Time and Space Dual-Blockade Strategy for Highly Invasive Nature of Triple-Negative Breast Cancer in Enhanced Sonodynamic Therapy Based on Fe-MOF Nanoplatforms.

Triple-negative breast cancer (TNBC), due to its high malignant degree and strong invasion ability, leads to poor prognosis and easy recurrence, so effectively curbing the invasion of TNBC is the key to obtaining the ideal therapeutic effect. Herein, a therapeutic strategy is developed that curbs high invasions of TNBC by inhibiting cell physiological activity and disrupting tumor cell structural function to achieve the time and space dual-blockade. The time blockade is caused by the breakthrough of the tumor-reducing blockade based on the ferroptosis process and the oxidation-toxic free radicals generated by enhanced sonodynamic therapy (SDT). Meanwhile, alkyl radicals from 2,2'-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride (AIPH) and 1 O2 attacked the organelles of tumor cells under ultrasound (US), reducing the physiological activity of the cells. The attack of free radicals on the cytoskeleton, especially on the proteins of F-actin and its assembly pathway, achieves precise space blockade of TNBC. The damage to the cytoskeleton and the suppression of the repair process leads to a significant decline in the ability of tumor cells to metastasize and invade other organs. In summary, the FTM@AM nanoplatforms have a highly effective killing and invasion inhibition effect on invasive TNBC mediated by ultrasound, showcasing promising clinical transformation potential.

In-depth occlusion of dentine tubules via the application of (poly-L-aspartic acid)­strontium and phosphate/fluoride to treat dentine hypersensitivity.

Dentine hypersensitivity (DH) is a common oral health issue and occlusion of the exposed dentinal tubules (DTs) is regarded as the most effective therapeutic treatment nowadays. However, it is still difficult to develop easy and effective strategies for deep occlusion of DTs. In this study, we develop a strategy for occluding DTs deeply and compactly via simple application of occlusion media including (poly-L-aspartic acid)­strontium (PAsp­strontium) and phosphate/fluoride. The bonding of strontium ions to poly-L-aspartic acid formed a positively charged PAsp­strontium complexes. After application of 15 min each, the PAsp­strontium and phosphate/fluoride rapidly penetrated into the DTs in turn via the electrostatic interaction, then occluded the DTs with crystals up to a depth of 150 µm. The occlusion within DTs was resistant to abrasive and acidic challenges. The occlusion media performed better than commercial desensitizers Duraphat and Gluma. Moreover, this strategy possessed sufficient biocompatible and excellent performance in vivo. The application of occlusion media would shed light on in the management of DH.

Polyelectrolyte-Cation Complexes Using PAsp-Sr Complexes Induce Biomimetic Mineralization with Antibacterial Ability.

Remineralized dentin with an antibacterial ability is still a significant challenge in dentistry. Previously, a polyelectrolyte-calcium complexes pre-precursor (PCCP) process is proposed for rapid collagen mineralization. In the present study, the expansion concept of the PCCP process is explored by replacing the calcium with other cations, such as strontium. The results of transmission electron microscopy (TEM), 3D stochastic optical reconstruction microscopy, energy-dispersive X-ray analysis, Fourier transform infrared spectroscopy, and high-resolution TEM with selected area electron diffraction demonstrate that biomimetic mineralization of collagen fibrils and demineralized dentin could be fulfilled with Sr&F-codoped hydroxyapatite (HAp) after they are treated with poly-aspartic acid-strontium (PAsp-Sr) suspension followed by a phosphate&fluoride solution. Moreover, dentin remineralized with Sr&F-codoped HAp exhibits in vitro and in vivo antibacterial ability against Streptococcus mutans. The cytotoxicity and oral mucosa irritation tests reveal excellent biocompatibility of mineralization mediums (PAsp-Sr suspension and phosphate&fluoride solution). The demineralized dentin's mechanical properties (elastic modulus and microhardness) could be restored almost to that of the intact dentin. Hence, the expansion concept of the PCCP process that replaces calcium ions with some cationic ions along with fluorine opens up new horizons for generating antibacterial remineralized dentin containing ions-doped HAp with excellent biocompatibility via biomimetic mineralization technology.

