Glutathione-triggered release of SO2 gas to augment oxidative stress for enhanced chemodynamic and sonodynamic therapy.

Recently, gas therapy has emerged as a promising alternative treatment for deep-seated tumors. However, some challenges regarding insufficient or uncontrolled gas generation as well as unclear therapeutic mechanisms restrict its further clinical application. Herein, a well-designed nanoreactor based on intracellular glutathione (GSH)-triggered generation of sulfur dioxide (SO2) gas to augment oxidative stress has been developed for synergistic chemodynamic therapy (CDT)/sonodynamic therapy (SDT)/SO2 gas therapy. The nanoreactor (designed as CCM@FH-DNs) is constructed by employing iron-doped hollow mesoporous silica nanoparticles as carriers, the surface of which was modified with the SO2 prodrug 2,4-dinitrobenzenesulfonyl (DNs) and further coated with cancer cell membranes for homologous targeting. The CCM@FH-DNs can not only serve as a Fenton-like agent for CDT, but also as a sonosensitizer for SDT. Importantly, CCM@FH-DNs can release SO2 for SO2-mediated gas therapy. Both in vitro and in vivo evaluations demonstrate that the CCM@FH-DNs nanoreactor performs well in augmenting oxidative stress for SO2 gas therapy-enhanced CDT/SDT via GSH depletion and glutathione peroxidase-4 enzyme deactivation as well as superoxide dismutase inhibition. Moreover, the doped iron ions ensure that the CCM@FH-DNs nanoreactors enable magnetic resonance imaging-guided therapy. Such a GSH-triggered SO2 gas therapy-enhanced CDT/SDT strategy provides an intelligent paradigm for developing efficient tumor microenvironment-responsive treatments.

The efficacy and safety of vonoprazan-amoxicillin dual therapy in eradicating Helicobacter pylori: a systematic review and meta-analysis.

AIM: To evaluate the efficacy and safety of vonoprazan-amoxicillin (VA) dual therapy for radically eradicating Helicobacter pylori (H. pylori). METHODS: The PubMed, Cochrane Library, Embase, China National Knowledge  Infrastructure (CNKI) and Wanfang databases were searched up to July 7, 2022, to identify clinical trials comparing the efficacy of VA dual therapy and triple therapy for H. pylori eradication. After evaluating the quality of the included studies, random effects models were conducted, and risk ratios (RRs) with 95% confidence intervals (CIs) were calculated to estimate the efficacy and safety of each approach. RESULTS: Six publications (including four randomized controlled trials) involving 2019 patients were included in this meta-analysis. Overall, the eradication rate for VA dual therapy was 89.9%, while it was 85.2% for triple therapy based on other acid inhibitors. The eradication rate of H. pylori in the VA dual regimen group was higher than that in the PPI-based (omeprazole or lansoprazole) triple therapy group (RR = 1.15, 95% CI 1.07-1.23, p < 0.0001). However, the efficacy of VA dual therapy was comparable with VA-Clarithromycin (VAC) triple therapy (RR = 0.97, 95% CI 0.93-1.02). Besides, the incidence of adverse reactions in VA dual therapy was also lower than that in triple therapy (RR = 0.80, 95% CI 0.70-0.91, p = 0.0009). CONCLUSION: Compared with PPI-based triple therapy, VA dual therapy showed a better therapeutic effect, safety and patient compliance rate for eradicating H. pylori, which should be used as a novel curative strategy in the future.

Insight into the acid tolerance mechanism of Acetilactobacillus jinshanensis subsp. aerogenes Z-1.

