Atherosclerosis (AS) is a leading cause of the life-threatening cardiovascular disease (CVD), creating an urgent need for efficient, biocompatible therapeutics for diagnosis and treatment. Biomimetic ...nanomedicines (bNMs) are moving closer to fulfilling this need, pushing back the frontier of nano-based drug delivery systems design. This review seeks to outline how these nanomedicines (NMs) might work to diagnose and treat atherosclerosis, to trace the trajectory of their development to date and in the coming years, and to provide a foundation for further discussion about atherosclerotic theranostics.
This review summerize various biomimetic nanomedicines for precise atherosclerosis diagnosis and treatment, which is vital for the development of atherosclerotic theranostic agents. Display omitted
Medication-related osteonecrosis of the jaw (MRONJ) is a serious complication associated with antiresorptive and antiangiogenic medications, of which impaired angiogenesis is a key pathological ...alteration. Since Magnesium (Mg)-based implants possess proangiogenic effects, we hypothesized that the biodegradable Mg implant could alleviate the development of MRONJ via enhancing angiogenesis.
MRONJ model was established and divided into the Veh + Ti group (Vehicle-treated rat, with Titanium (Ti) implant), BP + Ti group (Bisphosphonate (BP)-treated rat, with Ti implant), BP + Mg group (BP-treated rat, with Mg implant), BP + Mg + SU5416 group (BP-treated rat, with Mg implant and vascular endothelial growth factor (VEGF) receptor-2 inhibitor), BP + Mg + BIBN group (BP-treated rat, with Mg implant and calcitonin gene-related peptide (CGRP) receptor antagonist), and BP + Mg + SU5416+BIBN group (BP-treated rat, with Mg implant and VEGF receptor-2 inhibitor and CGRP receptor antagonist). The occurrence of MRONJ, alveolar bone necrosis, new bone formation and vessel formation were assessed by histomorphometry, immunohistochemistry, and micro-CT analysis.
Eight weeks after surgery, the BP + Mg group had significantly reduced occurrence of MRONJ-like lesion and histological osteonecrosis, increased bone microstructural parameters, and increased expressions of VEGFA and CGRP, than the BP + Ti group. By simultaneously blocking VEGF receptor-2 and CGRP receptor, the vessel volume and new bone formation in the BP + Mg group were significantly decreased, meanwhile the occurrence of MRONJ-like lesion and histological bone necrosis were significantly increased.
Biodegradable Mg implant could alleviate the development of MRONJ-like lesion, possibly via upregulating VEGF- and CGRP-mediated angiogenesis. Mg-based implants have the translational potential to be developed as a novel internal fixation device for patients with the risk of MRONJ.
This work reports a biodegradable Mg implant which ameliorates the development of MRONJ-like lesions possibly due to its angiogenic property. Mg-based implants have the potential to be developed as a novel internal fixation device for patients at the risk of MRONJ.
Most cellular elements could be functioned by forming aggregate structures through interactions with other molecules, which is like the luminescence mechanism of AIE molecules. However, in comparison ...to AIE molecules, the aggregation of biological elements appears to be more complex due to membership and mechanism, which is in line with the trend in biological evolution following the principle of simplicity to complexity. Here, we chose three distinctive examples because they differ significantly in their composition and show a progression from simple to complex, namely protein–protein complexes, protein–nucleic acid complexes, and protein–nucleic acid–lipid complexes. The majority of units that perform functions within cells belong to these three types. We discuss the formation mechanisms and related functions of the protein–protein complex (PML‐NB), the proteins–nucleic acids complex ribosome, and the proteins–nucleic acids–lipids complex exosome, and hope to provide expert insight for related fields.
The direction of evolution is from simple to complex. Most components in a cell are interdependent in their mode of action, aggregating into a complex structure to function. Research on different intracellular complexes will facilitate the prevention and treatment of various diseases. Here, protein aggregates PML‐NBs, protein‐nucleic acid aggregates ribosomes, and protein‐nucleic acid‐lipid aggregates exosomes are listed and discussed, respectively.
Antibiotic resistance is a global public health threat, and urgent actions should be undertaken for developing alternative antimicrobial strategies and approaches. Notably, bismuth drugs exhibit ...potent antimicrobial effects on various pathogens and promising efficacy in tackling SARS-CoV-2 and related infections. As such, bismuth-based materials could precisely combat pathogenic bacteria and effectively treat the resultant infections and inflammatory diseases through a controlled release of Bi ions for targeted drug delivery. Currently, it is a great challenge to rapidly and massively manufacture bismuth-based particles, and yet there are no reports on effectively constructing such porous antimicrobial-loaded particles. Herein, we have developed two rapid approaches (i.e., ultrasound-assisted and agitation-free methods) to synthesizing bismuth-based materials with ellipsoid- (Ellipsoids) and rod-like (Rods) morphologies respectively, and fully characterized physicochemical properties. Rods with a porous structure were confirmed as bismuth metal-organic frameworks (Bi-MOF) and aligned with the crystalline structure of CAU-17. Importantly, the formation of Rods was a ‘two-step’ crystallization process of growing almond-flake-like units followed by stacking into the rod-like structure. The size of Bi-MOF was precisely controlled from micro-to nano-scales by varying concentrations of metal ions and their ratio to the ligand. Moreover, both Ellipsoids and Rods showed excellent biocompatibility with human gingival fibroblasts and potent antimicrobial effects on the Gram-negative oral pathogens including Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Fusobacterium nucleatum. Both Ellipsoids and Rods at 50 μg/mL could disrupt the bacterial membranes, and particularly eliminate P. gingivalis biofilms. This study demonstrates highly efficient and facile approaches to synthesizing bismuth-based particles. Our work could enrich the administration modalities of metallic drugs for promising antibiotic-free healthcare.