Gold Nanocage-Based Multifunctional Nanosensitizers for Programmed Photothermal /Radiation/Chemical Coordinated Therapy Guided by FL/MR/PA Multimodal Imaging.

Background: Radiotherapy is one of the main clinical methods for the treatment of malignant tumors at present. However, its application is limited by the radiation resistance of some tumor cells and the irradiation damage to the surrounding normal tissues, and the limitation of radiotherapy dose also affects the therapeutic effect. Therefore, developing diagnostic and therapeutic agents with imaging and radiosensitizing functions is urgently needed to improve the accuracy and efficacy of radiotherapy. Materials and Strategy: Herein, we synthesized multifunctional nanotheranostic FRNPs nanoparticles based on gold nanocages (GNCs) and MnO2 for magnetic resonance (MR)/photoacoustic (PA) imaging and combined photothermal, radiosensitive and chemical therapy. A programmed therapy strategy based on FRNPs is proposed. First, photothermal therapy is applied to ablate large tumors and increase the sensitivity of the tumor tissue to radiotherapy, then X-ray radiation is performed to further reduce the tumor size, and finally chemotherapeutic agents are used to eliminate smaller residual tumors and distant metastases. Results: As revealed by fluorescence, MR and PA imaging, FRNPs achieved efficient aggregation and retention at tumor sites of mice after intravenous injection. In vivo studies have shown that the programmed treatment of FRNPs-injected nude mice which were exposed to X-ray after 808 laser irradiation achieved the greatest inhibition of tumor growth compared with other treatment groups. Moreover, no obvious systemic toxicity was observed in all groups of mice, indicating the good biocompatibility of FRNPs and the safety of the treatment scheme. Conclusion: To sum up, our work not only showed a new radiosensitizer, but also provided a promising theranostic strategy for cancer treatment.

MnO2 Coated Mesoporous PdPt Nanoprobes for Scavenging Reactive Oxygen Species and Solving Acetaminophen-Induced Liver Injury.

As one of the most widely used drugs, acetaminophen, is the leading cause of acute liver injury. In addition, acetaminophen-induced liver injury (AILI) has a strong relationship with the overproduced reactive oxygen species, which can be effectively eliminated by nanozymes. To address these challenges, mesoporous PdPt@MnO2 nanoprobes (PPM NPs) mimicking peroxide, catalase, and superoxide dismutase-like properties are synthesized. They demonstrate nontoxicity, high colloidal stability, and exceptional reactive oxygen species (ROS)-scavenging ability. By scavenging excessive ROS, decreasing inflammatory cytokines, and inhibiting the recruitment and activation of monocyte/macrophage cells and neutrophils, the pathology mechanism of PPM NPs in AILI is confirmed. Moreover, PPM NPs' therapeutic effect and good biocompatibility may facilitate the clinical treatment of AILI.

Dental manifestations and treatment of hypophosphatemic rickets: A case report and review of literature.

BACKGROUND: The treatment and management of patients suffering from hypophosphatemic rickets (HR) remain a major challenge for dental practitioners and affected patients. OBJECTIVES: To report a case of HR presenting with specific dental findings and to review the dental manifestations and treatment of HR patients. METHODS: Case: A 32-year-old male presented with multiple dental abscesses and short stature. A thorough history was taken followed by clinical oral examination, and relevant radiological investigation was done. Literature research: In 2020, electronic literature searches were carried out in PubMed and complemented by a careful assessment of the reference lists of the identified relevant papers. Articles and reports fulfilled the inclusion criteria: indexed reviews, case series and case reports in English and restricted to human studies were considered. RESULTS: The intraoral examination revealed multiple dental abscesses and general periodontal disease; the radiographic examination showed poorly defined lamina dura, large pulp chambers and periapical lesions. Based on the contents of the 43 articles identified in the search, the current knowledge of dental manifestations, treatment and management of HR was summarized. CONCLUSIONS: As HR is a multisystem disease, multidisciplinary care is needed. By summarizing current evidences, we proposed an evidence-based dental management and provided recommendations on diagnosis and treatment of the disease. It is of profound clinical significance to acquire knowledge of the dental manifestations and provide optimal treatment options for patients.