Several lactic acid bacteria (LAB) are double-edged swords in the production of Sichuan bran vinegar; on the one hand, they are important for the flavour of the vinegar, but on the other hand, they result in vinegar deterioration because of their gas-producing features and their acid resistance. These characteristics intensify the difficulty in managing the safe production of vinegar using strains such as Acetilactobacillus jinshanensis subsp. aerogenes Z-1. Therefore, it is necessary to characterize the mechanisms underlying their acid tolerance. The results of this study showed a survival rate of 77.2% for Z-1 when exposed to pH 3.0 stress for 1 h. This strain could survive for approximately 15 days in a vinegar solution with 4% or 6% total acid content, and its growth was effectively enhanced by the addition of 10 mM of arginine (Arg). Under acidic stress, the relative content of the unsaturated fatty acid C18:1 (n-11) increased, and eight amino acids accumulated in the cells. Meanwhile, based on a transcriptome analysis, the genes glnA, carA/B, arcA, murE/F/G, fabD/H/G, DnaK, uvrA, opuA/C, fliy, ecfA2, dnaA and LuxS, mainly enriched in amino acid transport and metabolism, protein folding, DNA repair, and cell wall/membrane metabolism processes, were hypothesized to be acid resistance-related genes in Z-1. This work paves the way for further clarifying the acid tolerance mechanism of Z-1 and shares applicable perspectives for vinegar brewing.

Reactive oxygen species nanoamplifiers with multi-enzymatic activities for enhanced tumor therapy.

The ingenious combination of nano-enzymes with multi-enzyme activities and therapeutic drugs that can promote reactive oxygen species (ROS) production in cancer cells will enhance the therapeutic efficacy of nanomedicines on malignant tumors by amplifying oxidative stress. Herein, PEGylated Ce-doped hollow mesoporous silica nanoparticles (Ce-HMSN-PEG) loaded with saikosaponin A (SSA) are elaborately constructed as a smart nanoplatform for improving the efficiency of tumor therapy. The carrier Ce-HMSN-PEG showed multi-enzyme activities due to the presence of mixed Ce3+/Ce4+ ions. In the tumor microenvironment, peroxidase-like Ce3+ ions convert endogenous H2O2 into highly toxic ˙OH for chemodynamic therapy, while Ce4+ ions not only show catalase-like activity to reduce tumor hypoxia but also exhibit glutathione (GSH) peroxidase-mimicking properties to effectively deplete GSH in tumor cells. Moreover, the loaded SSA can cause the enrichment of superoxide anions (˙O2-) and H2O2 within tumor cells by disrupting mitochondrial functions. By integrating the respective advantages of Ce-HMSN-PEG and SSA, the as-prepared SSA@Ce-HMSN-PEG nanoplatform can efficiently trigger cancer cell death and inhibit tumor growth via significantly enhanced ROS production. Therefore, this positive combination therapy strategy has a good application prospect for enhancing antitumor efficacy.

Prognosis value of serum chloride on 1-year mortality in cirrhotic patients receiving transjugular intrahepatic portosystemic shunt.

BACKGROUND AND PURPOSE: Emerging researches have regarded serum chloride as a capable predictor of mortality in liver cirrhosis. We aim to investigate the clinical role of admission chloride in cirrhotic patients with esophagogastric varices receiving transjugular intrahepatic portosystemic shunt (TIPS), which is unclear. METHODS: We retrospectively analyzed data of cirrhotic patients with esophagogastric varices undergoing TIPS in Zhongnan Hospital of Wuhan University. Mortality outcome was obtained by following up for 1-year after TIPS. Univariate and multivariate Cox regression were used to identify independent predictors of 1-year mortality post-TIPS. The receiver operating characteristic (ROC) curves were adopted to assess the predictive ability of the predictors. In addition, log-rank test and Kaplan-Meier (KM) analyses were employed to evaluate the prognostic value of predictors in the survival probability. RESULTS: A total of 182 patients were included ultimately. Age, fever symptom, platelet-to lymphocyte-ratio (PLR), lymphocyte-to-monocyte ratio (LMR), total bilirubin, serum sodium, chloride, and Child-Pugh score were related to 1-year follow-up mortality. In multivariate Cox regression analysis, serum chloride (HR = 0.823, 95%CI = 0.757-0.894, p < 0.001) and Child-Pugh score (HR = 1.401, 95%CI = 1.151-1.704, p = 0.001) were identified as independent predictors of 1-year mortality. Patients with serum chloride <107.35 mmol/L showed worse survival probability than those with serum chloride ≥107.35 mmol/L no matter with or without ascites (p < 0.05). CONCLUSION: Admission hypochloremia and increasing Child-Pugh score are independent predictors of 1-year mortality in cirrhotic patients with esophagogastric varices receiving TIPS.

