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The clinical utility of small-diameter vascular grafts (SDVGs) is limited due to the possibility of thrombosis and intimal hyperplasia. These features can delay the development of a functional endothelial cell (EC) monolayer on the luminal surface of grafts. Therefore, the development and fabrication of vascular grafts (VGs) with comparable extracellular matrix (ECM) functions are mandatory to elicit hemocompatible confluent EC monolayers, and angiogenesis behavior inside the body. To promote the interactions between ECs and the surface of electrospun polyacrylic acid-grafted polyhedral oligomeric silsesquioxane-poly(carbonate-urea)-urethane (PAAc-POSS-PCUU), in this research, the surface of nanofibers was modified by covalently immobilizing extracted soluble proteins from aorta (ESPA) using EDC/NHS chemistry. The ATR-FTIR spectroscopy, WCA, and SEM microscopy confirmed the binding of acrylic acid and soluble vascular proteins on the surface of electrospun fibers. The PAAc-POSS-PCUU nanofibers and engineered biomimetic Pro-PAAc-POSS-PCUU nanofibers exhibited excellent biocompatibility indicated by increased survival rate (p < 0.05). Western blotting revealed the increase of VE-cadherin, Tie-2, vWF, and VEGFR-2 in HUVECs after being plated on PAAc-POSS-PCUU and Pro-PAAc-POSS-PCUU scaffolds, indicating appropriate angiogenesis behavior (p < 0.05). Besides, the antioxidant capacity was induced by the increase of SOD and GPx activity (p < 0.05). Additionally, blood compatibility tests revealed that Pro-PAAc-POSS-PCUU nanofibers accelerate the formation of a single EC layer without hemolysis and platelet adhesion. Taken together, Pro-PAAc-POSS-PCUU nanofibers exhibited excellent blood compatibility, and angiogenesis behavior, making them a promising candidate for clinical applications., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Photoimmunotherapy represents an innovative approach to enhancing the efficiency of immunotherapy in cancer treatment. This approach involves the fusion of immunotherapy and phototherapy (encompassing techniques like photodynamic therapy (PDT) and photothermal therapy (PTT)). Boron-dipyrromethene (BODIPY) has the potential to trigger immunotherapy owing to its excellent PD and PT efficiency. However, the improvements in water solubility, bioavailability, PD/PT combined efficiency, and tumor tissue targeting of BODIPY require introduction of suitable carriers for potential practical application. Herein, a disulfide bond-based hollow mesoporous organosilica (HMON) with excellent biocompatibility and GSH-responsive degradation properties was used as a carrier to load a bithiophene Aza-BODIPY dye (B5), constructing a sample chemotherapy reagent-free B5@HMON nanoplatform achieving triple-synergistic photoimmunotherapy. HMON, involving disulfide bond, is utilized to improve water solubility, tumor tissue targeting, and PD efficiency by depleting GSH and enhancing host-guest interaction between B5 and HMO. The study reveals that HMON's large specific surface area and porous properties significantly enhance the light collection and oxygen adsorption capacity. The HMON's rich mesoporous structure and internal cavity achieved a loading rate of B5 at 11 %. It was found that the triple-synergistic nanoplatform triggered a stronger anti-tumor immune response, including tumor invasion, cytokine production, calreticulin translocation, and dendritic cell maturation, eliciting specific tumor-specific immunological responses in vivo and in vitro. The BALB/c mouse model with 4T1 tumors was used to assess tumor suppression efficiency in vivo, showing that almost all tumors in the B5@HMON group disappeared after 14 days. Such a simple chemotherapy reagent-free B5@HMON nanoplatform achieved triple-synergistic photoimmunotherapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Investigating the interactions between nanomaterials and the cells they are likely to encounter in vivo is a critical aspect of designing nanomedicines for imaging and therapeutic applications. Immune cells such as dendritic cells, macrophages, and myeloid derived suppressor cells have a frontline role in the identification and removal of foreign materials from the body, with interactions shown to be heavily dependent on variables such as nanoparticle size, charge, and surface chemistry. Interactions such as cellular association or uptake of nanoparticles can lead to diminished functionality or rapid clearance from the body, making it critical to consider these interactions when designing and synthesizing nanomaterials for biomedical applications ranging from drug delivery to imaging and biosensing. We investigated the interactions between PEGylated organosilica nanoparticles and naturally endocytic immune cells grown from stem cells in murine bone marrow. Specifically, we varied the particle size from 60 nm up to 1000 nm and investigated the effects of size on immune cell association, activation, and maturation with these critical gatekeeper cells. These results will help inform future design parameters for in vitro and in vivo biomedical applications utilizing organosilica nanoparticles.

An intelligent delivery nanoformulation could enhance the utilization efficacy, uptake, and translocation of pesticides in plants. Herein, a redox/pH-triggered and fluorescent smart delivery nanoformulation was designed and constructed by using hollow mesoporous organosilica nanoparticles (HMONs) and ZnO quantum dots as the nanocarrier and capping agent, respectively. Boscalid was further loaded to generate Boscalid@HMONs@ZnO with a loading rate of 9.8% for controlling Botrytis cinerea ( B. cinerea ). The quantity of boscalid released by Boscalid@HMONs@ZnO in a glutathione environment or at pH 3.0 was 1.3-fold and 1.9-fold higher than that in a neutral condition. Boscalid@HMONs@ZnO has 1.7-fold the toxicity index of boscalid technical against B. cinerea in antifungal experiments. Pot experiments revealed that the efficacy of Boscalid@HMONs@ZnO was significantly enhanced more than 1.27-fold compared to commercially available water-dispersible granules of boscalid. Due to the fluorescence properties of Boscalid@HMONs@ZnO, pesticide transport's real-time monitoring of pesticide translocation in tomato plants could be observed by confocal laser scanning microscopy. Fluorescence images revealed that HMONs@ZnO had been effectively transported via treated leaves or roots in tomato plants. This research showed the successful application of HMONs@ZnO as a nanocarrier for controlling disease and offered an effective avenue to explore the real-time tracking of pesticide translocation in plants.

In this work, a polyhedral silsesquioxane (POSS) was used as an engineered drug delivery system for two oxindolimine-copper(II) anticancer complexes, [Cu(isaepy)] + and [Cu(isapn)] + . The interest in hybrid POSS comes from the necessity of developing materials that can act as adjuvants to improve the cytotoxicity of non-soluble metallodrugs. Functionalization of POSS with a triazole ligand (POSS-atzac) permitted the anchorage of such copper complexes, producing hybrid materials with efficient cytotoxic effects. Structural and morphological characterizations of these copper-POSS systems were performed by using different techniques (IR, NMR, thermogravimetric analysis). A combination of continuous-wave (CW) and pulsed EPR (HYSCORE) spectroscopies conducted at the X-band have enabled the complete characterization of the coordination environment of the copper ion in the POSS-atzac matrix. Additionally, the cytotoxic effects of the loaded materials, [Cu(isapn)]@POSS-atzac and [Cu(isaepy)]@POSS-atzac, were assessed toward melanomas (SK-MEL), in comparison to non-tumorigenic cells (fibroblast P4). Evaluation of their nuclease activity or ability to facilitate cleavage of DNA indicated concentrations as low as 0.6 μg mL -1 , while complete DNA fragmentation was observed at 25 μg mL -1 . By using adequate scavengers, investigations on active intermediates responsible for their cytotoxicity were performed, both in the absence and in the presence of ascorbate as a reducing agent. Based on the observed selective cytotoxicity of these materials toward melanomas, investigations on the reactivity of these complexes and corresponding POSS-materials with melanin, a molecule that contributes to melanoma resistance to chemotherapy, were carried out. Results indicated the main role of the binuclear copper species, formed at the surface of the silica matrix, in the observed reactivity and selectivity of these copper-POSS systems.

