Defect-Engineered Tin Disulfide Nanocarriers as "Precision-Guided Projectile" for Intensive Synergistic Therapy.

Nanoformulations with endogenous/exogenous stimulus-responsive characteristics show great potential in tumor cell elimination with minimal adverse effects and high precision. Herein, an intelligent nanotheranostic platform (denoted as TPZ@Cu-SnS2-x /PLL) for tumor microenvironment (TME) and near-infrared light (NIR) activated tumor-specific therapy is constructed. Copper (Cu) doping and the resulting sulfur vacancies can not only improve the response range of visible light but also improve the separation efficiency of photogenerated carriers and increase the carrier density, resulting in the ideal photothermal and photodynamic performance. Density functional theory calculations revealed that the introduction of Cu and resulting sulfur vacancies can induce electron redistribution, achieving favorable photogenerated electrons. After entering cells through endocytosis, the TPZ@Cu-SnS2-x /PLL nanocomposites show the pH responsivity property for the release of the TPZ selectively within the acidic TME, and the released Cu2+ can first interact with local glutathione (GSH) to deplete GSH with the production of Cu+ . Subsequently, the Cu+ -mediated Fenton-like reaction can decompose local hydrogen peroxide into hydroxyl radicals, which can also be promoted by hyperthermia derived from the photothermal effect for tumor cell apoptosis. The integration of photoacoustic/computed tomography imaging-guided NIR phototherapy, TPZ-induced chemotherapy, and GSH-elimination/hyperthermia enhanced chemodynamic therapy results in synergistic therapeutic outcomes without obvious systemic toxicity in vivo.

Mitochondria-targeting Cu3VS4 nanostructure with high copper ionic mobility for photothermoelectric therapy.

Thermoelectric therapy has emerged as a promising treatment strategy for oncology, but it is still limited by the low thermoelectric catalytic efficiency at human body temperature and the inevitable tumor thermotolerance. We present a photothermoelectric therapy (PTET) strategy based on triphenylphosphine-functionalized Cu3VS4 nanoparticles (CVS NPs) with high copper ionic mobility at room temperature. Under near-infrared laser irradiation, CVS NPs not only generate hyperthermia to ablate tumor cells but also catalytically yield superoxide radicals and induce endogenous NADH oxidation through the Seebeck effect. Notably, CVS NPs can accumulate inside mitochondria and deplete NADH, reducing ATP synthesis by competitively inhibiting the function of complex I, thereby down-regulating the expression of heat shock proteins to relieve tumor thermotolerance. Both in vitro and in vivo results show notable tumor suppression efficacy, indicating that the concept of integrating PTET and mitochondrial metabolism modulation is highly feasible and offers a translational promise for realizing precise and efficient cancer treatment.

Theoretical simulation and experimental design of selenium and gold incorporated polymer-based microcarriers for ROS-mediated combined photothermal therapy.

Recently, multi-modal combined photothermal therapy (PTT) with the use of photo-active materials has attracted significant attention for cancer treatment. However, drug carriers enabling efficient heating at the tumor site are yet to be designed: this is a fundamental requirement for broad implementation of PTT in clinics. In this work, we design and develop hybrid carriers based on multilayer capsules integrated with selenium nanoparticles (Se NPs) and gold nanorods (Au NRs) to realize reactive oxygen species (ROS)-mediated combined PTT. We show theoretically and experimentally that cooperative interaction of Se NPs with Au NRs improves the heat release efficiency of the developed capsules. In addition, after uptake by tumor cells, intracellular ROS level amplified by Se NPs inhibits the tumor growth. As a consequence, the synergy between Se NPs and Au NRs exhibits the advantages of hybrid carriers such as (i) improved photothermal conversion efficiency and (ii) dual-therapeutic effect. The results of in vitro and in vivo experiments demonstrate that the combination of ROS-mediated therapy and PTT has a higher tumor inhibition efficiency compared to the single-agent treatment (using only Se-loaded or Au-loaded capsules). Furthermore, the developed hybrid carriers show negligible in vivo toxicity towards major organs such as the heart, lungs, liver, kidneys and spleen. This study not only provides a potential strategy for the design of multifunctional "all-in-one" carriers, but also contributes to the development of combined PTT in clinical practice.