Isolation and characterization of a gas-producing and acid-resistant bacterium from spoiled vinegar.

To understand the deterioration of vinegar that has frequently occurred in China recently and to address such a concern, the physicochemical indicators and bacterial structure of the spoiled vinegar collected from Sichuan were preliminarily investigated. Results showed that Lactobacillaceae was most likely responsible for the decrease of vinegar total sugar and furfural, through which total acid and furfuryl alcohol were generated. Then, an unreported difficult-to-cultivate gas-producing bacterium named Z-1 was isolated using a modified MRS medium. Strain Z-1 was identified as Acetilactobacillus jinshanensis subsp. aerogenes on the basis of physiological, biochemical, molecular biological and whole genome analyses. According to the investigation, such species was present throughout the fermentation process and not limited in Sichuan. The analysis of genetic diversity indicated that all the obtained A. jinshanensis isolates displayed high sequence similarity and an absence of recombination. Although it demonstrated acid resistance, Z-1 could be completely deactivated through heating (60 °C). Based on the above results, suggestions for safe production are made for vinegar enterprises.

Molecular and Clinical Characteristics of Carbapenem-Resistant Klebsiella pneumoniae Isolates at a Tertiary Hospital in Wuhan, China.

Background: Carbapenem resistant Klebsiella pneumoniae (CRKP) is an independent risk factor for nosocomial infection which poses a serious threat to human health. How to prevent and suppress CRKP infection and explore its drug resistance mechanisms have become a huge challenge and possesses immediate significance. Methods: A total of 45 CRKP strains isolated from hospitalized patients in Zhongnan Hospital of Wuhan University were collected from August 2018-December 2020. The strain's identification and antimicrobial susceptibility tests were performed using the VITEK 2 automated identification instrument. Single molecule DNA sequencing of 45 CRKP isolates was performed by the third generation high-throughput sequencing technology. Results: The results were analyzed by multi locus sequence typing (MLST) and phylogenetic analysis. Antimicrobial susceptibility showed that 45 CRKP isolates were multi-drug resistant strains, and the resistance rates to common antibiotics were as high as 68%. Whole genome sequencing results showed that the CRKP strains carried multiple drug resistance genes and virulence factors. MLST analysis found two different sequence types (ST), of which 44 were ST11 and 1 was ST1049. Conclusion: Through whole genome sequencing (WGS), we found multiple drug-resistant genes and virulence factors, and there was obvious dominant microbiota. The source was mainly related to nosocomial infection. The ST11-KPC Klebsiella pneumoniae was the main type, which was consistent with the most common type in China. We identified several dominant microbiotas which may serve as a target in the clinical prevention and treatment of severe bacterial infections. Our finding may have a role for guiding clinical antibiotic choosing.

Modulation of hypoxia and redox in the solid tumor microenvironment with a catalytic nanoplatform to enhance combinational chemodynamic/sonodynamic therapy.

The efficacy of reactive oxygen species-mediated therapy is generally limited by hypoxia and overexpressed glutathione (GSH) in the tumor microenvironment (TME). To address these issues, herein, a smart Mn3O4/OCN-PpIX@BSA nanoplatform is rationally developed to enhance the combinational therapeutic efficacy of chemodynamic therapy (CDT) and sonodynamic therapy (SDT) through TME modulation. For constructing the catalytic nanoplatform (Mn3O4/OCN-PpIX@BSA), Mn3O4 nanoparticles were grown in situ on oxidized g-C3N4 (OCN) nanosheets, and the as-prepared Mn3O4/OCN nano-hybrids were then successively loaded with protoporphyrin (PpIX) and coated with bovine serum albumin (BSA). The catalase-like Mn3O4 nanoparticles are able to effectively catalyze the overexpressed endogenous H2O2 to produce O2, which could relieve hypoxia and improve the therapeutic effect of combinational CDT/SDT. The decomposition of Mn3O4 by GSH enables the release of Mn2+ ions, which not only facilitates good T1/T2 dual-modal magnetic resonance imaging for tumor localization but also results in the depletion of GSH and the Mn2+-driven Fenton-like reaction, thus further amplifying the oxidative stress and achieving improved therapeutic efficacy. It is worth noting that the Mn3O4/OCN-PpIX@BSA nanocomposites exhibit minimal toxicity to normal tissues at therapeutic doses. These positive findings provide a new strategy for the convenient construction of TME-regulating smart theranostic nanoagents to improve the therapeutic outcomes towards malignant tumors effectively.

