Boosting Upconversion Efficiency in Optically Inert Shelled Structures with Electroactive Membrane through Electron Donation.

This study innovatively addresses challenges in enhancing upconversion efficiency in lanthanide-based nanoparticles (UCNPs) by exploiting Shewanella oneidensis MR-1, a microorganism capable of extracellular electron transfer. Electroactive membranes, rich in c-type cytochromes, are extracted from bacteria and integrated into membrane-integrated liposomes (MILs), encapsulating core-shelled UCNPs with an optically inactive shell, forming UCNP@MIL constructs. The electroactive membrane, tailored to donate electrons through the inert shell, independently boosts upconversion emission under near-infrared excitation (980 or 1550 nm), bypassing ligand-sensitized UCNPs. The optically inactive shell restricts energy migration, emphasizing electroactive membrane electron donation. Density functional theory calculations elucidate efficient electron transfer due to the electroactive membrane hemes' highest occupied molecular orbital being higher than the valence band maximum of the optically inactive shell, crucial for enhancing energy transfer to emitter ions. The introduction of a SiO2 insulator coating diminishes light enhancement, underscoring the importance of unimpeded electron transfer. Luminescence enhancement remains resilient to variations in emitter or sensitizing ions, highlighting the robustness of the electron transfer-induced phenomenon. However, altering the inert shell material diminishes enhancement, emphasizing the role of electron transfer. This methodology holds significant promise for diverse biological applications. UCNP@MIL offers an advantage in cellular uptake, which proves beneficial for cell imaging.

Catalytic Nanoparticles in Biomedical Applications: Exploiting Advanced Nanozymes for Therapeutics and Diagnostics.

Catalytic nanoparticles (CNPs) as heterogeneous catalyst reveals superior activity due to their physio-chemical features, such as high surface-to-volume ratio and unique optical, electric, and magnetic properties. The CNPs, based on their physio-chemical nature, can either increase the reactive oxygen species (ROS) level for tumor and antibacterial therapy or eliminate the ROS for cytoprotection, anti-inflammation, and anti-aging. In addition, the catalytic activity of nanozymes could specifically trigger a specific reaction accompanied by the optical feature change, presenting the feasibility of biosensor and bioimaging applications. Undoubtedly, CNPs play a pivotal role in pushing the evolution of technologies in medical and clinical fields, and advanced strategies and nanomaterials rely on the input of chemical experts to develop. Herein, we present a systematic and comprehensive review of the challenges and recent development of catalytic NPs for biomedical applications from the viewpoint of advanced nanomaterial with unique catalytic activity and additional functions. Furthermore, we critically discuss the biosafety issue of applying biodegradable and non-biodegradable nanozymes and future perspectives to guide a promising direction in developing span-new nanozymes and more intelligent strategies for overcoming the current clinical limitations. This article is protected by copyright. All rights reserved.

Photo-Responsive Ascorbic Acid-Modified Ag2S-ZnS Heteronanostructure Dropping pH to Trigger Synergistic Antibacterial and Bohr Effects for Accelerating Infected Wound Healing.

Nonantibiotic approaches must be developed to kill pathogenic bacteria and ensure that clinicians have a means to treat wounds that are infected by multidrug-resistant bacteria. This study prepared matchstick-like Ag2S-ZnS heteronanostructures (HNSs). Their hydrophobic surfactants were then replaced with hydrophilic poly(ethylene glycol) (PEG) and thioglycolic acid (TGA) through the ligand exchange method, and this was followed by ascorbic acid (AA) conjugation with TGA through esterification, yielding well-dispersed PEGylated Ag2S-ZnS@TGA-AA HNSs. The ZnS component of the HNSs has innate semiconductivity, enabling the generation of electron-hole pairs upon irradiation with a light of wavelength 320 nm. These separate charges can react with oxygen and water around the HNSs to produce reactive oxygen species. Moreover, some holes can oxidize the surface-grafted AA to produce protons, decreasing the local pH and resulting in the corrosion of Ag2S, which releases silver ions. In evaluation tests, the PEGylated Ag2S-ZnS@TGA-AA had synergistic antibacterial ability and inhibited Gram-negative Escherichia coli and Gram-positive methicillin-resistant Staphylococcus aureus (MRSA). Additionally, MRSA-infected wounds treated with a single dose of PEGylated Ag2S-ZnS@TGA-AA HNSs under light exposure healed significantly more quickly than those not treated, a result attributable to the HNSs' excellent antibacterial and Bohr effects.