Developing strategies to target injured pancreatic acinar cells (PACs) in conjunction with primary pathophysiology-specific pharmacological therapy presents a challenge in the management of acute pancreatitis (AP). We designed and synthesized a trypsin-cleavable organosilica precursor bridged by arginine-based amide bonds, leveraging trypsin's ability to selectively identify guanidino groups on arginine via Asp189 at the active S1 pocket and cleave the carboxy-terminal (C-terminal) amide bond via catalytic triads. The precursors were incorporated into the framework of mesoporous silica nanoparticles (MSNs) for encapsulating the membrane-permeable Ca 2+ chelator BAPTA-AM with a high loading content (∼43.9%). Mesenchymal stem cell membrane coating and surface modification with PAC-targeting ligands endow MSNs with inflammation recruitment and precise PAC-targeting abilities, resulting in the highest distribution at 3 h in the pancreas with 4.7-fold more accumulation than that of naked MSNs. The outcomes transpired as follows: After bioinspired MSNs' skeleton biodegradation by prematurely and massively activated trypsin, BAPTA-AM was on-demand released in injured PACs, thereby effectively eliminating intracellular calcium overload (reduced Ca 2+ level by 81.3%), restoring cellular redox status, blocking inflammatory cascades, and inhibiting cell necrosis by impeding the IκBα/NF-κB/TNF-α/IL-6 and CaMK-II/p-RIP3/p-MLKL/caspase-8,9 signaling pathways. In AP mice, a single dose of the formulation significantly restored pancreatic function (lipase and amylase reduced more by 60%) and improved the survival rate from 50 to 91.6%. The formulation offers a potentially effective strategy for clinical translation in AP treatment.

The thioredoxin system is involved in cancer development and therefore is a promising target for cancer chemotherapy. Thioredoxin reductase (TrxR) is a key component of the thioredoxin (Trx) system, and is overexpressed in many cancers to inhibit apoptosis-related proteins. Alternatively, inhibition of thioredoxin reductase and upregulation of apoptosis factors provide a therapeutic strategy for anti-tumor treatment. In this study, an ultrasound-activatable meso -organosilica nanomedicine was prepared by integrating chloroquine (CQ) into hollow mesoporous organosilica (CQ@MOS). The meso -organosilica nanomedicine can inhibit the activity of thioredoxin reductase, elevate cellular reactive oxygen species (ROS) levels, upregulate the pro-apoptotic factors in the c-Jun N-terminal kinase (JNK) apoptosis pathway and induce autophagy inhibition, further resulting in mitochondrial membrane potential (MMP) depolarization and cellular ATP content decrease, ultimately causing significant damage to tumor cells. Moreover, CQ@MOS can efficiently deliver chloroquine into cancer cells and promote an enhanced sonodynamic effect for effective anti-tumor chemotherapy and sonodynamic therapy. This study may enlighten us on a new anti-tumor strategy and suggest its promising applications in cancer treatments.

Allergic diseases are immune system dysfunctions mediated by mast cell (MC) activation stimulated by specific allergens. However, current small molecular MC stabilizers for allergic disease prevention often require multiple doses over a long period of time and are associated with serious side effects. Herein, we develop a diselenide-bridged mesoporous silica nanostabilizer, proving that it could specifically target sensitized MCs via the recognition of IgE aptamer and IgE. Meantime, the IgE aptamer can also mitigate allergic reactions by preventing re-exposure of allergens from the surface of sensitized MCs. Furthermore, the diselenide-bridged scaffold can be reduced by the intracellular excessive ROS, subsequently achieving redox homeostasis via ROS depletion. Finally, the precise release of small molecular MC stabilizers along with the biodegradation of nanocarrier can stabilize the membranes of MCs. In vivo assays in passive cutaneous anaphylactic (PCA) and allergic rhinitis (AR) mice indicated that our current strategy further endowed it with a high efficacy, long-term therapeutic time window, as well as negligible inflammatory side effects for allergic diseases, offering a promising therapeutic strategy for the clinical generalization of allergic diseases.

Understanding of the interactions between macrophages and multifunctional nanoparticles is important for development of novel macrophage-based immunotherapies. Here, we investigated the effects of fluorescent thiol-organosilica particle size and surface properties on cell-particle interactions, including mitochondrial activity, using the mouse macrophage cell line J774A.1. Three different sizes of thiol-organosilica particles (150, 400, and 680 nm in diameter) containing fluorescein (OS/F150, OS/F400, and OS/F680) and particles surface functionalized with polyethylenimine (PEI) (OS/F150PEI, OS/F400PEI, and OS/F680PEI) were prepared. Flow cytometric analysis, time-lapse imaging, and single-cell analysis of particle uptake and mitochondrial activity of J774A.1 cells demonstrated variations in uptake and kinetics depending on the particle size and surface as well as on each individual cell. Cells treated with OS/F150 and OS/F150PEI showed higher uptake and mitochondrial activity than those treated with other particles. The interaction between endosomes and mitochondria was observed using 3D fluorescent imaging and was characterized by the involvement of iron transport into mitochondria by iron-containing proteins adsorbed on the particle surface. Scanning electron microscopy of the cells treated with the particles revealed alterations in cell membrane morphology, depending on particle size and surface. We performed correlative light and electron microscopy combined with time-lapse and 3D imaging to develop an integrated correlation analysis of particle uptake, mitochondrial activity, and cell membrane morphology in single macrophages. These cell-specific characteristics of macrophages against functional particles and their evaluation methods are crucial for understanding the immunological functions of individual macrophages and developing novel immunotherapies.

A promising therapeutic strategy in cancer treatment merges photodynamic therapy (PDT) induced apoptosis with ferroptosis, a form of programmed cell death governed by iron-dependent lipid peroxidation. Given the pivotal role of mitochondria in ferroptosis, the development of photosensitizers that specifically provoke mitochondrial dysfunction and consequentially trigger ferroptosis via PDT is of significant interest. To this end, we have designed and synthesized a novel nanoparticle, termed FECTPN, tailored to address this requisite. FECTPN harnesses a trifecta of critical attributes: precision mitochondria targeting, photoactivation capability, pH-responsive drug release, and synergistic apoptosis-ferroptosis antitumor treatment. This nanoparticle was formulated by conjugating an asymmetric silicon phthalocyanine, Chol-SiPc-TPP, with the ferroptosis inducer Erastin onto a ferritin. The Chol-SiPc-TPP is a chemically crafted entity featuring cholesteryl (Chol) and triphenylphosphine (TPP) functionalities bonded axially to the silicon phthalocyanine, enhancing mitochondrial affinity and leading to effective PDT and subsequent apoptosis of cells. Upon cellular uptake, FECTPN preferentially localizes to mitochondria, facilitated by Chol-SiPc-TPP's targeting mechanics. Photoactivation induces the synchronized release of Chol-SiPc-TPP and Erastin in the mitochondria's alkaline domain, driving the escalation of both ROSs and lipid peroxidation. These processes culminate in elevated antitumor activity compared to the singular application of Chol-SiPc-TPP-mediated PDT. A notable observation is the pronounced enhancement in glutathione peroxidase-4 (GPX4) expression within MCF-7 cells treated with FECTPN and subjected to light exposure, reflecting intensified oxidative stress. This study offers compelling evidence that FECTPN can effectively induce ferroptosis and reinforces the paradigm of a synergistic apoptosis-ferroptosis pathway in cancer therapy, proposing a novel route for augmented antitumor treatments., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A persistent inflammatory response, intrinsic limitations in axonal regenerative capacity, and widespread presence of extrinsic axonal inhibitors impede the restoration of motor function after a spinal cord injury (SCI). A versatile treatment platform is urgently needed to address diverse clinical manifestations of SCI. Herein, we present a multifunctional nanoplatform with anisotropic bimodal mesopores for effective neural circuit reconstruction after SCI. The hierarchical nanoplatform features of a Janus structure consist of dual compartments of hydrophilic mesoporous silica (mSiO 2 ) and hydrophobic periodic mesoporous organosilica (PMO), each possessing distinct pore sizes of 12 and 3 nm, respectively. Unlike traditional hierarchical mesoporous nanomaterials with dual-mesopores interlaced with each other, the two sets of mesopores in this Janus nanoplatform are spatially independent and possess completely distinct chemical properties. The Janus mesopores facilitate controllable codelivery of dual drugs with distinct properties: the hydrophilic macromolecular enoxaparin (ENO) and the hydrophobic small molecular paclitaxel (PTX). Anchoring with CeO 2 , the resulting mSiO 2 &PMO-CeO 2 -PTX&ENO nanoformulation not only effectively alleviates ROS-induced neuronal apoptosis but also enhances microtubule stability to promote intrinsic axonal regeneration and facilitates axonal extension by diminishing the inhibitory effect of extracellular chondroitin sulfate proteoglycans. We believe that this functional dual-mesoporous nanoplatform holds significant potential for combination therapy in treating severe multifaceted diseases.