An Ultrasound-Triggered Nanoplatform for Synergistic Sonodynamic-Nitric Oxide Therapy.

Ultrasound (US)-triggered sonodynamic therapy (SDT) has aroused intensive interest as a powerful alternative for cancer treatment in recent years due to its non-invasiveness and deep tissue penetration. However, the therapeutic effect of SDT alone is still limited by intrinsic hypoxia in solid tumors. Combined synergistic therapy strategies are highly desired for improving therapeutic efficiency. Herein, a rationally designed intelligent theranostic nanoplatform is developed for the enhancement of cancer treatment through synergistic SDT and nitric oxide (NO) therapy. This US-triggered nanoplatform is fabricated by integrating a sonosensitizer Rose Bengal (RB) and a NO donor (SNO) into manganese-doped hollow mesoporous silica nanoparticles (MH-SNO@RB). Impressively, the acidic and reducing tumor microenvironment accelerates the sustainable release of Mn ions from the framework, which facilitates the MH-SNO@RB to be used as a contrast agent for magnetic resonance imaging. More importantly, the reactive oxygen species (ROS) generated by RB and NO molecules released from SNO, which are simultaneously triggered by US, can react with each other to yield highly reactive peroxynitrite (ONOO-) ions for effective tumor inhibition both in vitro and in vivo. Furthermore, the nanoplatform demonstrates good hemocompatibility and histocompatibility. This study opens a new strategy for the full utilization of US and intelligent design avenues for high-performance cancer treatment.

Two-dimensional nanovermiculite and polycaprolactone electrospun fibers composite scaffolds promoting diabetic wound healing.

BACKGROUND: Promoting diabetic wound healing is still a challenge, and angiogenesis is believed to be essential for diabetic wound healing. Vermiculite is a natural clay material that is very easy to obtain and exhibits excellent properties of releasing bioactive ions, buffering pH, adsorption, and heat insulation. However, there are still many unsolved difficulties in obtaining two-dimensional vermiculite and using it in the biomedical field in a suitable form. RESULTS: In this study, we present a versatile organic-inorganic composite scaffold, which was constructed by embedding two-dimensional vermiculite nanosheets in polycaprolactone electrospun fibers, for enhancing angiogenesis through activation of the HIF-1α signaling pathway and promoting diabetic wound healing both in vitro and in vivo. CONCLUSIONS: Together, the rational-designed polycaprolactone electrospun fibers-based composite scaffolds integrated with two-dimensional vermiculite nanosheets could significantly improve neo-vascularization, re-epithelialization, and collagen formation in the diabetic wound bed, thus promoting diabetic wound healing. This study provides a new strategy for constructing bioactive materials for highly efficient diabetic wound healing.

Predicting Distant Metastasis in Young-Onset Colorectal Cancer After Surgery: A Retrospective Study.