Prussian blue analog with separated active sites to catalyze water driven enhanced catalytic treatments.

Chemodynamic therapy (CDT) uses the Fenton or Fenton-like reaction to yield toxic ‧OH following H2O2 → ‧OH for tumoral therapy. Unfortunately, H2O2 is often taken from the limited endogenous supply of H2O2 in cancer cells. A water oxidation CoFe Prussian blue (CFPB) nanoframes is presented to provide sustained, external energy-free self-supply of ‧OH from H2O to process CDT and/or photothermal therapy (PTT). Unexpectedly, the as-prepared CFPB nanocubes with no near-infrared (NIR) absorption is transformed into CFPB nanoframes with NIR absorption due to the increased Fe3+-N ≡ C-Fe2+ composition through the proposed proton-induced metal replacement reactions. Surprisingly, both the CFPB nanocubes and nanoframes provide for the self-supply of O2, H2O2, and ‧OH from H2O, with the nanoframe outperforming in the production of ‧OH. Simulation analysis indicates separated active sites in catalyzation of water oxidation, oxygen reduction, and Fenton-like reactions from CFPB. The liposome-covered CFPB nanoframes prepared for controllable water-driven CDT for male tumoral mice treatments.

Atomically dispersed golds on degradable zero-valent copper nanocubes augment oxygen driven Fenton-like reaction for effective orthotopic tumor therapy.

Herein, we employ a galvanic replacement approach to create atomically dispersed Au on degradable zero-valent Cu nanocubes for tumor treatments on female mice. Controlling the addition of precursor HAuCl4 allows for the fabrication of different atomic ratios of AuxCuy. X-ray absorption near edge spectra indicates that Au and Cu are the predominant oxidation states of zero valence. This suggests that the charges of Au and Cu remain unchanged after galvanic replacement. Specifically, Au0.02Cu0.98 composition reveals the enhanced •OH generation following O2 → H2O2 → •OH. The degradable Au0.02Cu0.98 released Cu+ and Cu2+ resulting in oxygen reduction and Fenton-like reactions. Simulation studies indicate that Au single atoms boot zero-valent copper to reveal the catalytic capability of Au0.02Cu0.98 for O2 → H2O2 → •OH as well. Instead of using endogenous H2O2, H2O2 can be sourced from the O2 in the air through the use of nanocubes. Notably, the Au0.02Cu0.98 structure is degradable and renal-clearable.

Polyaniline-Based Glyco-Condensation on Au Nanoparticles Enhances Immunotherapy in Lung Cancer.

Lung cancer is considered among the deadliest cancers with a poor prognosis. Au@PG nanoparticles (NPs) are gold (Au)-based NPs featuring a polyaniline-based glyco structure (PG) generated from the polymerization of ortho-nitrophenyl-ß-d-galactopyranoside (ONPG) with promising M1 macrophage polarization activity, resulting in tumor remodeling and from a cold to a hot microenvironment, which promotes the cytotoxic T cell response and tumor inhibition. The combination of Au@PG NPs and anti-programmed cell death protein 1 (PD-1) therapy improved tumor inhibition and immunosuppression, accompanied by the secretion of immunogenic cytokines. A one-pot synthetic method was developed to achieve glyco-condensation during the formation of Au@PG NPs, which induced macrophage polarization more efficiently than Au@glucose, Au@mannose, and Au@galactose NPs. The switch from M2 to M1 macrophages was dependent on NP size, with smaller Au@PG NPs performing better than larger ones, with effectiveness ranked as follows: 32.2 nm ≈ 29.8 nm < 26.4 nm < 18.3 nm. Cellular uptake by endocytosis induced size-dependent endoplasmic reticulum (ER) stress, which resulted in the activation of spleen tyrosine kinase (SYK), leading to immune modulations and macrophage polarization. Our results suggested the promising potential of Au@PG NPs in lung cancer immunotherapy.