Background: Chemotherapy, the mainstay treatment for metastatic cancer, presents serious side effects due to off-target exposure. In addition to the negative impact on patients' quality of life, side effects limit the dose that can be administered and thus the efficacy of the drug. Encapsulation of chemotherapeutic drugs in nanocarriers is a promising strategy to mitigate these issues. However, avoiding premature drug release from the nanocarriers and selectively targeting the tumour remains a challenge., Results: In this study, we present a pioneering method for drug integration into nanoparticles known as mesoporous organosilica drugs (MODs), a distinctive variant of periodic mesoporous organosilica nanoparticles (PMOs) in which the drug is an inherent component of the silica nanoparticle structure. This groundbreaking approach involves the chemical modification of drugs to produce bis-organosilane prodrugs, which act as silica precursors for MOD synthesis. Mitoxantrone (MTO), a drug used to treat metastatic breast cancer, was selected for the development of MTO@MOD nanomedicines, which demonstrated a significant reduction in breast cancer cell viability. Several MODs with different amounts of MTO were synthesised and found to be efficient nanoplatforms for the sustained delivery of MTO after biodegradation. In addition, Fe 3 O 4 NPs were incorporated into the MODs to generate magnetic MODs to actively target the tumour and further enhance drug efficacy. Importantly, magnetic MTO@MODs underwent a Fenton reaction, which increased cancer cell death twofold compared to non-magnetic MODs., Conclusions: A new PMO-based material, MOD nanomedicines, was synthesised using the chemotherapeutic drug MTO as a silica precursor. MTO@MOD nanomedicines demonstrated their efficacy in significantly reducing the viability of breast cancer cells. In addition, we incorporated Fe 3 O 4 into MODs to generate magnetic MODs for active tumour targeting and enhanced drug efficacy by ROS generation. These findings pave the way for the designing of silica-based multitherapeutic nanomedicines for cancer treatment with improved drug delivery, reduced side effects and enhanced efficacy., (© 2024. The Author(s).)

Myopia is a global public health issue. Rigid contact lenses (RCLs) are an effective way to correct or control myopia. However, bioadhesion issues remain one of the significant obstacles limiting its clinical application. Although enhancing hydrophilicity through various surface treatments can mitigate this problem, the duration of effectiveness is short-lived and the processing involved is complex and costly. Herein, an antiadhesive RCLs material was designed via 8-armed methacrylate-POSS (8MA-POSS), and poly(ethylene glycol) methacrylate (PEGMA) copolymerization with 3-[tris(trimethylsiloxy)silyl] propyl methacrylate (TRIS). The POSS and PEG segments incorporated P(TRIS- co -PEGMA- co -8MA-POSS) (PTPM) material was obtained and their optical transparency, refractive index, resolution, hardness, surface charge, thermal features, and wettability were tested and optimized. The antibioadhesion activities, including protein, lipid, and bacteria, were evaluated as well. In vitro and in vivo results indicated that the optimized antibioadhesive PTPM materials present good biocompatibility and biosafety. Thus, such POSS and PEG segments containing material were a potential antibioadhesive RCL material option.

Wound healing is a dynamic and complex process, it's urgent to develop new wound dressings with excellent performance to promote wound healing at the different stages. Here, a novel composite hydrogel dressing composed by silver nanoparticles (AgNPs) impregnated adenine-modified chitosan (CS-A) and octafunctionalized polyhedral oligomeric silsesquioxane (POSS) of benzaldehyde-terminated polyethylene glycol (POSS-PEG-CHO) solution was presented to solve the problem of wound infection. Modification of chitosan with adenine, not only can improve the water solubility of chitosan, but also introduce bioactive substances to promote cell proliferation. CS-A and POSS-PEG-CHO were cross-linked by Schiff-base reaction to form the injectable self-healing hydrogel. On this basis, AgNPs were added into the hydrogel, which endows the hydrogel with better antibacterial activity. Moreover, this kind of hydrogel exhibits excellent cell proliferation properties. Studies demonstrated that the hydrogel can significantly accelerate the closure of infected wounds. The histological analysis and immunofluorescence staining demonstrated that the wounds treated with the composite hydrogel exhibited fewer inflammatory cells, more collagen deposition and angiogenesis, faster regeneration of epithelial tissue. Above all, adenine-modified chitosan composite hydrogel with AgNPs loaded was considered as a dressing material with great application potential for promoting the healing of infected wounds., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Cuifen Lu reports financial support was provided by Education Department of Hubei Province. Cuifen Lu reports a relationship with Hubei University that includes: employment., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study demonstrates the potential of sono-photodynamic therapy as an effective approach for enhancing singlet oxygen generation using the synthesized Schiff-base diaxially substituted silicon phthalocyanines. In photochemical studies, the singlet oxygen quantum yields (Φ ∆ ) were determined as 0.43 for Si1a, 0.94 for Q-Si1a, 0.58 for S-Si1a, and 0.49 for B-Sia1. In sono-photochemical studies, the Φ ∆ values were reached to 0.67 for Si1a, 1.06 for Q-Si1a, 0.65 for S-Si1a, and 0.67 for B-Sia1. In addition, this study demonstrates the therapeutic efficacy of phthalocyanines synthesized as sensitizers on the PC3 prostate cancer cell line through in vitro experiments. The application of these treatment modalities exhibited notable outcomes, leading to a substantial decrease in cell viability within the PC3 prostate cancer cell line. These findings highlight the potential of utilizing these synthesized phthalocyanines as promising therapeutic agents for prostate cancer treatment., (© 2024. The Author(s).)

To investigate the renal protective effects of the polysaccharide LEP-1a and derivatives of selenium (SeLEP-1a) from Lachnum YM38, cisplatin (CP) was used to establish an acute kidney model. LEP-1a and SeLEP-1a could effectively reverse the decrease in renal index and improved renal oxidative stress. LEP-1a and SeLEP-1a significantly reduced the contents of the inflammatory cytokines. They could inhibit the release of cyclooxygenase 2 (COX-2) and nitric oxide synthase (iNOS) and increase the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and hemeoxygenase-1 (HO-1). At the same time, the PCR results indicated that SeLEP-1a could significantly inhibit the mRNA expression levels of toll-like receptor 4 (TLR4), nuclear factor-kB (NF-κB) p65 and inhibitor of kappa B-alpha (IκBα). Western blot analysis showed that LEP-1a and SeLEP-1a significantly downregulated the expression levels of Bcl-2-associated X protein (Bax) and cleaved caspase-3 and upregulated phosphatidylinositol 3-kinase (p-PI3K), protein kinase B (p-Akt) and B-cell lymphoma 2 (Bcl-2) protein expression levels in the kidney. LEP-1a and SeLEP-1a could improve CP-induced acute kidney injury by regulating the oxidative stress response, NF-κB-mediated inflammation and the PI3K/Akt-mediated apoptosis signalling pathway., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Background: The respiratory system is intensely damaged by acute lung injury (ALI). The anti-inflammatory effects of tetramethylpyrazine (TMP) against ALI have been confirmed, but it exhibits a short half-life. miR-194-5p could directly target Rac1, but the internalization rate of miRNA cells was low., Purpose: To explore the potential of the soft mesoporous organic silica nanoplatform (NPs) as carriers for delivery of TMP and miR-194-5p through the tail vein., Methods: NPs@TMP and NPs@PEI@miR-194-5p were added to the HUVEC cell-lines, in vitro, to observe the cell uptake and cytotoxic effects. In vivo experiments were conducted by injecting fluorescently labeled NPs through the tail vein and tracking distribution. Therapeutic and toxic side-effects were analyzed systemically., Results: In vitro study exhibited that NPs have no toxic effect on HUVECs within the experimental parameters and have excellent cellular uptake. The IVIS Spectrum Imaging System shows that NPs accumulate mainly in the lungs. NPs@TMP treatment can improved oxidative stress and inflammation levels in ALI mice and inhibited the TLR4/NLRP3/caspase 1 pathway. NPs@PEI@miR-194-5p can inhibit the Rac1/ZO-1/occludin pathway and improved endothelial cell permeability in ALI mice. The co-treatment of NPs@TMP and NPs@PEI@miR-194-5p can significantly improved the survival rates of the mice, reduced pulmonary capillary permeability and improved pathological injury in ALI mice., Innovation: This study combined traditional Chinese medicine, bioinformatics, cellular molecular biology and nanobiomedicine to study the pathogenesis and treatment of ALI. The rate of cellular internalization was improved by changing the shape and hardness of nanoparticles. NPs@TMP and NPs@PEI@miR-194-5p combined application can significantly improve the survival condition and pathological injury of mice., Conclusion: NPs loaded with TMP and miR-194-5p showed a greater therapeutic effect in ALI mice., Competing Interests: This research was conducted without any commercial or financial relationships that could be construed as potential conflicts of interest., (© 2023 Min et al.)