"Electron Transport Chain Interference" Strategy of Amplified Mild-Photothermal Therapy and Defect-Engineered Multi-Enzymatic Activities for Synergistic Tumor-Personalized Suppression.

Arming activatable mild-photothermal therapy (PTT) with the property of relieving tumor thermotolerance holds great promise for overcoming traditional mild PTT limitations such as thermoresistance, insufficient therapeutic effect, and off-target heating. Herein, a mitochondria-targeting, defect-engineered AFCT nanozyme with enhanced multi-enzymatic activity was elaborately designed as a tumor microenvironment (TME)-activatable phototheranostic agent to achieve remarkable anti-tumor therapy via "electron transport chain (ETC) interference and synergistic adjuvant therapy". Density functional theory calculations revealed that the synergistic effect among multi-enzyme active centers endows the AFCT nanozymes with excellent catalytic activity. In TME, open sources of H2O2 can be achieved by superoxide dismutase-mimicking AFCT nanozymes. In response to the dual stimuli of H2O2 and mild acidity, the peroxidase-mimicking activity of AFCT nanozymes not only catalyzes the accumulation of H2O2 to generate ·OH but also converts the loaded 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) into its oxidized form with strong near-infrared absorption, specifically unlocking its photothermal and photoacoustic imaging properties. Intriguingly, the undesired thermoresistance of tumor cells can be greatly alleviated owing to the reduced expression of heat shock proteins enabled by NADH POD-mimicking AFCT-mediated NADH depletion and consequent restriction of ATP supply. Meanwhile, the accumulated ·OH can facilitate both apoptosis and ferroptosis in tumor cells, resulting in synergistic therapeutic outcomes in combination with TME-activated mild PTT.

Tumor-Specific NIR-Activatable Nanoreactor for Self-Enhanced Multimodal Imaging and Cancer Phototherapy.

Responsive nanosystems for tumor treatment with high specificity and sensitivity have aroused great attention. Herein, we develop a tumor microenvironment responsive and near-infrared (NIR)-activatable theranostic nanoreactor for imaging-guided anticancer therapy. The nanoreactor (SnO2-x@AGP) is comprised of poly(vinylpyrrolidine) encapsulated hollow mesoporous black SnO2-x nanoparticles coloaded with glucose oxidase (GOx) and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). The constructed nanoreactor can be specifically activated through endogenous H2O2 by an NIR-mediated "bursting-like" process to enhance its imaging and therapeutic functions. Black SnO2-x with abundant oxygen vacancies expedites effective separation of electron-hole pairs from energy-band structure and endows them with strong hyperthermia effect upon NIR laser irradiation. The generating toxic H2O2 with the assistance of GOx provides SnO2-x@AGP with the capacity of oxidative stress therapy. Ascended H2O2 can activate ABTS into ABTS•+. ABTS•+ not only possesses significant NIR absorption properties, but also disrupts intracellular glutathione to generate excessive reactive oxygen species for improved phototherapy, leading to more effective treatment together with oxidative stress therapy. Thus, SnO2-x@AGP with NIR-mediated and H2O2-activated performance presents tumor inhibition efficacy with minimized damage to normal tissues. These outstanding characteristics of SnO2-x@AGP bring an insight into the development of activatable nanoreactors for smart, precise, and non-invasive cancer theranostics.

Effect of Roy's Adaptation, Model-based, Perioperative Nursing Service on Patients: A Clinical Observational Study.