Chemical Structure and Shape Enhance MR Imaging-Guided X-ray Therapy Following Marginative Delivery.

Ineffective site-specific delivery has seriously impeded the efficacy of nanoparticle-based drugs to a disease site. Here, we report the preparation of three different shapes (sphere, scroll, and oblate) to systematically evaluate the impact of the marginative delivery on the efficacy of magnetic resonance (MR) imaging-guided X-ray irradiation at a low dose of 1 Gy. In addition to the shape effect, the therapeutic efficacy is investigated for the first time to be strongly related to the structure effect that is associated with the chemical activity. The enhanced particle-vessel wall interaction of both the flat scroll and oblate following margination dynamics leads to greater accumulation in the lungs, resulting in superior performance over the sphere against lung tumor growth and suppression of lung metastasis. Furthermore, the impact of the structural discrepancy in nanoparticles on therapeutic efficacy is considered. The tetragonal oblate reveals that the feasibility of the charge-transfer process outperforms the orthorhombic scroll and cubic sphere to suppress tumors. Finally, surface area is also a crucial factor affecting the efficacy of X-ray treatments from the as-prepared particles.

Synchronization of Nanoparticle Sensitization and Radiosensitizing Chemotherapy through Cell Cycle Arrest Achieving Ultralow X-ray Dose Delivery to Pancreatic Tumors.

Pancreatic cancer is among the leading causes of cancer-related death and remains a formidable therapeutic challenge. To date, surgical resection and chemotherapy have been the standards of care. Methotrexate (MTX), which is recognized as a refractory drug for pancreatic cells, was conjugated to the surface of LiYF4:Ce3+ nanoparticles (NP-MTX) through a photocleavable linker molecule. When LiYF4:Ce3+ NPs are stimulated by X-rays, they emit light, which induces the photocleavage of the photolabile linker molecule to release MTX. MTX can target pancreatic tumors, which overexpress folic acid (FA) receptors and are internalized into the cell through receptor-mediated endocytosis. The synergistic effect of the NP-MTX treatment initiated by X-ray irradiation occurs due to the combination of nanoparticle sensitization and the radiosensitizing chemotherapy of the photocleaved MTX molecule. This dual sensitization effect mediated by NP-MTX enabled 40% dose enhancement, which corresponded with an increase in the generation of cytotoxic cellular reactive oxygen species (ROS) and enhanced S phase arrest within the cell cycle. The delivery of an ultralow radiation dose of 0.1 Gy resulted in the photocleavage of MTX from NP-MTX, and this strategy demonstrated in vivo efficacy against AsPC-1 and PANC-1 xenografted pancreatic tumors.

1550 nm excitation-responsive upconversion nanoparticles to establish dual-photodynamic therapy against pancreatic tumors.

The second near-infrared biological window b (NIR-IIb, 1500-1700 nm) is recently considered as the promising region for deeper tissue penetration. Herein, a nanocarrier for 1550 nm light-responsive dual-photodynamic therapy (PDT) is developed to efficiently boost singlet oxygen (1O2) generation. The dual-photosensitizers (PSs), rose bengal (RB) and chlorin e6 (Ce6), are carried by the silica-coated core-shell LiYbF4:Er@LiGdF4 upconversion nanoparticles (UCNPs), forming UCNP/RB,Ce6. Following 1550 nm laser irradiation, the upconversion emission of UCNP/RB,Ce6 in both green (∼550 nm) and red (∼670 nm) colors is fully utilized to activate RB and Ce6, respectively. The simultaneous triggering of dual-PS generates an abundant amount of 1O2 resulting in boosted PDT efficacy. This dual-PDT nanocarrier presents an enhanced anticancer effect under single dose treatment in comparison with the single-PS ones from in vitro and in vivo treatments. The marriage between the boosted dual-PDT and 1550 nm light excitation is anticipated to provide a new avenue for non-invasive therapy.

Aspect Ratio-Dependent Charge Carrier Dynamics in Matchstick-like Ag2S-ZnS Nanorods for Solar Hydrogen Generation.