Metal ions have active roles in biochemical, industrial, and environmental processes. The design and development of new rapid sensing materials with advanced reasonable, compelling, and convenient, techniques are urgent. Here in this work, we design and develop sensor with the facile amalgamation of the pyrene-based organosilane (5) through a click silylation approach silicon composite for selective detection of Cu 2+ ions. Physicochemical and keen methods are employed to perceive the resultant hybrid nanoparticles (H-NPs), and these nanocomposites similarly displayed a strong affection for Cu 2+ ions. In addition, the identification restrictions while utilizing 5 and H-NP's towards Cu 2+ found in this study are far lower than the WHO rules for drinking water. Further, organosilane (5) shows good antibacterial and antioxidant activity. The antibacterial effects of triazole-based organosilane (5), are evaluated with a molecular docking study with Escherichia coli (IJZQ) was conducted. The selected ligand was revealed to have a reasonable docking score with a binding energy of -8.40 kcal mol -1 ., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In this study, three new axially disubstituted silicon phthalocyanines (SiPc1-3) and their quaternized phthalocyanine derivatives (QSiPc1-3) were prepared and characterized. The biological properties (antioxidant, antimicrobial, antibiofilm, and microbial cell viability activities) of the water-soluble silicon phthalocyanines were examined, as well. A 1 % DMSO diluted with pure water was used as a solvent in biological activity studies. All the compounds exhibited high antioxidant activity. They displayed efficient antimicrobial and antimicrobial photodynamic therapeutic properties against various microorganisms, especially Gram (+) bacteria. Additionally, they demonstrated high antibiofilm activities against S. aureus and P. aeruginosa. In addition, 100 % bacterial reduction was obtained for all the studied phthalocyanines against E. coli viable cells. Besides, the DNA cleavage and binding features of compounds (QSiPc1-3) were studied using pBR322 DNA and CT-DNA, respectively. Furthermore, the human topoisomerase I enzyme inhibition activities of compounds QSiPc1-3 were studied. Anticancer properties of the water-soluble compounds were investigated using cell proliferation MTT assay. They exhibited anticarcinogenic activity against the human colon cancer cell line (DLD-1). Compounds QSiPc1 and QSiPc3 displayed a high anticarcinogenic effect on the DLD-1 cell line. The obtained results indicated that all the studied compounds may be effective biological agents and anticancer drugs after further investigations., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

A major challenge to the treatment of advanced prostate cancer (PCa) is the development of resistance to androgen-deprivation therapy (ADT) and chemotherapy. It is imperative to discover effective therapies to overcome drug resistance and improve clinical outcomes. We have developed a novel class of silicon-containing compounds and evaluated the anticancer activities and mechanism of action using cellular and animal models of drug-resistant PCa. Five organosilicon compounds were evaluated for their anticancer activities in the NCI-60 panel and established drug-resistant PCa cell lines. GH1504 exhibited potent in vitro cytotoxicity in a broad spectrum of human cancer cells, including PCa cells refractory to ADT and chemotherapy. Molecular studies identified several potential targets of GH1504, most notably androgen receptor (AR), AR variant 7 (AR-v7) and survivin. Mechanistically, GH1504 may promote the protein turnover of AR, AR-v7 and survivin, thereby inducing apoptosis in ADT-resistant and chemoresistant PCa cells. Animal studies demonstrated that GH1504 effectively inhibited the in vivo growth of ADT-resistant CWR22Rv1 and chemoresistant C4-2B-TaxR xenografts in subcutaneous and intraosseous models. These preclinical results indicated that GH1504 is a promising lead that can be further developed as a novel therapy for drug-resistant PCa., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2021. Published by Elsevier Inc.)

The Threshold of Toxicological Concern (TTC) for non-genotoxic substances, a risk assessment tool to establish safe exposure levels for chemicals with insufficient toxicological data, is based on the 5th percentile of cumulated distributions of Point of Departures in a high amount of repeat-dose, developmental and reproductive toxicity studies, grouped by Cramer Classes. The lack of organosilicon compounds in this dataset has resulted in regulatory concerns over the applicability of the TTC concept for this chemistry. We collected publicly available, scientifically robust oral repeat-dose and DART studies for 71 organosilicon substances for inclusion in the existing TTC dataset, using criteria for evaluation of studies and derivation of points of departure analogous to the Munro and COSMOS TTC publications. The resulting 5th percentile of this dataset was 13-fold higher than the 5th percentile for Cramer Class III compounds reported by Munro (which is the default for silicon-containing substances). Both the existing TTC for Cramer Class III compounds from Munro (1.5 μg/kg bw/day) and the COSMOS TTC (2.3 μg/kg bw/day), recommended by the SCCS for cosmetics-related substances, provide a conservative and sufficiently protective approach for this class of chemistry., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Luminescent cyclometallated iridium(III) complexes with a polyhedral oligomeric silsesquioxane (POSS) unit were designed as efficient theranostic agents that displayed tuneable organelle-targeting properties, minimal dark cytotoxicity and substantial photocytotoxicity even under hypoxic conditions.

Hypoxia, induced by inadequate oxygen supply, is a key indication of various major illnesses, which necessitates the need to develop new nanoprobes capable of sensing hypoxia environments for the targeted system monitoring and drug delivery. Herein, we report a hypoxia-responsive, periodic mesoporous organosilica (PMO) nanocarrier for repairing hypoxia damage. β-cyclodextrin (β-CD) capped azobenzene functionalization on the PMO surface could be effectively cleaved by azoreductase under a hypoxia environment. Moreover, the nanosystem is equipped with fluorescence resonance energy transfer (FRET) pair (tetrastyrene derivative (TPE) covalently attached to the PMO framework as the donor and Rhodamine B (RhB) in the mesopores as the receptor) for intracellular visualization and tracking of drug release in real-time. The design of intelligent nanocarriers capable of simultaneous reporting and treating of hypoxia conditions highlights a great potential in the biomedical domain.