Context: Surgery for early-stage lung carcinoma (LC) is invasive and most patients will experience psychological disorders, such as depression and anxiety. Accumulating evidence has shown that a nursing intervention can exert significant improvements in clinical efficacy for perioperative patients. Objective: The study intended to investigate the clinical value during the perioperative period of a nursing service based on Roy's Adaptation Model (RAM), for patients undergoing radical resection for early-stage LC, to provide accurate guidance and reference for a future clinical nursing intervention for LC patients. Design: The research team designed a retrospective analysis, controlled study. Setting: The study took place at Jiangsu Cancer Hospital in Nanjing, Jiangsu, China. Participants: Participants were 69 patients with early-stage LC who had been admitted to the hospital between March 2018 and March 2020. Intervention: The research team assigned participants to an intervention or a control group, with 42 participants in the intervention group receiving RAM nursing during hospitalization, and 27 participants in the control group receiving routine nursing care. Outcome Measures: The study measured the alterations in pulmonary function (PF) pre- and postoperatively and assessed the incidence of complications postintervention. At baseline and postintervention, the research team also assessed participants' psychological states using the Self-rating Anxiety Scale (SAS) and the Self-rating Depression Scale (SDS) and their pain levels using a visual analogue scale (VAS). Postintervention, participants competed a nursing satisfaction survey. At baseline and postintervention, the participants completed the Karnofsky Performance Status (KPS) scale for functional status, the Self-Perceived Burden Scale in Cancer Patients (SPBS-CP), the Pittsburgh Sleep Quality Index (PSQI) for sleep quality, and the WHO-QOL-BREF questionnaire. Results: Postoperatively, the PF indexes had decreased significantly for both groups, but the intervention group's value were significantly higher postoperatively than those in the control group (P < .05). No differences existed in the incidence of adverse reactions between the groups (P > .05). The intervention group had significantly lower SAS and SDS scores, pain scores, and SPBS-CP scores than the control group postintervention but had significantly higher KPS scores (all P < .05). The intervention group significantly higher nursing satisfaction, sleep quality, and quality of life than the control group did (P < .05). Conclusions: RAM nursing can significantly protect the PF of patients with early-stage LC who are undergoing a radical resection and can effectively improve patients' psychological states, sleep quality, and nursing satisfaction, which makes it worthy of clinical reference and popularization.

Alternative Strategy to Optimize Cerium Oxide for Enhanced X-ray-Induced Photodynamic Therapy.

The emergence of X-ray-induced photodynamic therapy (X-PDT) holds tremendous promise for clinical deep-penetrating cancer therapy. However, the clinical application of X-PDT in cancer treatment is still limited due to the hypoxic property of cancerous tissue, the inherent antioxidant system of tumor cells, and the difficulty in matching the absorption spectra of photosensitizers. Herein, a versatile core-shell radiosensitizer (SCNPs@DMSN@CeOx-PEG, denoted as SSCP) was elaborately designed and constructed to enhance X-PDT by coating tunable mesoporous silica on nanoscintillators, followed by embedding the cerium oxide nanoparticles in situ. The obtained SSCP radiosensitizer demonstrated a distinct blue-shift in the ultraviolet light region, so that it could perfectly absorb the ultraviolet light converted by the SCNPs core, resulting in the formation of photoinduced electron-hole (e--h+) pairs separation to generate reactive oxygen species (ROS). In addition, the cerium oxide exhibits high glutathione consumption to heighten ROS accumulation, and catalase-like activity to alleviate the hypoxia, which further enhances the efficiency of radiotherapy. Benefiting from the abundant Lu and Ce elements, the computed tomography imaging performance of SSCP is about 3.79-fold that of the clinical contrast agent (iohexol), which has great potential in both preclinical imaging and clinical translation.

Dual Glutathione Depletion Enhanced Enzyme Catalytic Activity for Hyperthermia Assisted Tumor Therapy on Semi-Metallic VSe2/Mn-CS.