Background: Although overall colorectal cancer (CRC) cases have been declining worldwide, there has been an increase in the incidence of the CRC among individuals younger than 50 years old, which is associated with distant metastasis (DM) and poor prognosis. Methods: Young-onset CRC patients' postoperative data were collected from the Surveillance, Epidemiology, and End Results (SEER) database between January 2010 and December 2015. Data from the SEER database were divided into early stage and advanced stage according to whether chemoradiotherapy was recommended in the guidelines. Independent risk factors for DM were explored by using univariate and multivariate logistic regression separately. A predictive model was established and presented as nomogram in the training set of advanced stage. The model was internally verified in testing set and externally validated in a cohort of 145 patients from Zhongnan Hospital of Wuhan University. The accuracy, reliability, and clinical application value were assessed using the receiver operating characteristic curve (ROC), the area under the curve (AUC), calibration curve, and decision curve analysis (DCA), respectively. Different risk subgroups of DM were classified according to the scores of the nomogram in the training set of advanced stage. Results: A total of 5,584 patients were eligible and enrolled in our study in which 1,277 were in early stage and 4,307 in advanced stage. Preoperative CEA positive was found to be an independent predictor of DM in early stage. Multivariate logistic regression analysis showed that tumor size, degree of differentiation, T stage, N stage, preoperative CEA, and whether radiation or chemotherapy performed were independent risk factors for DM (all, p < 0.05) in advanced stage. Great accuracies were achieved in our nomogram with AUC of 0.801 in training set, 0.811 in testing set, and 0.791 in the validation cohort, respectively. Calibration curves and DCA in internal validation and external validation both showed good stability and clinical utility values. Conclusions: Preoperative CEA positive was a significant predictor of DM for young-onset CRC patients. A novel nomogram containing clinical and pathological features was established for predicting DM of advanced CRC in patients younger than 50 years old. This tool may serve as an early alert for clinicians to DM and make better clinical treatment regimens.

Gadolinium-doped hollow silica nanospheres loaded with curcumin for magnetic resonance imaging-guided synergistic cancer sonodynamic-chemotherapy.

Curcumin is a kind of anti-cancer chemotherapeutic drug and has been demonstrated to be able to produce reactive oxygen species (ROS) under the stimuli of ultrasound (US). Herein, gadolinium-doped hollow mesoporous silica nanospheres (Gd-HMSNs) loaded with curcumin (Cur) and conjugated with carboxymethyl dextran (CMD) have been facilely fabricated and applied for magnetic resonance imaging (MRI)-guided synergistic cancer sonodynamic-chemotherapy. The as-prepared multifunctional theranostic nanoplatform (Cur@Gd-HMSNs-CMD) shows high drug loading capacity, satisfactory biocompatibility, pH-responsive degradation, and US-triggered drug release. Due to the release of Gd3+ ions or oligomers during degradation, the nanoplatform Cur@Gd-HMSNs-CMD could serve as an effective contrast agent for T1-weighted MRI to guide cancer treatment. More significantly, in vivo experiments show that the Cur@Gd-HMSNs-CMD can efficiently inhibit the tumor growth by a high inhibition rate of ~85.6% under US irradiation, mainly resulting from the synergistic effect of sonodynamic-chemotherapy. This innovative "two-in-one" theranostic nanoplatform using a single drug provides a new strategy for developing "all-in-one" nanomaterials for combined cancer treatment.

Functionalized g-C3N4 nanosheets for potential use in magnetic resonance imaging-guided sonodynamic and nitric oxide combination therapy.

The oxygen consumption-induced hypoxia and the high concentration of glutathione in tumor microenvironment limit the treatment outcomes of sonodynamic therapy (SDT). SDT needs to be combined with other treatment modalities to achieve the desired therapeutic efficiency. In this study, an oxidized g-C3N4 (OCN) nanosheet-based theranostic nanoplatform is developed for sonodynamic and nitric oxide (NO) combination therapy of cancer. The OCN nanosheets are successively modified with amino-terminated 6-armed polyethylene glycol, chlorin e6, and Gd3+ ions, and then the as-prepared OCN-PEG-(Ce6-Gd3+) nanosheets are loaded with the NO donor N,N'-di-sec-butyl-N,N'-dinitroso-1,4-phenylenediamine (BNN6). Upon ultrasound (US) irradiation, the OCN-PEG-(Ce6-Gd3+)/BNN6 nanocomposite can induce the generation of reactive oxygen species (ROS) and simultaneously release NO molecules to effectively kill the cancer cells, thereby significantly suppressing the tumor growth. Moreover, a good in vivo T1-weighted magnetic resonance imaging (MRI) contrast effect is achieved after intravenous injection of OCN-PEG-(Ce6-Gd3+)/BNN6 due to remarkably enhanced contrast performance of the nanocomposite. Therefore, the OCN-PEG-(Ce6-Gd3+)/BNN6 formulation can serve as a promising theranostic agent for MRI-guided sonodynamic-NO combination therapy.