Chronic pain and depression often coexist sharing common pathological mechanisms, and available analgesics and antidepressants have demonstrated limited clinical efficacy. Evidence has demonstrated that neuronal oxidative stress, apoptosis, and also glucocorticoid receptor dysregulation facilitate the occurrence and development of both chronic pain and depression. This study evaluated the effect of the organoselenium compound m-trifluoromethyl-diphenyl diselenide [(m-CF 3 -PhSe) 2 ] in the pain-depression comorbidity induced by reserpine. Mice were treated with reserpine 0.5 mg/kg for 3 days (intraperitoneal, once a day), and in the next 2 days, they were treated with (m-CF 3 -PhSe) 2 10 mg/kg (intragastric, once a day). Thirty minutes after the last administration of (m-CF 3 -PhSe) 2 , mice were subjected to the behavioral testing. (m-CF 3 -PhSe) 2 treatment reverted the reserpine-increased thermal hyperalgesia and depressive-like behavior observed in the hot-plate test and forced swimming test, respectively. Reserpine provoked a decrease of crossings and rearings in the open-field test, while (m-CF 3 -PhSe) 2 presented a tendency to normalize these parameters. Reserpine and/or (m-CF 3 -PhSe) 2 treatments did not alter the locomotor activity of mice observed in the rota-rod test. These effects could be related to modulation of oxidative stress, apoptotic pathway, and glucocorticoid receptors, once (m-CF 3 -PhSe) 2 normalized thiobarbituric acid reactive substances and 4-hydroxynonenal modified protein levels, markers of lipoperoxidation, poly(ADP-ribose) polymerase cleaved/total ratio, and glucocorticoid receptor levels increased by reserpine in the hippocampus. Considering that pain-depression dyad is a complex state of difficult treatment, this organoselenium compound could raise as an interesting alternative to treat pain-depression condition., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background/aims: IR700DX-6T and IR700DX-mbc94 are two chemically synthesized photosensitizers (PSs) that target the translocator protein (TSPO) and type 2 cannabinoid receptor (CB 2 R), respectively, for photodynamic therapy (PDT) of cancer. Recently, we found that IR700DX-6T and IR700DX-mbc94 exhibited high selectivity and efficiency in PDT for breast cancer and malignant astrocytoma. Yet, the phototherapeutic effects of the PSs on pancreatic cancer and underlying mechanisms remain unknown. This study investigated the effect of IR700DX-6T- or IR700DX-mbc94-PDT on pancreatic cancer and whether the treatment involves eliciting anticancer immune responses in support of superior therapeutic efficacy., Methods: Four pancreatic cancer cell lines were used for in vitro studies. C57BL/6 mice bearing pancreatic cancer cell-derived xenografts were generated for in vivo studies regarding the therapeutic effects of IR700DX-6T-PDT and IR700DX-mbc94-PDT on pancreatic cancer. The immunostimulatory or immunosuppressive effects of IR700DX-6T-PDT and IR700DX-mbc94-PDT were examined by detecting CD8 + T cells, regulatory T cells (T regs ), and dendritic cells (DCs) using flow cytometry and immunohistochemistry (IHC)., Results: TSPO and CB 2 R were markedly upregulated in pancreatic cancer cells and tissues. Both IR700DX-6T-PDT and IR700DX-mbc94-PDT significantly inhibited pancreatic cancer cell growth in a dose- and time-dependent manner. Notably, assessment of anticancer immune responses revealed that both IR700DX-6T-PDT and IR700DX-mbc94-PDT significantly induced CD8 + T cells, promoted maturation of DCs, and suppressed T regs , with stronger effects exerted by IR700DX-6T-PDT compared to IR700DX-mbc94-PDT., Conclusions: IR700DX-6T-PDT and IR700DX-mbc94-PDT involves eliciting anticancer immune responses. Our study has also implicated that PDT in combination with immunotherapy holds promise to improve therapeutic efficacy for patients with pancreatic cancer., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Human immunodeficiency virus (HIV-1) is still a major problem, not only in developing countries but is also re-emerging in several developed countries, thus the development of new compounds able to inhibit the virus, either for prophylaxis or treatment, is still needed. Nanotechnology has provided the science community with several new tools for biomedical applications. G2-S16 is a polyanionic carbosilane dendrimer capable of inhibiting HIV-1 in vitro and in vivo by interacting directly with viral particles. One of the main barriers for HIV-1 eradication is the reservoirs created in primoinfection. These reservoirs, mainly in T cells, are untargetable by actual drugs or immune system. Thus, one approach is inhibiting HIV-1 from reaching these reservoir cells. In this context, macrophages play a main role as they can deliver viral particles to T cells establishing reservoirs. We showed that G2-S16 dendrimer is capable of inhibiting the infection from infected macrophages to healthy T CD4/CD8 lymphocytes by eliminating HIV-1 infectivity inside macrophages, so they are not able to carry infectious particles to other body locations, thus preventing the reservoirs from forming.

Studies reveal that oxidative stress is associated with adverse effects of long-term morphine treatment. The m -trifluoromethyl-diphenyl diselenide (CF3) is a multi-target organoselenium compound that has antioxidant properties in different experimental models. This study aimed to investigate the CF3 effects against redox imbalance in peripheral and central tissues of mice, after single or multiple morphine doses. Swiss male mice received a single dose of morphine (5 mg/kg, s.c.) and CF3 (10 mg/kg, i.g.), or morphine was repeatedly injected (5 mg/kg, s.c.) and CF3 (10 mg/kg, i.g.) administered twice daily for 7 days. Oxidative stress was determined in the hippocampus, liver, and kidney. CF3 reversed the increase in reactive species caused by single and multiple morphine doses in the peripheral tissues. CF3 increased hepatic non-protein thiol levels and the superoxide dismutase (SOD) activity decreased by a single morphine dose. CF3 reversed the reduction in SOD activity in the kidney of mice repeatedly exposed to morphine. The study demonstrates that peripheral tissues were more susceptible than the hippocampus to oxidative stress induced by morphine in mice. The results show that CF3 modulated parameters of oxidative stress modified by single and multiple morphine administrations in peripheral and central tissues of mice.

Near-infrared photoimmunotherapy (NIR-PIT) is a cell selective cancer therapy that uses an antibody-photoabsorber (IRDye700DX, IR700) conjugate (APC) and NIR light. NIR-PIT targeting epidermal growth factor receptor (EGFR) in head and neck cancer (HNC) was conditionally approved in Japan in 2020. APC-bound tumors can be detected using endoscopic fluorescence imaging, whereas NIR light can be delivered using endoscopic fiber optics. The aims of this study were: (1) to assess the feasibility of endoscopic NIR-PIT in an orthotopic HNC model using a CD44-expressing MOC2-luc cell line; and (2) to evaluate quantitative fluorescence endoscopic imaging prior to and during NIR-PIT. The results were compared in 3 experimental groups: (1) untreated controls, (2) APC injection without light exposure (APC-IV), and (3) APC injection followed by NIR light exposure (NIR-PIT). APC injected groups showed significantly higher fluorescence signals for IR700 compared with the control group prior to therapeutic NIR light exposure, and the fluorescence signal significantly decreased in the NIR-PIT group after light exposure. After treatment, the NIR-PIT group showed significantly attenuated bioluminescence compared with the control and the APC-IV groups. Histology demonstrated diffuse necrotic death of the cancer cells in the NIR-PIT group alone. In conclusion, endoscopically delivered light combined with quantitative fluorescence imaging can be used to "see and treat" HNC. This method could also be applied to other types of cancer approachable with endoscopy., (Published 2021. This article is a U.S. Government work and is in the public domain in the USA. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

The immunological synapse is a complex structure that decodes stimulatory signals into adapted lymphocyte responses. It is a unique window to monitor lymphocyte activity because of development of systematic quantitative approaches. Here we demonstrate the applicability of high-content imaging to human T and natural killer (NK) cells and develop a pipeline for unbiased analysis of high-definition morphological profiles. Our approach reveals how distinct facets of actin cytoskeleton remodeling shape immunological synapse architecture and affect lytic granule positioning. Morphological profiling of CD8 + T cells from immunodeficient individuals allows discrimination of the roles of the ARP2/3 subunit ARPC1B and the ARP2/3 activator Wiskott-Aldrich syndrome protein (WASP) in immunological synapse assembly. Single-cell analysis further identifies uncoupling of lytic granules and F-actin radial distribution in ARPC1B-deficient lymphocytes. Our study provides a foundation for development of morphological profiling as a scalable approach to monitor primary lymphocyte responsiveness and to identify complex aspects of lymphocyte micro-architecture., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

The selective inhibition of immunoproteasome is a valuable strategy to treat autoimmune, inflammatory diseases, and hematologic malignancies. Recently, a new series of amide derivatives as non-covalent inhibitors of the β1i subunit with K i values in the low/submicromolar ranges have been identified. Here, we investigated the binding mechanism of the most potent and selective inhibitor, N -benzyl-2-(2-oxopyridin-1(2H)-yl)propanamide ( 1 ), to elucidate the steps from the ligand entrance into the binding pocket to the ligand-induced conformational changes. We carried out a total of 400 ns of MD-binding analyses, followed by 200 ns of plain MD. The trajectories clustering allowed identifying three representative poses evidencing new key interactions with Phe31 and Lys33 together in a flipped orientation of a representative pose. Further, Binding Pose MetaDynamics (BPMD) studies were performed to evaluate the binding stability, comparing 1 with four other inhibitors of the β1i subunit: N -benzyl-2-(2-oxopyridin-1(2H)-yl)acetamide ( 2 ), N -cyclohexyl-3-(2-oxopyridin-1(2H)-yl)propenamide ( 3 ), N -butyl-3-(2-oxopyridin-1(2H)-yl)propanamide ( 4 ), and ( S )-2-(2-oxopyridin-1(2H)-yl)- N ,4-diphenylbutanamide ( 5 ). The obtained results in terms of free binding energy were consistent with the experimental values of inhibition, confirming 1 as a lead compound of this series. The adopted methods provided a full dynamic description of the binding events, and the information obtained could be exploited for the rational design of new and more active inhibitors.