Matchstick-like Ag2S-ZnS nanorods (NRs) with a tunable aspect ratio (AR) were synthesized using one-pot thermal decomposition. The ultraviolet photoelectron spectra and time-resolved photoluminescence spectra of the Ag2S-ZnS NRs were collected to study their electronic band structures and charge carrier dynamics. The energy difference (ΔE) at the interface between the ZnS stem and Ag2S tip was altered as the AR of Ag2S-ZnS NRs increased from 11.9 to 18.4, resulting in an enlarged driving force for the delocalized electrons along the conduction band of ZnS being injected into that of Ag2S. The interfacial electron transfer rate constant (ket) from ZnS to Ag2S could be enhanced by ∼2 orders of magnitude from 5.27 × 106 to 3.24 × 108 s-1, leading to a significant improvement in the efficiency of solar hydrogen generation. This investigation provides new physical insights into the manipulation of charge carrier dynamics by means of AR adjustment in semiconductor nanoheterostructures for photoelectric conversions.

Low Dose of X-Ray-Excited Long-Lasting Luminescent Concave Nanocubes in Highly Passive Targeting Deep-Seated Hepatic Tumors.

Chromium-doped zinc gallate, ZnGa2 O4 :Cr3+ (ZGC), is viewed as a long-lasting luminescence (LLL) phosphor that can avoid tissue autofluorescence interference for in vivo imaging detection. ZGC is a cubic spinel structure, a typical agglomerative or clustered morphology lacking a defined cubic shape, but a sphere-like feature is commonly obtained for the nanometric ZGC. The substantial challenge remains achieving a well-defined cubic feature in nanoscale. The process by which dispersed and well-defined concave cubic ZGC is obtained is described, exhibiting much stronger LLL in UV and X-ray excitation for the dispersed cubic ZGC compared with the agglomerative form that cannot be excited using X-rays with a low dose of 0.5 Gy. The cubic ZGC reveals a specific accumulation in liver and 0.5 Gy used at the end of X-ray excitation is sufficient for imaging of deep-seated hepatic tumors. The ZGC nanocubes show highly passive targeting of orthotopic hepatic tumors.

Enhancing Microcirculation on Multitriggering Manner Facilitates Angiogenesis and Collagen Deposition on Wound Healing by Photoreleased NO from Hemin-Derivatized Colloids.

A deficiency of nitric oxide (NO) supply has been found to impair wound healing. The exogenous topical delivery of NO is a promising approach to enhance vasodilation and stimulate angiogenesis and collagen deposition. In this study, the CN groups on the surface of Prussian blue (PB) nanocubes were carefully reduced to -CH2-NH2 to conjugate with COOH group of hemin consisting of a Fe-porphyrin structure with strong affinity toward NO. Accordingly, the NO gas was able to coordinate to hemin-modified PB nanocubes. The hemin-modified PB carrying NO (PB-NO) can be responsible to near-infrared (NIR) light (808 nm) exposure to induce the thermo-induced liberation of NO based on the light-to-heat transformation property of PB nanocubes. The NO supply on the incisional wound sites can be readily topically dropped the colloidal solution of PB-NO for receiving NIR light irradiation. The enhanced blood flow was in a controllable manner whenever the wound sites containing PB-NO received NIR light irradiation. The promotion of blood perfusion following the on-demand multidelivery of NO has effectively facilitated the process of wound closure to enhance angiogensis and collagen deposition.

Astragalus polysaccharide promotes the release of mature granulocytes through the L-selectin signaling pathway.