A New Green Titania with Enhanced NIR Absorption for Mitochondria-Targeted Cancer Therapy.

A new kind of green titania (G-TiO2-x ) with obvious green color was facilely synthesized from black titania (B-TiO2-x ) through subsequently strong ultrasonication. Comparatively, this stable G-TiO2-x shows much enhanced near infrared (NIR) absorption, especially around 920 nm, which can be ascribed to the obvious change of TiO2-x lattice order owing to the effect of ultrasonication. This feature enables G-TiO2-x to be stimulated with 980 nm laser in the combined photodynamic therapy (PDT) and photothermal therapy (PTT), which is greatly beneficial for improving tissue penetration depth. Furthermore, since mitochondria are preferred subcellular organelles for PDT/PTT, G-TiO2-x was further designed to conjugate with triphenylphosphonium (TPP) ligand for mitochondria-targeted PDT/PTT to obtain precise cancer treatment. Attributing to the high mitochondria-targeting efficiency and simultaneously synergistic PDT/PTT, high phototherapeutic efficacy and safety with a much lower laser power density (980 nm, 0.72 W cm-2) and low materials dosage were achieved both in vitro and in vivo. In addition, negligible toxicity was found, indicating high biocompatibility. This novel G-TiO2-x could provide new strategies for future precise minimal/non-invasive tumor treatment.

Black titania-based theranostic nanoplatform for single NIR laser induced dual-modal imaging-guided PTT/PDT.

Substantially different from traditional combinatorial-treatment of photothermal therapy (PTT) and photodynamic therapy (PDT) by using multi-component nanocomposite under excitation of separate wavelength, a novel single near infrared (NIR) laser-induced multifunctional theranostic nanoplatform has been rationally and successfully constructed by a single component black titania (B-TiO2-x) for effective imaging-guided cancer therapy for the first time. This multifunctional PEGylated B-TiO2-x shows high dispersity/stability in aqueous solution, excellent hemo/histocompatibility and broad absorption ranging from NIR to ultraviolet (UV). Both in vitro and in vivo results well demonstrated that such a novel multifunctional theranostic nanoplaform could achieve high therapeutic efficacy of simultaneous and synergistic PTT/PDT under the guidance of infrared thermal/photoacoustic (PA) dual-modal imaging, which was triggered by a single NIR laser. This research circumvents the conventional obstacles of using multi-component nanocomposites, UV light and high laser power density. Furthermore, negligible side effects to blood and main tissues could be found in 3 months' investigation, facilitating its potential biomedical application.

CO2 bubbling-based 'Nanobomb' System for Targetedly Suppressing Panc-1 Pancreatic Tumor via Low Intensity Ultrasound-activated Inertial Cavitation.

Noninvasive and targeted physical treatment is still desirable especially for those cancerous patients. Herein, we develop a new physical treatment protocol by employing CO2 bubbling-based 'nanobomb' system consisting of low-intensity ultrasound (1.0 W/cm(2)) and a well-constructed pH/temperature dual-responsive CO2 release system. Depending on the temperature elevation caused by exogenous low-intensity therapeutic ultrasound irradiation and the low pH caused by the endogenous acidic-environment around/within tumor, dual-responsive CO2 release system can quickly release CO2 bubbles, and afterwards, the generated CO2 bubbles waves will timely explode before dissolution due to triggering by therapeutic ultrasound waves. Related bio-effects (e.g., cavitation, mechanical, shock waves, etc) caused by CO2 bubbles' explosion effectively induce instant necrosis of panc-1 cells and blood vessel destruction within panc-1 tumor, and consequently inhibit the growth of panc-1 solid tumor, simultaneously minimizing the side effects to normal organs. This new physiotherapy employing CO2 bubbling-based 'nanobomb' system promises significant potentials in targetedly suppressing tumors, especially for those highly deadly cancers.

