An acid-responsive bone-targeting nanoplatform loaded with curcumin balances osteogenic and osteoclastic functions.

Postmenopausal osteoporosis (PMOP) is a predominant form of clinical osteoporosis. It has led to significant health and social burdens for older patients. Reestablishing the balance between osteogenic and osteoclastic is a crucial strategy for treating PMOP.

Transdermal Delivery of Baicalin Based on Bio-Vesicles and Its Efficacy in Antiaging of the Skin.

Objective: To develop a stable and efficient delivery system for baicalin, a flavonoid with potential antioxidant and antiaging properties, to overcome its limitations in solubility, stability, and skin permeability.

Methods: Baicalin was encapsulated using ATP synthase molecular motor technology into bio-vesicles derived from yeast/bacillus cell membranes, forming "motor baicalin" (MB). The liposome baicalin (LB), baicalin raw material (BRM), and bio-vesicles were used for comparison.

Autophagic cell death induced by pH modulation for enhanced iron-based chemodynamic therapy.

Iron-based chemodynamic therapy (CDT) exhibits commendable biocompatibility and selectivity, but its efficacy is constrained by the intracellular pH of tumors. To overcome this obstacle, we constructed a silica delivery platform loaded with autophagy-inducing reagents (rapamycin, RAPA) and iron-based Fenton reagents (FeO). This platform was utilized to explore a novel strategy that leverages autophagy to decrease tumor acidity, consequently boosting the effectiveness of CDT.

Nuclear-Targeted Nanostrategy Regulates Spatiotemporal Communication for Dual Antitumor Immunity.

Intercellular communication between tumor cells and immune cells regulates tumor progression including positive communication with immune activation and negative communication with immune escape. An increasing number of methods are employed to suppress the dominant negative communication in tumors such as PD-L1/PD-1. However, how to effectively improve positive communication is still a challenge.

Golgi Apparatus-Targeted Photodynamic Therapy for Enhancing Tumor Immunogenicity by Eliciting NLRP3 Protein-Dependent Pyroptosis.

Innate and adaptive immunity is important for initiating and maintaining immune function. The nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome serves as a checkpoint in innate and adaptive immunity, promoting the secretion of pro-inflammatory cytokines and gasdermin D-mediated pyroptosis. As a highly inflammatory form of cell death distinct from apoptosis, pyroptosis can trigger immunogenic cell death and promote systemic immune responses in solid tumors.

Engineering of copper sulfide mediated by phototherapy performance.

Copper sulfide based phototherapy, including photothermal therapy and photodynamic therapy, is an emerging minimally invasive treatment of tumor, which the light was converted to heat or reactive oxygen to kill the tumor cells. Compared with conventional chemotherapy and radiation therapy, Cu S based phototherapy is more efficient and has fewer side effects. However, considering the dose-dependent toxicity of Cu S, the performance of Cu S based phototherapy still cannot meet the requirement of the clinical application to now.

Sn species modified mesoporous zeolite TS-1 with oxygen vacancy for enzyme-free electrochemical HO detecting.

Sn species modified zeolite TS-1 with a unique mesopore structure (Sn-TS-1) and rich oxygen vacancy defects has been designed a sol-gel method and an ion-exchange process, which can be used as an enzyme-free electrochemical sensor for HO detection. The resultant composite Sn-TS-1 has a high BET surface area of 191 cm g, fast electron transfer, rich oxygen vacancies, and abundant active sites, showing super performance in HO reduction with a low detection limit (0.27 μM, S/N = 3).

forming oxygen/ROS-responsive niche-like hydrogel enabling gelation-triggered chemotherapy and inhibition of metastasis.

Though the development of the diverse hypoxia-activated prodrugs (HAPs) has made great progresses in the last several decades, current cancer therapy based on HAPs still suffers many obstacles, e.g., poor therapeutic outcome owing to hard deep reaching to hypoxic region, and the occurrence of metastasis due to hypoxia.

Macrophage-mediated delivery of magnetic nanoparticles for enhanced magnetic resonance imaging and magnetothermal therapy of solid tumors.

Magnetothermal therapy (MHT) has attracted significant attention due to the advantages of non-/minimal invasiveness, high efficiency, and excellent tissue penetration. However, developing small MHT agents (<50 nm) with excellent magnetothermal conversion performance and high tumor enrichment is a great challenge. Herein, a macrophage-mediated delivery of small Fe@FeO-DHCA nanoparticles (∼14 nm) was designed for enhanced magnetic resonance imaging (MRI) and MHT of solid tumors.

2D Cu-Bipyridine MOF Nanosheet as an Agent for Colon Cancer Therapy: A Three-in-One Approach for Enhancing Chemodynamic Therapy.

Chemodynamic therapy (CDT) is a highly tumor-specific and minimally invasive treatment that is widely used in cancer therapy. However, its therapeutic effect is limited by the poor efficiency of hydroxyl radical generation. In colon cancer in particular, the high expression of hydrogen sulfide (HS), which has strong reducibility, results in the consumption of generated hydroxyl radicals, further weakening the efficacy of CDT.