Semimetallic nanomaterials as photothermal agents for bioimaging and cancer therapy have attracted tremendous interest. However, the poor photothermal stability, low biocompatibility, and single component limit their therapeutic efficiency in cancer treatment. Here, manganese-doped VSe2 semimetallic nanosheets were prepared and subsequently modified with chitosan (named VSe2/Mn-CS NSs) for combined enzyme catalytic and photothermal therapy. VSe2/Mn-CS NSs show high photothermal property with a photothermal conversion efficiency of 34.61% upon 808 nm near-infrared laser irradiation. In the tumor microenvironment, VSe2/Mn-CS NSs can convert endogenous H2O2 into lethal hydroxyl radicals (•OH) to induce cancer cell apoptosis. The interaction between glutathione (GSH) and Se-Se bonds in VSe2/Mn-CS NSs results in the depletion of GSH level, and the valence states transition of manganese ions is also beneficial for the GSH consumption. This dual depletion of GSH markedly enhances the peroxidase (POD) activity, leading to the high •OH production and the improved therapeutic effect. What is more, the T1-weighted magnetic resonance and photoacoustic imaging endow VSe2/Mn-CS NSs with the ability to guide and track the treatment process. Our study provides a research strategy for the application of semimetallic nanomaterials in cancer diagnosis and treatment.

Near Infrared-Triggered Theranostic Nanoplatform with Controlled Release of HSP90 Inhibitor for Synergistic Mild Photothermal and Enhanced Nanocatalytic Therapy with Hypoxia Relief.

Mild photothermal therapy (PTT, <45 °C) can prevent tumor metastasis and heat damage to normal tissue, compared with traditional PTT (>50 °C). However, its therapeutic efficacy is limited owing to the hypoxic tumor environment and tumor thermoresistance owing to the overproduction of heat shock proteins (HSPs). Herein, a near-infrared (NIR)-triggered theranostic nanoplatform (GA-PB@MONs@LA) is designed for synergistic mild PTT and enhanced Fenton nanocatalytic therapy against hypoxic tumors. The nanoplatform is fabricated by the confined formation of Prussian blue (PB) nanoparticles in mesoporous organosilica nanoparticles (MONs), followed by the loading of gambogic acid (GA), an HSP90 inhibitor, and coating with thermo-sensitive lauric acid (LA). Upon NIR irradiation, the photothermal effect (44 °C) of PB not only induces apoptosis of tumor cells but also triggers the on-demand release of GA, inhibiting the production of HSP90. Moreover, the delivered heat simultaneously enhances the catalase-like and Fenton activity of PB@MONs@LA in an acidic tumor microenvironment, relieving the tumor hypoxia and promoting the generation of highly toxic •OH. In addition, the nanoplatform enables magnetic resonance/photoacoustic dual-modal imaging. Thus, this study describes a distinctive paradigm for the development of NIR-triggered theranostic nanoplatforms for enhanced cancer therapy.

Pt Decorated Ti3C2Tx MXene with NIR-II Light Amplified Nanozyme Catalytic Activity for Efficient Phototheranostics.

The clinical application of photothermal therapy (PTT) is severely limited by the tissue penetration depth of excitation light, and enzyme therapy is hampered by its low therapeutic efficiency. As a two-dimensional ultrathin nanosheet with high absorbance in the near-infrared-II (NIR-II) region, the titanium carbide (Ti3C2) nanosheet can be used as a substrate to anchor functional components, like nanozymes and nanodrugs. Here, we decorate Pt artificial nanozymes on the Ti3C2 nanosheets to synthesize Ti-based MXene nanocomposites (Ti3C2Tx-Pt-PEG). In the tumor microenvironment, the Pt nanoparticles exhibit peroxidase-like (POD-like) activity, which can in situ catalyze hydrogen peroxide to generate hydroxyl radicals (•OH) to induce cell apoptosis and necrosis. Meanwhile, the composite shows a desirable photothermal effect upon NIR-II light irradiation with a low power density (0.75 W cm-2). Especially, the POD-like activity is significantly enhanced by the elevated temperature arising from the photothermal effect of Ti3C2Tx. Therefore, satisfactory synergistic PTT/enzyme therapy has been accomplished, accompanied by an applicable photoacoustic imaging capability to monitor and guide the therapeutic process. This work may provide an approach for hyperthermia-amplified nanozyme catalytic therapy, especially based on metal catalysts and MXene nanocomposites.

Near-Infrared Upconversion Mesoporous Tin Dioxide Theranostic Nanocapsules for Synergetic Cancer Chemophototherapy.