Human induced pluripotent stem cells (hiPSCs) are important starting materials for cell therapy products (CTPs) used for transplantation. During cell culture, hiPSCs often spontaneously undergo morphological changes and lose pluripotency. Such cells are called 'deviated cells', which are deviated from the undifferentiated state of hiPSCs, lack the expression of hiPSC markers and become positive for the early differentiation marker SSEA1 (stage-specific embryonic antigen 1, Lewis X glycan). Previously, we identified fibronectin (FN) as a predominant carrier protein of SSEA1 secreted from deviated cells, but not hiPSCs. A sandwich assay using antibodies (Abs) against FN and SSEA1 was developed for non-destructive quantitative evaluation of deviated cells present in hiPSC cultures. In this study, a novel technology was developed to specifically eliminate deviated cells using an anti-FN Ab along with a near-infrared (NIR) photoabsorber, IRDye700DX N-hydroxysuccinimide ester (IR700), which has been used for cancer photoimmunotherapy. The anti-FN Ab conjugated with the IR700 dye (IR700-αFN) bound to and induced the death of deviated cells upon NIR irradiation. In contrast, IR700-αFN failed to stain the hiPSCs, and IR700-αFN/NIR had little or no effect on survival. Finally, IR700-αFN/NIR irradiation induced selective removal of deviated cells from a mixed culture with hiPSCs, demonstrating that the proposed method is suitable for the removal of unwanted deviated cells present in hiPSC culture for the production of CTPs., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Prodrugs that allow in situ chemical conversion of less toxic precursors into active drugs in response to certain stimuli are promising anticancer candidates. Herein, we present a novel design of nanoprodrugs with a "degradation-mediated self-toxification" strategy, which realizes intracellular synthesis of anticancer agents using the nanoparticles' own degradation fragments as the precursors. To fulfill this concept, a metal complexing dicyclohexylphosphine (DCP) organosilane is carefully screened out from various ligands to conjugate onto Pd(OH) 2 nanodots confined hollow silica nanospheres (PD-HSN). This constructed nanoprodrug shows acid-triggered degradation in lysosomes and neutralizes protons to induce lysosomes rupturing, generating predesigned less toxic fragments (Pd 2+ and DCP-silicates) that complex into DCP/Pd complex in situ for inducing DNA damage, leading to enhanced anticancer activity against various cancer cell lines as well as in a xenograft tumour model., (© 2021 Wiley-VCH GmbH.)

Energy-dense foods and ethanol consumption are associated with mood disorders. m-Trifluoromethyl-diphenyl diselenide [(m-CF 3 -PhSe) 2 ] has been a prominent pharmacological target due to its antidepressant-like effects. This study investigated if the modulation of opioid and glucocorticoid receptors and its well-known antioxidant property contribute to the (m-CF 3 -PhSe) 2 antidepressant-like effect in young mice subjected to an energy-dense diet and ethanol intake. Swiss male mice [postnatal day (PND) 25] were exposed to an energy-dense diet (containing 20% fat and 20% carbohydrate) or standard chow until the PND 67. Mice received ethanol (2 g/kg) or water administration (3 times a week, intragastrically [i.g.]) from PND 45 to PND 60. After that, mice received (m-CF 3 -PhSe) 2 (5 mg/kg/day; i.g) or vegetal oil administration from PND 60 to 66. Mice performed the behavioral tests to evaluate the depressive-like phenotype. The results showed that individually neither an energy-dense diet nor ethanol group induced a depressive-like phenotype, but the association of both induced this phenotype in young mice. Oxidative stress was characterized by the increase of malondialdehyde, the decrease in the superoxide dismutase activity, and non-protein sulfhydryl levels in the cerebral cortex of depressive-like mice. Depressive-like mice showed an increase in the protein levels of opioid receptors and depletion in those of glucocorticoid. (m-CF 3 -PhSe) 2 abolished depressive-like phenotype and oxidative stress as well as modulated the levels of glucocorticoid and opioid receptors. In conclusion, the modulation of opioid and glucocorticoid receptors and the antioxidant property contributed to the (m-CF 3 -PhSe) 2 antidepressant-like effect in young mice exposed to an energy-dense diet and ethanol intake.

A new silicon phthalocyanine with piperazine-furan ring and its quaternized form were synthesized. All compounds were analyzed by spectroscopic techniques (FT-IR, 1 H-NMR, MS, and UV-vis), and the absorbance characteristics of silicon phthalocyanines were evaluated with the expected strong typical absorption bands in the far-red spectrum. The cytotoxic effects of these phthalocyanines induced by photodynamic therapy (PDT) were determined in a dose-dependent manner. Following cytotoxicity analysis, flow cytometric research of cell death was performed. The formation of reactive oxygen species (ROS) was determined by confocal microscopy. High levels of cytotoxicity and decreased viable cell population have been detected in cancer cells after treatment. In addition, ROS formation was observed in PDT treated cancer cells. However, low levels of cell death and ROS formation were observed in non-tumorigenic cells. According to western blot data, PDT-mediated treatment was found to provide different expression patterns of the cleaved PARP1 protein. The presented study demonstrates that PDT-mediated treatment of newly synthesized phthalocyanines has significant anti-cancer effects on breast cancer cells and may induce different cell death pathways., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In this study, compounds 1 and 2, and their silicon(iv) phthalocyanine (SiPc) derivatives 3 and 4, which bear these ligands as substituents on the axial positions were synthesized. These SiPcs (3 and 4) were also converted to their water soluble derivatives (3a and 4a). All these novel compounds were fully characterized by a combination of spectroscopic data such as FT-IR, 1 H-NMR, 13 C-NMR and UV-vis as well as mass spectroscopy. The photophysicochemical properties (fluorescence quantum yields and lifetimes, singlet oxygen, and photodegradation quantum yields) were investigated in DMSO for all the studied SiPcs (3 and 4) and in both DMSO and aqueous solutions for the water soluble SiPcs (3a and 4a). Effects of quaternization of these phthalocyanines on photophysicochemical properties were also determined. The photodynamic therapy activities of the water soluble SiPcs (3a and 4a) were tested against to the HeLa cancer cell lines and these phthalocyanines exhibited cytotoxicity against these cell lines.

Photodynamic therapy (PDT) is an anti-tumor modality which employs three individually non-toxic substances, including photosensitizer, light and oxygen, to produce a toxic effect. Besides causing damage to blood vessels that supply oxygen and nutrients to the tumor and killing the tumor by a direct cytotoxic effect, PDT has also been known to trigger an anti-tumor immune response. For instance, our previous study showed that PDT with BAM-SiPc, a silicon(IV) phthalocyanine based-photosensitizer, can not only eradicate the mouse CT26 tumor cells in a Balb/c mouse model, but also protect the mice against further re-challenge of the tumor cells through an immunomodulatory mechanism. To understand more about the immune effect, the biochemical actions of BAM-SiPc-PDT on CT26 cells were studied in the in vitro system. It was confirmed that the PDT treatment could induce immunogenic necroptosis in the tumor cells. Upon treatment, different damage-associated molecular patterns were exposed onto the cell surface or released from the cells. Among them, calreticulin was found to translocate to the cell membrane through a pathway similar to that in chemotherapy. The activation of immune response was also demonstrated by an increase in the expression of different chemokines.