•Two Bi particles were synthesized at room temperature in 30 min.•The rod-like particles (Rods) were confirmed as MOFs with crystallinity of CAU-17.•CAU-17 formation under ambient condition is a ‘two-steps’ crystallization process.•The as-synthesized Bi particles have potent antimicrobial and antibiofilm effects.
Medication-related osteonecrosis of the jaw (MRONJ) is a severe complication associated with antiresorptive medications managing osteoporosis, such as bisphosphonates (BPs). To date, there is very ...limited evidence from prospective, controlled studies to support or refute the controversial prevention regimen that if a discontinuation of BPs before dentoalveolar surgery, so called “drug holiday”, is effective in reducing the risk of MRONJ development in patients with osteoporosis. We proposed an experimental animal study, aiming to investigate the prevention of MRONJ following tooth extractions in osteoporotic condition, with the implementation of a BP drug holiday.
Twenty rats were subjected to bilateral ovariectomy. After establishing the osteoporotic condition, all rats were exposed to weekly injections of zoledronate acid (ZA) for 8 weeks. After ZA treatment, 10 rats were subjected to dental extraction and defined as control group, and the rest 10 rats assigned to the DH group had a drug holiday of 8 weeks prior to dental extraction. Eight weeks after the dentoalveolar surgery, bone turnover biomarker in serum, occurrence of MRONJ-like lesion and histomorphometric assessment of osteonecrosis in mandible, and bone microarchitecture indices in femur, were examined.
Eight weeks after dental extraction, the DH group showed a recovered osteoclastic activity, indicated by significantly increased number of osteoclasts in the mandibles and serum level of C-terminal telopeptides of type I collagen, as compared to the control group. No significant differences were observed in the gross-view and histological occurrences of MRONJ-like lesions between the two groups.
There was no significant difference in bone microarchitecture in the femur between the control and DH groups before ZA therapy and 8 weeks after dental extraction.
Our data provided the first experimental evidence in the osteoporotic animal model that the implementation of a BP holiday in prior to dental extractions could partially recover osteoclastic activity, but could not alleviate the development of MRONJ-like lesion or exacerbate the osteoporotic condition in the femur. Longer-term drug holiday, or combination of drug holiday and other prophylaxes to prevent MRONJ in patients with osteoporosis could be worth exploring in future studies, to pave the way for clinical managements.
This in vivo prospective study reported that a recovery of osteoclastic activity by a BP drug holiday for 8 weeks in osteoporosis rats did not alleviate the development of MRONJ-like lesion followed by dental extractions. It contributes to the understanding of regimens to prevent MRONJ.
Cisplatin is the first-line chemotherapeutic agent, but its systemic toxicity and side effects severely limit its clinical use. We report a microneedle technique to mediate the transdermal delivery ...of lipid-coated cisplatin nanoparticles (LCC-NPs) for efficient and safe cancer therapy. Cisplatin was encapsulated by tumor-targeting pH-responsive lipid nanoparticles with a high loading rate of 80%, and the encapsulation substantially increased the solubility of cisplatin and enhanced its antitumor efficiency in vitro. The LCC-NPs were embedded in dissolvable microneedles, and released from the microneedles after inserting into the skin. This enabled the nanoparticles to pass the stratum corneum for safe local delivery. An in vivo study with a xenograft tumor animal model demonstrated that microneedle arrays loaded with cisplatin nanoparticles significantly increased cytotoxicity and apoptosis in cancer cells with an apoptotic index of 58.6%, resulting in significantly reduced tumor volume and weight. Moreover, serum platinum, pulmonary toxicity, hepatotoxicity, and nephrotoxicity were not detected in vivo, indicating that this technique is biosafe. The cisplatin-nanoparticle microneedle system developed in this study may offer promising opportunities in cancer therapy for enhancing antitumor effects and reducing systemic toxicity and side effects.
