be well recognized by a shift of the surface
plasmon resonance band of the GNP and the color change of the solution, this study presents the possibility
of following the conformation change of a peptide by monitoring the spectral change of the GNP.
The management and treatment of tissue infection, especially chronic infection, represents a significant challenge. Application of autologous platelet-rich plasma (PRP) has emerged as a promising adjunct therapy for facilitating the healing of surgical wounds and tissue injuries. PRP is extracted from whole blood using a sequential centrifugation technique and when activated, can release a vast array of antimicrobial proteins, cytokines, and growth factors. These bioactive molecules are responsible for the ability of PRP to kill pathogens, resolve necrotic tissue, and promote wound healing. PRP is emerging as a useful supplement to prevent postoperative infection and treat chronic wound or bone infections. PRP displays a synergistic effect with antibiotics, which provides unique advantages when treating antibiotic-resistant bacteria. This review will describe the method for PRP preparation and its antibacterial properties, as well as discuss both preclinical in vivo results and evidence from clinical practice of PRP use for the treatment of wound and bone infections.
A cooperative dual-responsive polypeptide surface switching between superhydrophilic and superhydrophobic states is presented. This macroscopic phenomenon of surface originates from the combination of the cooperative unfolding/aggregation of the poly-L-lysine (PLL) immobilized on the substrate with micro/nanocomposite structure in response to pH and temperature. At pH lower than the pK(a) of PLL (approximately 11.0), PLL mainly adopts a random coil conformation, which corresponds to the superhydrophilic state on the rough surface substrate. Raising the pH to higher than the pK(a) allows the appearance of alpha-helix conformation, which also corresponds to the hydrophilic state. However, heating up the surface at pH higher than the pK(a) destabilizes the alpha-helix conformation and induces the formation of aggregated beta-sheet structures, which represents the superhydrophobic state. Lowering the pH and temperature simultaneously switches a reversible conversion from superhydrophobic to superhydrophilic states. In the switching process, the hydrophobicity and hydrophilicity can be "memorized" due to the cooperative pH and temperature stimuli-induced unfolding/aggregation behaviors of PLL. This provides a new exciting prospect for understanding surface properties of polypeptides and the design of smart material surfaces with potential applications in nanodevices, bioseparation, and biosensors.
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