BACKGROUND: This study aims to investigate the leukogenic effect of astragalus polysaccharide (APS), to compare its effect of increasing the numbers of mature granulocytes with that of granulocyte colony-stimulating factor (G-CSF), and to investigate the mechanism. METHODS: Rats were arbitrarily grouped into four groups (control, cyclophosphamide (CTX), CTX + APS, and CTX + G-CSF groups), and each group was then arbitrarily divided into five subgroups according to the time period since CTX infusion (0, 4, 7, 10, and 14 days). The expression of leukocyte selectin (L-selectin), its ligand, and shedding-related protease on granulocytes was analyzed. Leukocyte counts were obtained. Chemotactic capacity of polymorphonuclear leukocytes (PMNLs) was assessed. RESULTS: Both APS and G-CSF restored the expression of L-selectin, P-selectin glycoprotein ligand-1 (PSGL-1), CD11b/CD18, and ADAM17 to normal levels (P > 0.05 vs. control group on each time point), with APS eliciting a greater effect than G-CSF (P = 0.005 on day 7, P < 0.001 on day 10 and 14 for L-selectin; P = 0.038 on day 7, P = 0.001 on day 10, P < 0.001 on day 14 for PSGL-1; P < 0.001 on day 7, 10 and 14 for ADAM17; P < 0.001 on day 7, 10, and 14 for CD11b/CD18). The percentages of the bands and segmented bone marrow (BM) cells in myeloid neutrophils were higher in the CTX + APS group than in the CTX group on day 7 (P = 0.030) and reached normal levels on day 10 (P = 0.547) and 14 (P = 0.431) vs. control group. The ability of APS to increase numbers of PMNLs in peripheral blood after chemotherapy was significantly superior to that of G-CSF 7 days after chemotherapy (P = 0.029 on day 10, P = 0.006 on day 14). Moreover, APS more significantly improved the chemotactic ability of PMNLs among mature BM granulocytes and peripheral blood neutrophils after chemotherapy than did G-CSF (P < 0.001 on day 7, P = 0.001 on day 10 and P = 0.005 on day 14). CONCLUSIONS: APS promoted the differentiation and chemotactic ability of BM granulocytes via the L-selectin signaling pathway.

Predictive value of circulating endothelial cells for efficacy of chemotherapy with Rh-endostatin in non-small cell lung cancer.

PURPOSE: The present study was designed to elucidate the fluctuation of activated CECs (aCECs) during different therapies and to investigate their predictive value for efficacy of anti-angiogenesis and chemotherapy in advanced non-small cell lung cancer (NSCLC). METHODS: Seventy-two patients were randomized into three arms, treated with concomitant NP (vinorelbine and cisplatin) and Rh-endostatin, Rh-endostatin followed by NP, and single NP up to a maximum of six cycles. Response, time to progression (TTP), and aCECs levels were observed. The correlation between aCECs and efficacy was analyzed. RESULTS: We found that TTP was 8.5 months in concomitant NP and Rh-endostatin versus 5.3 months in NP (p = 0.04) and 6.0 months in Rh-endostatin followed by NP. aCECs fluctuated during the therapeutic period, with a significantly high level from baseline on 8th day of Rh-endostatin followed by NP regimen, that is, when single Rh-endostatin was administered for 1 week, and upon completion of therapy in cases of progressive disease in each group (all p < 0.05). When TTP was longer than 10 months, aCECs count difference (∆aCECs, the difference in the aCECs by post-therapeutic amount minus pre-therapeutic amount) was reversely correlated to TTP (p = 0.003, r = -0.647). CONCLUSIONS: An improved synergistic effect was achieved from concomitant NP and Rh-endostatin compared with Rh-endostatin followed by NP and single NP. aCECs increased when the disease was aggravated or single Rh-endostatin treatment of Rh-endostatin was administered, while they decreased when a clinical response to the combined therapy was obtained. Our results suggest ∆aCECs as an ideal marker to predict the response to Rh-endostatin combined with chemotherapy.

Comparison of the effects of recombinant human endostatin and docetaxel on human umbilical vein endothelial cells in different growth states.