Smart nanotheranostic systems (SNSs) have attracted extensive attention in antitumor therapy. Nevertheless, constructing SNSs with disease diagnosis ability, improved drug delivery efficiency, inherent imaging performance, and high treatment efficiency remains a scientific challenge. Herein, ultrasmall tin dioxide (SnO2) was assembled with upconversion nanoparticles (UCNPs) to form mesoporous nanocapsules by an in situ hydrothermal deposition method, followed by loading with doxorubicin (DOX) and modification with bovine serum albumin (BSA). pH/near-infrared dual-responsive nanotheranostics was constructed for computed tomography (CT) and magnetic resonance (MR) imaging-induced collaborative cancer treatment. The mesoporous channel of SnO2 was utilized as a reservoir to encapsulate DOX, an antineoplastic drug, for chemotherapy and as a semiconductor photosensitizer for photodynamic therapy (PDT). Furthermore, the DOX-loaded UCNPs@SnO2-BSA nanocapsules combined PDT, Nd3+-doped UCNP-triggered hyperthermia effect, and DOX-triggered chemotherapy simultaneously and demonstrated prominently enhanced treatment efficiency compared to the monotherapy model. Moreover, tin, as one of the trace elements in the human body, has a similar X-ray attenuation coefficient to iodine and therefore can act as a contrast agent for CT imaging to monitor the treatment process. Such an orchestrated synergistic anticancer treatment exhibited apparent inhibition of tumor growth in tumor-bearing mice with negligible side effects. Our study demonstrates nanocapsules with excellent biocompatibility and great potential for cancer treatment.

College of American Pathologists Tumor Regression Grading System for Long-Term Outcome in Patients with Locally Advanced Rectal Cancer.

BACKGROUND: The National Comprehensive Cancer Network's Rectal Cancer Guideline Panel recommends American Joint Committee of Cancer and College of American Pathologists (AJCC/CAP) tumor regression grading (TRG) system to evaluate pathologic response to neoadjuvant chemoradiotherapy for locally advanced rectal cancer (LARC). Yet, the clinical significance of the AJCC/CAP TRG system has not been fully defined. MATERIALS AND METHODS: This was a multicenter, retrospectively recruited, and prospectively maintained cohort study. Patients with LARC from one institution formed the discovery set, and cases from external independent institutions formed a validation set to verify the findings from discovery set. Overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were assessed by Kaplan-Meier analysis, log-rank test, and Cox regression model. RESULTS: The discovery set (940 cases) found, and the validation set (2,156 cases) further confirmed, that inferior AJCC/CAP TRG categories were closely /ccorrelated with unfavorable survival (OS, DFS, LRFS, and DMFS) and higher risk of disease progression (death, accumulative relapse, local recurrence, and distant metastasis) (all p < .05). Significantly, pairwise comparison revealed that any two of four TRG categories had the distinguished survival and risk of disease progression. After propensity score matching, AJCC/CAP TRG0 category (pathological complete response) patients treated with or without adjuvant chemotherapy displayed similar survival of OS, DFS, LRFS, and DMFS (all p > .05). For AJCC/CAP TRG1-3 cases, adjuvant chemotherapy treatment significantly improved 3-year OS (90.2% vs. 84.6%, p < .001). Multivariate analysis demonstrated the AJCC/CAP TRG system was an independent prognostic surrogate. CONCLUSION: AJCC/CAP TRG system, an accurate prognostic surrogate, appears ideal for further strategizing adjuvant chemotherapy for LARC. IMPLICATIONS FOR PRACTICE: The National Comprehensive Cancer Network recommends the American Joint Committee of Cancer and College of American Pathologists (AJCC/CAP) tumor regression grading (TRG) four-category system to evaluate the pathologic response to neoadjuvant treatment for patients with locally advanced rectal cancer; however, the clinical significance of the AJCC/CAP TRG system has not yet been clearly addressed. This study found, for the first time, that any two of four AJCC/CAP TRG categories had the distinguished long-term survival outcome. Importantly, adjuvant chemotherapy may improve the 3-year overall survival for AJCC/CAP TRG1-3 category patients but not for AJCC/CAP TRG0 category patients. Thus, AJCC/CAP TRG system, an accurate surrogate of long-term survival outcome, is useful in guiding adjuvant chemotherapy management for rectal cancer.