Precisely Targeted Nano-Controller of PD-L1 Level for Non-Small Cell Lung Cancer Spinal Metastasis Immunotherapy.

Although immune checkpoint inhibitors (ICIs) have been widely applied to treat non-small cell lung cancer (NSCLC), a significant proportion of patients, especially those with spinal metastasis (NSCLC-SM), are insensitive to anti-programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) ICIs. A drug delivery nano-controller of PD-L1 that targets NSCLC-SM can solve this problem, however, none have been developed to date. In this study, it is shown that integrin β3 (β3-int) is strongly upregulated in NSCLC-SM.

Hyaluronic acid-coated Bi:CuO: an HS-responsive agent for colon cancer with targeted delivery and enhanced photothermal performance.

Background: Endogenous hydrogen sulfide (HS)-responsive theranostic agents have attracted extensive attention due to their specificity for colon cancer. However, the development of such agents with high enrichment in tumors and excellent photothermal performance remains challenging.

Results: We prepared hyaluronic acid (HA)-coated Bi-doped cuprous oxide (Bi:CuO@HA) via a one-pot method.

An Endogenous HS-Activated Nanoplatform for Triple Synergistic Therapy of Colorectal Cancer.

Overproduced hydrogen sulfide (HS) is a highly potential target for precise colorectal cancer (CRC) therapy; herein, a novel 5-Fu/Cur-P@HMPB nanomedicine is developed by coencapsulation of the natural anticancer drug curcumin (Cur) and the clinical chemotherapeutic drug 5-fluorouracil (5-Fu) into hollow mesoporous Prussian blue (HMPB). HMPB with low Fenton-catalytic activity can react with endogenous HS and convert into high Fenton-catalytic Prussian white (PW), which can generate a high level of OH to activate chemodynamic therapy (CDT) and meanwhile trigger autophagy. Importantly, the autophagy can be amplified by Cur to induce autophagic cell death; moreover, Cur also acted as a specific chemosensitizer of the chemotherapy drug 5-Fu, achieving a good synergistic antitumor effect.

Siglec15 Checkpoint Blockade for Simultaneous Immunochemotherapy and Osteolysis Inhibition in Lung Adenocarcinoma Spinal Metastasis via a Hollow Nanoplatform.

Low responsiveness to anti-programmed death-1/programmed death-ligand 1 (anti-PD-1/PD-L1) for solid tumors indicates the presence of other immunosuppressive pathways. Siglec15, a newly discovered immune checkpoint, has been reported to repress immune responses in the tumor microenvironment (TME) and regulate osteoclast differentiation. However, the role of Siglec15 in the treatment for bone metastasis remains unclear.

Enhancement of anti-PD-1/PD-L1 immunotherapy for osteosarcoma using an intelligent autophagy-controlling metal organic framework.

Poor immunogenicity and compromised T cell infiltration impede the application of immune-checkpoint blockade (ICB) immunotherapy for osteosarcoma (OS). Although autophagy is involved in enhancing the immune response, the synergistic role of autophagy in ICB immunotherapy and the accurate control of autophagy levels in OS remain elusive and challenging. Here, we designed a pH-sensitive autophagy-controlling nanocarrier, CUR-BMS1166@ZIF-8@PEG-FA (CBZP), loading a natural derivative, curcumin (CUR), to boost the immunotherapeutic response of PD-1/PD-L1 blockade by activating immunogenic cell death (ICD) via autophagic cell death, and BMS1166 to inhibit the PD-1/PD-L1 interaction simultaneously, enhancing the tumor immunogenicity and sensitizing the antitumor T cell immunity.

Hypoxia-Induced Photogenic Radicals by Eosin Y for Efficient Phototherapy of Hypoxic Tumors.

The current reported photosensitizers generally show a decreased reactive oxygen species (ROS) generation property under hypoxia conditions, which is the main reason for the clinical failure of photodynamic therapy (PDT) in treatment of solid tumors. Herein, for the first time, hypoxia-induced photogenic radicals by eosin Y (Eos) were reported for efficient phototherapy of hypoxic tumors. More importantly, Eos shows a higher ROS and radical production efficiency under hypoxia conditions than under normoxia conditions.

A self-activating nanovesicle with oxygen-depleting capability for efficient hypoxia-responsive chemo-thermo cancer therapy.

Hypoxia-activated prodrugs (HAPs) promise to mitigate side effects of conventional chemotherapy and to enable precise medication treatment. One challenge facing HAPs-based chemotherapy is prodrug failure in normoxic tumor region. However, current strategies to enhance tumor hypoxia rely on delivery of oxygen-consuming agents and external stimulation, which can impede the optimal application of HAPs.

Disturbances of Dynamic Function in Patients With Bipolar Disorder I and Its Relationship With Executive-Function Deficit.