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Timely and accurate assessment and diagnosis are extremely important and beneficial for all diseases, especially for some of the major human disease, such as cancers, cardiovascular ...diseases, infectious diseases, and neurodegenerative diseases. Limited by the variable disease microenvironment, early imperceptible symptoms, complex immune system interactions, and delayed clinical phenotypes, disease diagnosis and treatment are difficult in most cases. Molecular imaging (MI) techniques can track therapeutic drugs and disease sites in vivo and in vitro in a non-invasive, real-time and visible strategies. Comprehensive visual imaging and quantitative analysis based on different levels can help to clarify the disease process, pathogenesis, drug pharmacokinetics, and further evaluate the therapeutic effects. This review summarizes the application of different MI techniques in the diagnosis and treatment of these major human diseases. It is hoped to shed a light on the development of related technologies and fields.
PROteolysis TArgeting Chimeras (PROTACs), as a recently identified technique in the field of new drug development, provide new concepts for disease treatment and are expected to revolutionize drug ...discovery. With high specificity and flexibility, PROTACs serve as an innovative research tool to target and degrade disease-relevant proteins that are not currently pharmaceutically vulnerable to eliminating their functions by hijacking the ubiquitin-proteasome system. To date, PROTACs still face the challenges of low solubility, poor permeability, off-target effects, and metabolic instability. The combination of nanotechnology and PROTACs has been explored to enhance the
in vivo
performance of PROTACs regarding overcoming these challenging hurdles. In this review, we summarize the latest advancements in the building-block design of PROTAC prodrug nanoparticles and provide an overview of existing/potential delivery systems and loading approaches for PROTAC drugs. Furthermore, we discuss the current status and prospects of the split-and-mix approach for PROTAC drug optimization. Additionally, the advantages and translational potentials of carrier-free nano-PROTACs and their combinational therapeutic effects are highlighted. This review aims to foster a deeper understanding of this rapidly evolving field and facilitate the progress of nano-PROTACs that will continue to push the boundaries of achieving selectivity and controlled release of PROTAC drugs.
Schematic illustration of the combinational strategy of nanotechnology and PROTACs (Nano-PROTACs): the typical shortcomings of traditional PROTACs and the nanotechnology-based strategies for PROTAC drugs optimization.
In virtual environments, people tend to behave in line with the virtual avatars they embody. For example, when an individual embodies an attractive and physically fit avatar, they might show an ...increase in self-esteem. This phenomenon is called the Proteus effect. While prior research shows support for this effect with humanlike avatars, it is unclear whether non-humanlike avatars can also induce it. In this study, we examine the Proteus effect in the context of non-humanlike avatars and test whether the level of attractiveness of a non-humanlike avatar affects social participation. Two underlying mechanisms of the Proteus effect are considered: the mediating role of avatar identification and the moderating role of level of embodiment. To test our hypotheses, a 2 x 2 between-subjects lab experiment (N = 134) was conducted. Participants were randomly assigned to one of two non-humanlike avatars differing in level of attractiveness (attractive vs. unattractive) and one of two levels of embodiment (head-mounted display VR vs. desktop). The results showed that participants embodying the attractive non-humanlike avatar perceived higher levels of avatar identification via self-similarity, which increased social participation. Also, this study found that level of embodiment did not moderate the effect of attractiveness of the non-humanlike avatar on social participation.
•The study shows evidence for the Proteus effect in non-humanlike avatars•Embodying an attractive non-humanlike avatar is shown to drive social participation via self-similarity, but not via wishful identification•Level of embodiment does not moderate the effect of avatar attractiveness on social participation
Purpose
Methicillin-resistant
Staphylococcus aureus
(MRSA) infection at impaired wound is associated with high risks of developing to persistent bacterial infections since bacterial biofilm is easy ...to form in MRSA infected wounds. An advanced therapeutic approach to effectively penetrate and eliminate bacterial biofilm and to accelerate cell proliferation and migration at the wound is crucial.
Methods
The poly(ε-caprolactone)-monomethoxyl poly (ethylene glycol) (PCL-mPEG) micelles loaded with Quercetin and Rifampicin (QRMs) were prepared. Bacterial biofilm proliferation and elimination effect of QRMs were evaluated with confocal laser scanning microscopy. Antibacterial assay was further performed to detect antibacterial activity and mechanism. The cell scratch assay and cellular uptake were performed in HaCaT skin epithelial cells.
Results
Our results showed that the small sized QRMs could penetrate the interior of MRSA biofilm to disperse and eradicate biofilm. Then, antibiotics are released and accumulated in the acidic biofilm environment. QRMs could kill bacteria through increasing bacterial membrane permeability and altering membrane potential and membrane fluidity. Moreover, QRMs improved intracellular and cytoplasmic delivery efficiency of drugs to epithelial cells, and in the scratch test, presented a stronger ability to promote migration and proliferation of HaCaT cells compared with free drugs. Hemolysis test further proved good biocompatibility of QRMs.
Conclusions
QRMs could potentially be used as a novel dual-functional nanotherapeutic for anti-bacterial infection by eradicating biofilm and accelerating cells proliferation at MRSA infected wound.
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