Intelligent Fe-Mn Layered Double Hydroxides Nanosheets Anchored with Upconversion Nanoparticles for Oxygen-Elevated Synergetic Therapy and Bioimaging.

Multimodal synergistic therapy based on photodynamic therapy (PDT), photothermal therapy (PTT), and chemodynamic therapy (CDT) has attracted increasing attention in cancer therapy. However, the scant therapeutic efficiency is always a barrier for further application. Herein, a smart tumor microenvironment (TME) responsive nanocatalysts are developed by adopting Fe-Mn layered double hydroxides (FeMn-LDH) as an effective photothermal nanocarrier to load mesoporous silica and chlorin e6 (Ce6)-covalently coated upconversion nanoparticles (UCSP) for multimodal imaging for directed therapy. Under acidic TME, FeMn-LDH degrades into Fe3+ and Mn2+ ions to initiate a Fenton-like reaction inducing CDT and enhancing magnetic resonance imaging. Additionally, Fe3+ can decompose H2 O2 to oxygen (O2 ), enhancing PDT guided by UCSP. As a representative noninvasive imaging probe, the upconversion luminescence will recover after decomposition of FeMn-LDH, and provide high-resolution upconversion luminescent imaging guidance for pinpointed PDT. Moreover, the photothermal properties of FeMn-LDH can further enhance CDT effects. The synergistic therapy and multifunctional imaging can realize the integration of diagnosis and treatment.

Determination of vitamin D3 in daily oily supplements by a two-dimensional supercritical fluid chromatography-liquid chromatography-mass spectrometry system.

A two-dimensional system composed of supercritical fluid chromatography (SFC) and reverse phase liquid chromatography (RPLC) coupled a tandem mass spectrometry (MS) was developed for the quantitative analysis of vitamin D in daily oily supplements. Two six-port switching valves are configured, allowing four different valve positions. When the valve positions were fixed at Position A, this system worked at SFC-MS mode. When the valve positions switched between Position B and C, this system worked at a SFC-LC-MS switching mode. Vitamin D3 in two kinds of oily drops, Baby Ddrops and Vitamin AD drops, was determined at both SFC-MS and SFC-LC-MS switching modes by using the same system. The linearity, repeatability and recovery were investigated using the internal and external standard methods for the two modes. The results obtained from the internal standard method are better than those of the external standard method at either mode. The coefficient of determination (r2) for the internal standard method is more than 0.999, with a linear range of 20-1000 µg/L. Both Baby Ddrops and Vitamin AD drops were analyzed with good repeatability (<3.21%) and recovery (94.1%-116.1%) using internal standard method. When calculated by the external standard method, as compared to SFC-MS mode, SFC-LC-MS switching mode has better linearity (r2>0.999), repeatability (Baby Ddrops: 4.45%, Vitamin AD drops: 1.12%) and recovery (86.3%-107.1%). The results indicate that the two-dimensional SFC-MS/SFC-LC-MS system is useful for determination of vitamin D in oily drops. If it works at SFC-MS mode, the internal standard is required. When SFC-LC-MS switching mode is used, external standard method can also obtain the accurate results with good precision.

The yin and yang functions of extracellular ATP and adenosine in tumor immunity.

Extracellular adenosine triphosphate (eATP) and its main metabolite adenosine (ADO) constitute an intrinsic part of immunological network in tumor immunity. The concentrations of eATP and ADO in tumor microenvironment (TME) are controlled by ectonucleotidases, such as CD39 and CD73, the major ecto-enzymes expressed on immune cells, endothelial cells and cancer cells. Once accumulated in TME, eATP boosts antitumor immune responses, while ADO attenuates immunity against tumors. eATP and ADO, like yin and yang, represent two opposite aspects from immune-activating to immune-suppressive signals. Here we reviewed the functions of eATP and ADO in tumor immunity and attempt to block eATP hydrolysis, ADO formation and their contradictory effects in tumor models, allowing the induction of effective anti-tumor immune responses in TME. These attempts documented that therapeutic approaches targeting eATP/ADO metabolism and function may be effective methods in cancer therapy.