Effects of an orthodontic primer containing amorphous fluorinated calcium phosphate nanoparticles on enamel white spot lesions.

OBJECTIVES: The study investigated the effects of an orthodontic primer containing amorphous fluorinated calcium phosphate (AFCP) nanoparticles on enamel white spot lesions (WSLs). MATERIALS AND METHODS: The AFCP nanoparticles were prepared and incorporated into Transbond XT Primer. Thirty-two human enamel slices were highly polished and randomly divided into four groups: no part covered (control), half covered with a primer containing 0 wt%, 25 wt%, and 35 wt% AFCP. Subsequently, samples were challenged by a modified pH-cycling and characterized by color measurement, micro-computed tomography, and scanning electron microscope (SEM). The bonding properties of the primers containing AFCP were assessed using shear bond strength test, and the mouse fibroblasts (L929) were employed to evaluate the cytotoxicity. RESULTS: When the enamel was challenged by pH cycling, 25 wt% and 35 wt% AFCP groups exhibited less color change (ΔE) and less mineral loss than the control and 0 wt% AFCP groups. The SEM images showed that the original microstructural integrity and mineral deposition rate of the enamel surface were better in the 25 wt% and 35 wt% AFCP groups. In particular, the 35 wt% AFCP group exhibited the best performance after 3 weeks of pH cycling. The shear bond strength and cell viability revealed no significant difference among the tested groups (P > 0.05). CONCLUSION: Using the primer containing 35 wt% AFCP might be a promising strategy for preventing the occurrence and development of WSLs during orthodontic treatment.

Structure design mechanisms and inflammatory disease applications of nanozymes.

Nanozymes are artificial enzymes with high catalytic activity, low cost, and good biocompatibility, and have received ever-increasing attention in recent years. Various inorganic and organic nanoparticles have been found to exhibit enzyme-like activities and are used as nanozymes for diverse biomedical applications ranging from tumor imaging and therapeutics to detection. However, their further clinical applications are hindered by the potential toxicity and long-term retention of nanomaterials in vivo. Clarifying the catalytic mechanism of nanozymes and identifying the key factors responsible for their behavior can guide the design of nanozyme structure, enlighten the ways to improve their enzyme-like activities, and minimize the dosage of nanozymes, leading to reduced toxicity to the human body for a real biomedical application prospect. In particular, inflammation occurring in numerous diseases is closely related to reactive oxygen species, and the active oxygen scavenging ability of nanozymes potentially exerts excellent therapeutic effects on inflammatory diseases. In this review, we systematically summarize the structure-activity relationship of nanozymes, including regulation strategies for size and morphology, surface structure, and composition. Based on the structure-activity mechanisms, a series of chemically designed nanozymes developed to target various inflammatory diseases are briefly summarized.

Topology optimization based deterministic lateral displacement array design for cell separation.

Circulating tumor cell (CTC) can be used to guide cancer theranostics. How to isolate efficiently CTCs from blood owns great clinical requirement. Deterministic lateral displacement (DLD) is a pillar-array-based effective passive microfluidic method to separate cells based on their sizes. DLD is a potential CTC isolation tool. Pillar shape is one of the key priorities in DLD array design. Altered zigzag mode is a normally undesired phenomenon that leads zigzag particles away from flow direction. This work makes use of the altered zigzag mode to manipulate zigzag particles for the first time, and developed a novel DLD chip with topology optimized pillar shape and a wide DLD channel. The novel designing method based on topology optimization (TO) greatly increases lateral displacement of different sized cells, meanwhile demonstrates its universality and expansibility. The proposed structure has the ability to shorten the device and to manipulate cells flexibly. Bead experiment has been applied to determine the critical diameter of the DLD array. Numerical, bead and cell experiment have been carried out to verify the separation efficiency of the structure. The TO-based wide DLD channel promotes the separation efficiency.