BACKGROUND: Recombinant human endostatin (rh-endostatin, Endostar) has been proved to be an inhibitor of angiogenesis. Docetaxel has been also considered as a common chemotherapeutic agent with inhibition of angiogenesis of malignancies. However, their function has been seldom compared and a best synergism protocol is not determined. This study aimed to compare the effects of two drugs, investigate their combined impact on human umbilical vein endothelial cells (HUVECs), a molecular basis and find ideal protocols to inhibit endothelial cell proliferation. METHODS: HUVECs on confluent growth or activated by vascular endothelial growth factor (VEGF) were treated by rh-endostatin or/and docetaxel at respective gradient concentration in following operations as cell proliferation determined by MTT assay, cell cycle distribution, apoptosis and markers of CD146, CD62E and CD105 detected by flow cytometery, the structure of the channel formed by HUVECs measured by tube formation count. RESULTS: Rh-endostatin exhibited time dependent inhibition of proliferation while docetaxel showed both time and dose dependent inhibition. HUVECs accumulated in G(0)-G(1) with decreased numbers of cells in G(2) after a single treatment of rh-endostatin or that followed by docetaxel treatment. Cells accumulated in G(2) after both a single docetaxel and simultaneous administration. Both the number of cells in G(0)-G(1) and apoptotic cells were increased by docetaxel followed by rh-endostatin treatment. The number of non-apoptotic cells at G(0)-G(1) was increased by first administering rh-endostatin then docetaxel. Sequential treatment of docetaxel followed by rh-endostatin resulted in the greatest increase in apoptosis (34.7%) and the second highest apoptosis was seen with simultaneous administration (18.2%). Expression of CD146 and CD105 on confluent HUVECs was reduced at certain doses of rh-endostatin and/or docetaxel. However, rh-endostatin reduced CD105 without any apparent impact on either CD146 or CD62E expression, whereas these markers were down-regulated by docetaxel after pre-activation by VEGF. Rh-endostatin treatment maintained tube-like structures for a limited time. In contrast, docetaxel swiftly reduced tube formation. Simultaneous treatment, or docetaxel followed by rh-endostatin, exhibited a stronger inhibition on tube formation than either agent alone. CONCLUSIONS: Both rh-endostatin and docetaxel can inhibit HUVEC proliferation while the high apoptotic rate after combined administration was probably owing to different sequent administration by docetaxel followed by rh-endostatin or simultaneous treatment. Both proliferation and adhesion molecules on HUVECs of confluent growth are down-regulated by the two drugs. The rh-endostatin decreased proliferation markers, but only slightly modified adhesion molecules, while both markers were down-regulated by docetaxel on HUVECs activated by VEGF. Rh-endostatin could maintain adhesion of HUVECs at first then induce cells apoptosis to damage tube formation. We hypothesize that it could lead to vascular normalization in short time. In contrast, docetaxel can suppress HUVEC proliferation, adhesion, and reduced tube formation swiftly due to its cytotoxicity. Combined treatments can induce a synergistic inhibition of tube formation.

[Analysis of cavitation of advanced NSCLC treated by rh-endostatin combined with NP chemotherapy].

OBJECTIVE: To study the significance of intra-tumoral cavitation in the patients with advanced NSCLC treated by rh-endostatin plus NP chemotherapy. METHODS: Fifty-seven patients with advanced NSCLC were randomly assigned to receive chemotherapy with rh-endostatin plus NP or NP alone. The numbers of activated circulating endothelial cells (aCECs) were measured by flow cytometry. Chest computed tomography was performed to evaluate the efficacy after 2 cycles of chemotherapy. RESULTS: Cavitation occurred in 5 of 29 patients in the rh-endostatin plus NP group, but not in any case of the NP group. Of the 5 patients, there were 2 males and 3 females, with pathological types of 3 adenocarcinomas, 1 adenosquamous cell carcinoma and 1 sarcomatoid carcinoma. All of these 5 cases had a peripherally located tumor in the CT scan. There was only one cavity in each case and most of these were roundish. Four cavities were situated in the center of the tumor and another one was eccentric. There were 3 cavities with thin wall and 2 with thick wall. Their average diameter was 2.7 cm. No hemoptysis occurred in these 5 patients. The blood-supply of the tumors showed by perfusion CT images was inhibited in 3 cases after treatment. The average number of aCECs decreased from 323.2/10(5) to 33.0/10(5) after treatment. CONCLUSION: Intratumoral cavitation is a peculiar imaging characteristics after anti-angiogenic therapy, which may be caused by inhibition of blood-supply to the tumor. CT perfusion imaging and measurement of activated circulating endothelial cells may be helpful to predict the efficacy of anti-angiogenic therapy combined with chemotherapy.