Cancer has become an important public problem in worldwide since cancer incidence and mortality are growing rapidly. In this study, water soluble and non-aggregated silicon (IV) phthalocyanines and naphthalocyanines containing (3,5-bis{3-[3-(diethylamino)phenoxy]propoxy}phenyl)methoxy groups have been synthesized and characterized to investigate their anticancer potential. Their DNA binding/nuclease, topoisomerases inhibition were investigated using UV-Vis absorption, thermal denaturation and agarose gel electrophoresis. The in vitro cytotoxic properties of the compounds on human lung (A549), breast (BT-20), liver (SNU-398), prostate (DU-145), melanoma (SK-Mel 128) carcinoma and human fibroblast (HFC) normal cell lines were evaluated by using MTT assay. In order to determine the mechanism of cancer cell growth suppression, cell cycle analysis was carried out using flow cytometer on A549 cell line. The K b values of SiPc1a and SiNc2a were 6.85 ± (0.35) × 10 6 and 1.72 ± (0.16) × 10 4 M -1 and T m values of ct-DNA were calculated as 82.02 °C and 78.07 °C, respectively in the presence of both compounds. The Δ Tm values of SiPc1a and SiNc2a were calculated as 6.45 and 2.50 °C, respectively. The nuclease effects of SiPc1a and SiNc2a with supercoiled plasmid pBR322 DNA demonstrated that both compounds did not trigger any DNA nuclease effects at the lowest concentrations without irradiation whereas both compounds in the presence of activating agent (H 2 O 2 ) showed significant plasmid DNA nuclease actions under irradiation (22.5 J/cm 2 ). SiPc1a and SiNc2a inhibited to topoisomerase I on increasing concentrations whilst they had lower inhibition action toward topoisomerase II that of topoisomerase I. The in vitro cytotoxicity studies displayed that SiPc1a had the highest cytotoxic effects among the tested compounds against A549, SNU-398, SK-MEL128, DU-145, BT-20 and HFC cell lines with CC 50 values ranged from 0.49 to 2.99 µM. Furthermore, SiPc1a inhibited cell proliferation by cell cycle arrest in G 0 /G 1 phase. All of these results suggested that SiPc1a is a promising candidate as an anticancer agent., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Hospital acquired infections (HAI) are the most common complication found in the hospital environment. The aim of the study was to examine whether the use of an antimicrobial coating in high-touch areas in an orthopedic ward could reduce bacterial growth and HAI., Methods: From December 2017 to February 2018, HAI were registered on two orthopedic wards. A second registration was performed from December 2018 to February 2019. On the second occasion, an antimicrobial organosilane coating was applied just before the study period and thereafter weekly on one ward, while the other ward served as a control. Twenty defined high-touch areas on each ward were cultured before treatment and after 1, 2, 4, 8, 12, 14 and 16 weeks. Samples were cultured for aerobic colony counts, Staphylococcus aureus and E. coli., Results: The total aerobic colony counts were 47% lower on the treated ward compared with the non-treated ward over the study period (p = 0.02). The colony counts for Staphylococcus aureus and E. coli were low on both wards. During the first registration period, the incidence of HAI was 22.7% and 20.0% on the non-treated and subsequently treated ward respectively. On the second occasion, after treatment, the incidence was 25.0% and 12.5% (treated ward) respectively (p = 0.0001)., Conclusions: The use of a long-lasting antimicrobial organosilane coating appears to reduce the bioburden and reduce HAI. Since the incidence of HAI varies substantially over time, longer observation times are needed.

The current trend of cancer therapy has changed from monotherapy to synergistic or combination therapies. Among the treatment strategies, photodynamic therapy (PDT) and starvation therapy are widely employed together. However, the therapeutic effect of these treatments could lead to strong resistance and poor prognosis due to tumor hypoxia. Therefore, a smart nanoplatform (MONs-GOx@MnO2-Ce6) has been constructed herein by the assembly of glucose oxidase (GOx)-coated mesoporous organosilica nanoparticles (MONs) and MnO2 nanosheets-chlorin e6 (Ce6), which form a nanosystem. Once MONs-GOx@MnO2-Ce6 enter tumor cells, it catalyzes the oxidation of glucose using oxygen (O2) and generates hydrogen peroxide (H2O2) and gluconic acid, the former of which may accelerate the decomposition of MnO2 nanosheets. The released MnO2 nanosheets would regenerate O2 in the presence of H2O2. In this case, MnO2 nanosheets serve as (i) a nanocarrier and fluorescence quencher for the photosensitizer Ce6, (ii) a degradable material that is activated by the tumor microenvironment (TME) for fluorescence recovery, and (iii) an O2-producing carrier that reacts with H2O2 for relieving hypoxia in the tumor, which contributes to the combined starvation/photodynamic cancer therapy since these treatment strategies need O2. MONs-GOx@MnO2-Ce6 could not only realize cancer cell imaging, but also reduce intracellular glucose uptake and Glut1 expression, inhibiting the metabolism of cancer cells. This strategy shows great potential for clinical applications.

Body-on-a-chip and organ-on-a-chip systems utilize polydimethylsiloxane (PDMS) because of the relative suitability of the material for fabrication of microfluidic channels and chambers used in these devices. However, hydrophobic molecules, especially therapeutic compounds, tend to adsorb to PDMS, which may distort the dose-response curves that feed into the pharmacokinetic/pharmacodynamic models used to translate preclinical data into predictions of clinical outcomes. Surface modification by organosilanes is one method being explored to modify PDMS, but the effect of organosilanes on drug adsorption isotherms is not well characterized. We utilized Inverse Liquid-Solid Chromatography to characterize the adsorption parameters of the drugs acetaminophen, diclofenac, and verapamil with native PDMS and organosilane-modified (fluoropolymer (13F) and polyethylene glycol) PDMS surfaces, to correlate the modifications with changes in drug adsorption. It was determined that the organosilane modifications significantly changed the energy of adsorption of the test drug utilizing our methodology., (© 2020 American Institute of Chemical Engineers.)

Polyhedral oligomeric silsesquioxane (POSS) is a promising scaffold to be used as delivery system. POSS can modify the properties of photosensitizers to enhance their efficacy toward photodynamic therapy (PDT). In this work, we designed, synthesized and characterized five different POSS porphyrin ( POSSPs 1-5 ) derivatives containing hydrophobic ( 1 - 3 ) and hydrophilic ( 4 and 5 ) functional groups. In general, all the POSSPs showed a better singlet oxygen quantum yield than the parent porphyrins due to the steric hindrance from the POSS unique structure. POSSPs 1 and 3 containing isobutyl groups showed better PDT performance in cancer cells at lower concentrations than POSSPs 4 and 5 . However; at higher concentrations, the POSSP 4 containing hydrophilic groups has an enhanced PDT efficiency as compared with the parent porphyrin. We envision that the chemical tunability of POSSs can be used as a promising option to improve the delivery and performance of photosensitizers.

Background: CuS-modified hollow mesoporous organosilica nanoparticles (HMON@CuS) have been preferred as non-invasive treatment for cancer, as near infrared (NIR)-induced photo-thermal effect (PTT) and/or photo-dynamic effect (PDT) could increase cancer cells' apoptosis. However, the certain role of HMON@CuS-produced-PTT&PDT inducing gastric cancer (GC) cells' mitochondrial damage, remained unclear. Moreover, theranostic efficiency of HMON@CuS might be well improved by applying multi-modal imaging, which could offer an optimal therapeutic region and time window. Herein, new nanotheranostics agents were reported by Gd doped HMON decorated by CuS nanocrystals (called HMON@CuS/Gd)., Results: HMON@CuS/Gd exhibited appropriate size distribution, good biocompatibility, L-Glutathione (GSH) responsive degradable properties, high photo-thermal conversion efficiency (82.4%) and a simultaneous reactive oxygen species (ROS) generation effect. Meanwhile, HMON@CuS/Gd could efficiently enter GC cells, induce combined mild PTT (43-45 °C) and PDT under mild NIR power density (0.8 W/cm 2 ). Surprisingly, it was found that PTT might not be the only factor of cell apoptosis, as ROS induced by PDT also seemed playing an essential role. The NIR-induced ROS could attack mitochondrial transmembrane potentials (MTPs), then promote mitochondrial reactive oxygen species (mitoROS) production. Meanwhile, mitochondrial damage dramatically changed the expression of anti-apoptotic protein (Bcl-2) and pro-apoptotic protein (Bax). Since that, mitochondrial permeability transition pore (mPTP) was opened, followed by inducing more cytochrome c (Cyto C) releasing from mitochondria into cytosol, and finally activated caspase-9/caspase-3-depended cell apoptosis pathway. Our in vivo data also showed that HMON@CuS/Gd exhibited good fluorescence (FL) imaging (wrapping fluorescent agent), enhanced T1 imaging under magnetic resonance imaging (MRI) and infrared thermal (IRT) imaging capacities. Guided by FL/MRI/IRT trimodal imaging, HMON@CuS/Gd could selectively cause mild photo-therapy at cancer region, efficiently inhibit the growth of GC cells without evident systemic toxicity in vivo., Conclusion: HMON@CuS/Gd could serve as a promising multifunctional nanotheranostic platform and as a cancer photo-therapy agent through inducing mitochondrial dysfunction on GC.