Hyperthermia and Controllable Free Radical Coenhanced Synergistic Therapy in Hypoxia Enabled by Near-Infrared-II Light Irradiation.

Tumor cell metabolism and tumor blood vessel proliferation are distinct from normal cells. The resulting tumor microenvironment presents a characteristic of hypoxia, which greatly limits the generation of oxygen free radicals and affects the therapeutic effect of photodynamic therapy. Here, we developed an oxygen-independent free radical generated nanosystem (CuFeSe2-AIPH@BSA) with dual-peak absorption in both near-infrared (NIR) regions and utilized it for imaging-guided synergistic treatment. The special absorption provides the nanosystem with high photothermal conversion efficiency and favorably matched photoactivity in both I and II NIR biological windows. Upon NIR light irradiation, the generated heat could prompt AIPH release and decompose to produce oxygen-independent free radicals for killing cancer cells effectively. The contrastive research results show that the enhanced therapeutic efficacy of NIR-II over NIR-I is principally due to its deeper tissue penetration and higher maximum permission exposure that benefits from a longer wavelength. Hyperthermia effect and the production of toxic free radicals upon NIR-II laser illumination are extremely effective in triggering apoptosis and death of cancer cells in the tumor hypoxia microenvironment. The high biocompatibility and excellent anticancer efficiency of CuFeSe2-AIPH@BSA allow it to be an ideal oxygen-independent nanosystem for imaging-guided and NIR-II-mediated synergistic therapy via systemic administration.

5, 7, 2', 4', 5'-Pentamethoxyflavanone regulates M1/M2 macrophage phenotype and protects the septic mice.

Flavonoids have been reported to exert protective effect against many inflammatory diseases, while the underlying cellular mechanisms are still not completely known. In the present study, we explored the anti-inflammation activity of 5, 7, 2', 4', 5'-pentamethoxyflavanone (abbreviated as Pen.), a kind of polymethoxylated flavonoid, both in vitro and in vivo experiments. Pen. was showed no obvious toxicity in macrophages even at high dosage treatment. Our results indicated that Pen. significantly inhibited both mRNA and protein level of proinflammatory cytokines, IL-1ß, IL-6, TNF-α and iNOS, which was characteristic expressed on M1 polarized macrophages. These effects of Pen. were further confirmed by diminished expression of CD11c, the M1 macrophage surface marker. Further researches showed that the mechanism was due to that Pen. downregulated the activity of p65, key transcription factor for M1 polarization. On the other hand, Pen. also enhanced M2 polarization with upregulation of anti-inflammatory factors and increase of M2 macrophage surface markers, which lead to the balance of M1 and M2 macrophages. Moreover, in vivo research verified that Pen. treatment alleviated LPS-induced sepsis in mice by increasing survival rate, decreasing inflammatory cytokines and improving lung tissue damage. In summary, our results suggested that Pen. modulated macrophage phenotype via suppressing p65 signal pathway to exert the anti-inflammation activity.

Magnetic Targeting, Tumor Microenvironment-Responsive Intelligent Nanocatalysts for Enhanced Tumor Ablation.