Abnormity in brain regional function and inter-regional cooperation have been linked with the dysfunction during cognitive and emotional processing in bipolar disorder (BD) patients. Recent evidences have suggested that brain function is not static but temporal dynamic. In present study, we aimed to characterize the temporal dynamics of regional function and inter-regional cooperation in BD and its relationship with executive dysfunction, an important deficit in BD.

An Imine-Linked Metal-Organic Framework as a Reactive Oxygen Species Generator.

A new metal-organic framework (MOF) with both coordination linkages and covalent linkages is prepared by coordinating Cu with pyrazolate for an aldehyde-functionalized trinuclear complex, and subsequent imine condensation with p-phenylenediamine, a reaction typical for covalent organic framework (COF) synthesis. This MOF×COF collaboration yields FDM-71 with honeycomb layers stacked in eclipsed fashion. After dissociating the Cu -pyrazolate coordination in FDM-71, the obtained organic components carry the information of structural defects, and thus vacancy identity (aldehyde-based unit vacancy and amine-based unit vacancy) and concentration are definitely resolved.

Microfluidics-Assisted Surface Trifunctionalization of a Zeolitic Imidazolate Framework Nanocarrier for Targeted and Controllable Multitherapies of Tumors.

Metal-organic framework (MOF)-based drug delivery nanosystems with both precise drug release and multidrug codelivery capabilities have emerged as promising candidates for cancer treatment. However, challenges are posed by the limited number of suitable payload types, uncontrollable drug leakage, and lack of chemical groups for postmodification. To overcome those challenges, we developed a core-shell nanocomposite composed of zeolitic imidazolate framework-90 (ZIF-90) coated with spermine-modified acetalated dextran (SAD) by a facile microfluidics-based nanoprecipitation method.

pH-responsive AgS nanodots loaded with heat shock protein 70 inhibitor for photoacoustic imaging-guided photothermal cancer therapy.

Heat-treated cancer cells have thermo-resistance due to the up-regulated levels of heat shock proteins (HSP) resulting in low therapeutic efficiency and ineffective ablation of tumors. In this work, we report pH-responsive AgS nanodots (AgS NDs) loaded with HSP70 inhibitor (QE-PEG-AgS) for enhanced photothermal cancer therapy. QE-PEG-AgS was easily prepared via self-assembly of hydrophobic AgS NDs, amphiphilic pH-responsive PEG-PAE polymer, and an HSP70 inhibitor quercetin (QE).

Detecting Basal Myeloperoxidase Activity in Living Systems with a Near-Infrared Emissive "Turn-On" Probe.

Detecting myeloperoxidase (MPO) activity in living organisms is important because MPO contributes to the pathogenesis of many diseases such as rheumatoid arthritis and other inflammatory diseases, artherosclerosis, neurodegenerative disease, and some cancers. However, rapid and effective methods for the detection of basal MPO activity in living systems have not yet been reported. Herein, we report a near-infrared (NIR) emissive "turn-on" probe that can specifically bind to MPO and accurately measure MPO activity in living cells and in vivo via a rapid response to initial hypochlorous acid (HOCl), produced by MPO.

Construction of microneedle-assisted co-delivery platform and its combining photodynamic/immunotherapy.

Despite advances in photodynamic therapy (PDT) for treating superficial tumor, the prospect of this monotherapy remains challenges in the context of systemic phototoxicity and poor efficacy. In this work, a physiologically self-degradable microneedle (MN)-assisted platform is developed for combining PDT and immunotherapy via controlled co-delivery of photosensitizer (PS) and checkpoint inhibitor anti-CTLA4 antibody (aCTLA4), which generates synergistic reinforcement outcome while reducing side effects. MN is composed of biocompatible hyaluronic acid integrated with the pH-sensitive dextran nanoparticles, which is fabricated to simultaneously encapsulate hydrophobic (Zinc Phthalocyanine) and hydrophilic agents (aCTLA4) via a double emulsion method.

FeO Mesocrystals with Distinctive Magnetothermal and Nanoenzyme Activity Enabling Self-Reinforcing Synergistic Cancer Therapy.

Magnetite (FeO) nanoparticles have been extensively used in noninvasive cancer treatment, for example, magnetic hyperthermia (MH) and chemodynamic therapy (CDT). However, how to achieve a highly efficient MH-CDT synergistic therapy based only on a single component of FeO still remains a challenge. Herein, hollow FeO mesocrystals (MCs) are constructed via a modified solvothermal method.

Design strategy of optical probes for tumor hypoxia imaging.

Clinical manifestations of tumors indicate that malignant phenotypes developing in the hypoxic microenvironment lead to resistance to cancer treatment, rendering chemotherapy, radiotherapy, and photodynamic therapy less sensitive and effective in patients with tumor. Visualizing the oxygen level in the tumor environment has garnered much attention due to its implications in precision tumor therapy. Following the rapid development of biomaterials in nanotechnology, various nanomaterials have been designed to visualize the oxygen levels in tumors.