The choice of nanocarriers is crucial to fabricate ideal therapeutic nanoplatform in the treatment of cancer. Considering the advantages brought by the two-dimensional (2D) materials with atomic thickness in drug loading and cellular uptake, herein, novel 2D biodegradable mesoporous organosilica nanosheets (MONSs) are presented, and their application in chemotherapy/mild thermotherapy of cancer is studied by loading chemotherapy drug doxorubicin (DOX) and conjugating ultrasmall CuS nanoparticles. It is found that the loading of DOX in MONSs is as high as 859 μg/mg due to their large surface area and intermediate void structure. The release of DOX from MONSs is intelligently controlled by pH value, glutathione (GSH) concentration, and laser irradiation. Excitingly, in comparison with traditional spherical mesoporous organosilica nanoparticles, as-prepared MONSs not only show more rapid degradation but also exhibit faster internalization and higher cellular uptake efficiency due to their larger aspect ratios and unique cellular internalization approach of 2D materials. A mild thermotherapy induced by ultrasmall CuS nanoparticles can further promote the cellular uptake and improve chemotherapy efficacy. The in vitro and in vivo experimental results reveal that the theranostic nanoplatform based on degradable MONSs has excellent biocompatibility and anticancer effects. Therefore, MONSs are expected to be a competitive alternative to existing silica-based nanomaterials in antitumor treatment.

Porphyrin-based periodic mesoporous organosilica nanoparticles (PMO) synthesized from a large functional octatriethoxysilylated porphyrin precursor and allowing two-photon excitation photodynamic therapy (TPE-PDT) and NIR imaging were synthesized. These PMO were grafted with polyethylene glycol (PEG) moieties and an analogue of mannose 6-phosphate functionalized at the anomeric position (AMFA). AMFAs are known to efficiently target mannose 6-phosphate receptors (M6PRs) which are over-expressed in various cancers. Here, we demonstrated for the first time that M6PRs were over-expressed in rhabdomyosarcoma (RMS) cells and could be efficiently targeted with PMO-AMFA allowing TPE imaging and TPE-PDT of RMS cells. The comparison with healthy myoblasts demonstrated an absence of biological effects, suggesting a cancer cell specificity in the biomedical action observed.

Anionic carbosilane dendrimers such as G2-S16 are very effective in preventing HSV-2 infection both in vitro and in vivo. We present the main achievements obtained for the G2-S16 dendrimer in vivo, especially related to its efficacy against HSV-2 infection. Moreover, we discuss the mechanisms by which the G2-S16 dendrimer applied vaginally as a topical microbicide has been demonstrated to be safe and harmless for the vaginal microbiome balance, as both conditions present an essential step that has to be overcome during microbicide development. This review points to the marked protective effect of the G2-S16 dendrimer against sexually transmitted HSV-2 infection, supporting its role as a possible microbicide against HSV-2 infection., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Chlorin e6 (Ce6), with its high phototoxic potential, has wide applications in photodynamic therapy (PDT) for many human diseases. However, poor cancer cell localization of Ce6 has limited its direct application for PDT. Here, we developed cancer-targeting peptide p 18-4/chlorin e6 (Ce6)-conjugated polyhedral oligomeric silsesquioxane (PPC) nanoparticles for improving the targeting ability of Ce6 to breast cancer cells, thereby enhancing PDT efficacy. The synthesized PPC nanoparticles exhibited a spherical shape with an average diameter of 127.2 ± 11.3 nm in aqueous solution. Compared with free Ce6, the immobilization of p 18-4 enhanced the in vitro cellular uptake and targeting ability of PPC nanoparticles in breast cancer cell line MDA-MB-231. In addition, the intracellular uptake of PPC nanoparticles in MDA-MB-231 cells was dramatically increased compared with other cancer cells, indicating an obvious targeting ability of PPC nanoparticles on breast cancer cells. Upon light irradiation, PPC nanoparticles revealed significantly improved phototoxicity to MDA-MB-231 cells, mainly due to apoptotic cell death. In vivo PDT study suggested that PPC nanoparticles exhibited increased retention in tumor tissues and effectively inhibited the growth of MDA-MB-231 tumors in a target-specific manner. Overall, these results indicate that PPC nanoparticles are highly effective PDT agents for breast cancer therapy., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In this study, novel silicon(iv) phthalocyanines axially disubstituted with bis[(4-{3-[3-(dimethylamino)phenoxy]propoxy}phenyl)methoxy] and bis[(4-{3-[3-(diethylamino)phenoxy]propoxy}phenyl)methoxy] groups and their quaternized derivatives were synthesized and characterized. Then, their supercoiled pBR322 plasmid DNA cleavage properties were investigated using agarose gel electrophoresis. The in vitro PDT effects of Si-3a and Si-4a were investigated using the MTT cell viability assay against HCT-116, A549 and SH-SY5Y cell lines. Si-3a and Si-4a did not show cleavage effects upon increasing concentrations in the dark but both compounds showed cleavage activities upon irradiation for 30 and 60 min, respectively. The MTT cell viability assay indicated that Si-4a had a cytotoxic effect in a concentration-dependent manner on the HCT-116 cell line but it did not show any statistical difference with regard to phototoxicity. Otherwise, Si-3a and Si-4a had significant phototoxic effects when compared to cytotoxic effects against A549 and SH-SY5Y. The results suggested that Si-3a and Si-4a showed better cell death against SH-SY5Y than other cell lines with irradiation.

Organic phototheranostic nanomedicines with an optimized near-infrared (NIR) biological transparent window (700-900 nm) are highly desirable for the diagnosis and treatment of deep-seated tumors in clinic. As excellent organic photosensitizers for photodynamic therapy (PDT) with outstanding photo- and thermo-stability, phthalocyanines (Pcs) have been used as the building blocks of single-component nanomedicines. However, to the best of our knowledge, all the Pc-based single-component self-assemblies reported to date are of an H-aggregate nature. This results in the simultaneous self-quenching of fluorescence emission and photodynamic activity as well as greatly reduced tissue penetration due to blue-shifted absorption. In the present work, intramolecular hydrogen bonding was formed between the two long and flexible axial NH2-terminated diethylene glycol ligands of the amphiphilic SiPc molecule (SiPc-NH2) in solution, leading to the employment of a cis-conformation of this molecule according to the 1H-NMR spectroscopy result, which as a building block then further self-assembled into monodisperse nanospheres (SiPcNano) with a J-aggregation nature on the basis of electronic absorption spectroscopic results. As a result, SiPcNano exhibited significantly enhanced red-shifted absorption in the NIR range of 750-850 nm and fluorescence emission. This in combination with the increased photodynamic effect for SiPcNano triggered by the protonation of amine groups due to the acidic nature of tumors endowed effective synergistic NIR photodynamic and photothermal effects in different cancer cells and thus effective inhibition of tumor growth in A549 tumor-bearing mice on the basis of a series of in vitro and in vivo evaluations. The present result provides a new approach for constructing novel single-component NIR organic nanomedicines for multifunctional cancer therapy.

We report a novel and facile organosilane plasma polymerization method designed to improve the surface characteristics of poly(tetrafluoroethylene) (PTFE). We hypothesized that the polymerized silane coating would provide an adhesive surface for endothelial cell proliferation due to a large number of surface hydroxyl groups, while the large polymer networks on the surface of PTFE would hinder platelet attachment. The plasma polymerized PTFE surfaces were then systematically characterized via different analytical techniques such as FTIR, XPS, XRD, Contact angle, and SEM. The key finding of the characterization is the time-dependent deposition of an organosilane layer on the surface of PTFE. This layer was found to provide favorable surface properties to PTFE such as a very high surface oxygen content, high hydrophilicity and improved surface mechanics. Additionally, in vitro cellular studies were conducted to determine the bio-interface properties of the plasma-treated and untreated PTFE. The important results of these experiments were rapid endothelial cell growth and decreased platelet attachment on the plasma-treated PTFE compared to untreated PTFE. Thus, this new surface modification technique could potentially address the current challenges associated with PTFE for blood contact applications, specifically poor endothelial cell growth and risk of thrombosis.

Biodegradable periodic mesoporous organosilica (BPMO) nanoparticles have emerged as a promising type of nanocarrier for drug delivery, given the biodegradable feature is advantageous for clinical translation. In this paper, we report synthesis and characterization of daunorubicin (DNR) loaded BPMO. DNR was loaded onto rhodamine B-labeled BPMO that contain tetrasulfide bonds. Tumor spheroids and chicken egg tumor models were used to characterize the activity in biological settings. In the first experiment we examined the uptake of BPMO into tumor spheroids prepared from ovarian cancer cells. BPMO were efficiently taken up into tumor spheroids and inhibited their growth. In the chicken egg tumor model, intravenous injection of DNR-loaded BPMO led to the elimination of ovarian tumor. Lack of adverse effect on organs such as lung appears to be due to excellent tumor accumulation of BPMO. Thus, DNR-loaded BPMO represents a promising nanodrug compared with free DNR currently used in cancer therapy. OK., (© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)