Therapeutic nanosystems which can be triggered by the distinctive tumor microenvironment possess great selectivity and safety to treat cancers via in situ transformation of nontoxic prodrugs into toxic therapeutic agents. Here, we constructed intelligent, magnetic targeting, and tumor microenvironment-responsive nanocatalysts that can acquire oxidation therapy of cancer via specific reaction at tumor site. The magnetic nanoparticle core of iron carbide-glucose oxidase (Fe5C2-GOD) achieved by physical absorption has a high enzyme payload, and the manganese dioxide (MnO2) nanoshell as an intelligent "gatekeeper" shields GOD from premature leaking until reaching tumor tissue. Fe5C2-GOD@MnO2 nanocatalysts maintained inactive in normal cells upon systemic administration. On the contrary, after endocytosis by tumor cells, tumor acidic microenvironment induced decomposition of MnO2 nanoshell into Mn2+ and O2, meanwhile releasing GOD. Mn2+ could serve as a magnetic resonance imaging (MRI) contrast agent for real-time monitoring treatment process. Then the generated O2 and released GOD in nanocatalysts could effectively exhaust glucose in tumor cells, simultaneously generating plenty of H2O2 which may accelerate the subsequent Fenton reaction catalyzed by the Fe5C2 magnetic core in mildly acidic tumor microenvironments. Finally, we demonstrated the tumor site-specific production of highly toxic hydroxyl radicals for enhanced anticancer therapeutic efficacy while minimizing systemic toxicity in mice.

Multifunctional Theranostic Nanoplatform Based on Fe-mTa2O5@CuS-ZnPc/PCM for Bimodal Imaging and Synergistically Enhanced Phototherapy.

Multifunctional nanotheranostic agent with high performance for tumor site-specific generation of singlet oxygen (1O2) as well as imaging-guidance is crucial to laser-mediated photodynamic therapy. Here, we introduced a versatile strategy to design a smart nanoplatform using phase change material (PCM) to encapsulate photosensitizer (zinc phthalocyanine, ZnPc) in copper sulfide loaded Fe-doped tantalum oxide (Fe-mTa2O5@CuS) nanoparticles. When irradiated by 808 nm laser, the PCM is melted due to the hyperthermia effect from CuS nanoparticles, inducing the release of ZnPc to produce toxic 1O2 triggered by 650 nm light with very low power density (5 mW/cm2). Then, the produced heat and toxic 1O2 can kill tumor cells in vitro and in vivo effectively. Furthermore, the special properties of Fe-mTa2O5 endow the nanoplatform with excellent computed tomography (CT) and T1-weighted magnetic resonance imaging ( T1-MRI) performance for guiding and real-time monitoring of therapeutic effect. This work presents a feasible way to design smart nanoplatform for controllable generation of heat and 1O2, achieving CT/ T1-MRI dual-modal imaging-guided phototherapy.

Anti-angiogenic effects of Qingdu granule on breast cancer through inhibiting NFAT signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Qingdu granule (QDG), a traditional Chinese herbal prescription, had anti-tumor effect on breast cancer. However the underlying mechanism of QDG was unclear. THE AIM OF THIS STUDY: The present study aimed to investigate whether QDG could inhibit angiogenesis of breast cancer via acting on nuclear factor of activated T-cells (NFAT) signaling pathway. This was implicated in human umbilical vein endothelial cells (HUVECs) in vitro and breast cancer xenograft model in vivo. MATERIALS AND METHODS: The VEGF165 (15.58 ng/mL) induced human umbilical vein endothelial cells (HUVECs) were treated with serum samples containing tamoxifen (TAM), tacrolimus (FK506), or QDG with three dosages. The migration and canalization capacities of HUVECs were evaluated by transwell migration and tube formation assay. In 72 h-cultured HUVECs, The gene expression, protein amount, and nuclear translocation of NFATc3 were measured. The anti-tumor and anti-angiogenic effects of QDG in vivo were investigated in breast cancer xenograft model. The serum VEGF levels, microvessel density, and protein expressions (immunohistochemistry and western blot) of VEGF, VEGFR2 and NFATc3 were detected. RESULTS: The results showed that, QDG significantly inhibited HUVEC migration and tube formation. It downregulated NFATc3 gene expression, decreased NFATc3 protein amount, and reduced the ratio of NFATc3 nuclear translocation in HUVECs. In breast cancer xenograft model, QDG treatment significantly suppressed tumor growth, inhibited VEGF release, and decreased microvessel density. QDG reduced protein expressions of VEGF, VEGFR2 and NFATc3. CONCLUSION: The results suggested that QDG showed anti-angiogenic effects of breast cancer both in vitro and in vivo. The mechanism might be partially associated with inhibiting NFAT signaling pathway.