A facile synthesis of versatile Cu2-xS nanoprobe for enhanced MRI and infrared thermal/photoacoustic multimodal imaging.

A novel type of intelligent nanoprobe by using single component of Cu2-xS for multimodal imaging has been facilely and rapidly synthesized in scale via thermal decomposition followed by biomimetic phospholipid modification, which endows them with uniform and small nanoparticle size (ca.15 nm), well phosphate buffer saline (PBS) dispersity, high stability, and excellent biocompatibility. The as-synthesized Cu2-xS nanoprobes (Cu2-xS NPs) are capable of providing contrast enhancement for T1-weighted magnetic resonance imaging (MRI), as demonstrated by the both in vitro and in vivo imaging investigations for the first time. In addition, due to their strong near infrared (NIR) optical absorption, they can also serve as a candidate contrast agent for enhanced infrared thermal/photoacoustic imaging, to meet the shortfalls of MRI. Hence, complementary and potentially more comprehensive information can be acquired for the early detection and accurate diagnosis of cancer. Furthermore, negligible systematic side effects to the blood and tissue were observed in a relatively long period of 3 months. The distinctive multimodal imaging capability with excellent hemo/histocompatibility of the Cu2-xS NPs could open up a new molecular imaging possibility for detecting and diagnosing cancer or other diseases in the future.

Ultrasmall Cu2-x S Nanodots for Highly Efficient Photoacoustic Imaging-Guided Photothermal Therapy.

Monodisperse, ultrasmall (<5 nm) Cu(2-x)S nanodots (u-Cu(2-x)S NDs) with significantly strong near-infrared absorption and conversion are successfully demonstrated for effective deep-tissue photoacoustic imaging-guided photothermal therapy both in vitro and in vivo. Owing to ultrasmall nanoparticle size and high water dispersibility as well as long stability, such nanodots possess a prolonged circulation in blood and good passive accumulation within tumors through the enhanced permeability and retention effect. These u-Cu(2-x)S NDs have negligible side effects to both blood and normal tissues according to in vivo toxicity evaluations for up to 3 months, showing excellent hemo/histocompatibility. Furthermore, these u-Cu(2-x)S NDs can be thoroughly cleared through feces and urine within 5 days, showing high biosafety for further potential clinical translation. This novel photoacoustic imaging-guided photothermal therapy based on u-Cu(2-x)S NDs composed of a single component shows great prospects as a multifunctional nanoplatform with integration and multifunction for cancer diagnosis and therapy.

A continuous tri-phase transition effect for HIFU-mediated intravenous drug delivery.

Aiming at substantially enhanced efficacy and biosafety of clinical HIFU therapy, a natural solid medium, L-menthol (LM), characteristic of mild and controllable "solid-liquid-gas" (SLG) tri-phase transition, was adopted, instead of those conventional explosive liquid-gas (LG) bi-phase transitional media, in constructing a multifunctional theranostic system. Owing to the continuous and controllable characteristics of SLG tri-phase transition, such a novel tri-phase transition-based theranostic system has been demonstrated of the repeatedly enhanced HIFU efficacy ex vivo and in vivo under once intravenous injection and the significantly improved treatment precision, controllability and biosafety when comparing to the traditional bi-phase transition medium, perfluorohexane (PFH), thus promising great application potential in clinical HIFU treatment. Moreover, this theranostic system has been demonstrated a long blood-circulation lifetime and continuous accumulation in tumor in 24 h, which is very beneficial for the enhanced tumor ablation in vivo along with SLG tri-phase transition. More importantly, after loading multiple model drugs and real drug, such a theranostic system presents a HIFU-mediated temperature-responsive drug release property, and depending on the versatile miscibility of LM, co-loadings with hydrophobic and hydrophilic drugs are also achieved, which provides the possibility of synergistic treatment combining HIFU therapy and chemotherapy.