An Improved Multitask Learning Model with Matching Network and Its Application in Traditional Chinese Medicine Syndrome Recommendation.

Multitask learning (MTL) is an open and challenging problem in various real-world applications, such as recommendation systems, natural language processing, and computer vision. The typical way of conducting multitask learning is establishing some global parameter sharing mechanism among all tasks or assigning each task an individual set of parameters with cross-connections between tasks. However, for most existing approaches, the raw features are abstracted step by step, semantic information is mined from input space, and matching relation features are not introduced into the model. To solve the above problems, we propose a novel MMOE-match network to model the matches between medical cases and syndrome elements and introduce the recommendation algorithm into traditional Chinese medicine (TCM) study. Accurate medical record recommendation is significant for intelligent medical treatment. Ranking algorithms can be introduced in multi-TCM scenarios, such as syndrome element recommendation, symptom recommendation, and drug prescription recommendation. The recommendation system includes two main stages: recalling and ranking. The core of recalling and ranking is a two-tower matching network and multitask learning. MMOE-match combines the advantages of recalling and ranking model to design a new network. Furtherly, we try to take the matching network output as the input of multitask learning and compare the matching features designed by the manual. The data show that our model can bring significant positive benefits.

Silver Mesoporous Silica Nanoparticles: Fabrication to Combination Therapies for Cancer and Infection.

The integration of silver nanoparticles (Ag NPs) with mesoporous silica nanoparticles (MSNs) protects the former from aggregation and promotes the controlled release of silver ions, resulting in therapeutic significance on cancer and infection. The unique size, shape, pore structure and silver distribution of silver mesoporous silica nanoparticles (Ag-MSNs) embellish them with the potential to perform combined imaging and therapeutic actions via modulating optical and drug release properties. Here, we comprehensively review the recent progress in the fabrication and application of Ag-MSNs for combination therapies for cancer and infection. We first elaborate on the fabrication of star-shaped structure, core-shell structure, and Janus structure Ag-MSNs. We then highlight Ag-MSNs as a multifunctional nanoplatform to surface-enhanced Raman scattering-based detection, non-photo-based cancer theranostics and photo-based cancer theranostics. In addition, we detail Ag-MSNs for combined antibacterial therapy via drug delivery and phototherapy. Overall, we summarize the challenges and future perspectives of Ag-MSNs that make them promising for diagnosis and therapy of cancer and infection.

Nanosilver-Decorated Biodegradable Mesoporous Organosilica Nanoparticles for GSH-Responsive Gentamicin Release and Synergistic Treatment of Antibiotic-Resistant Bacteria.

PURPOSE: Antibiotic-resistant bacteria are pathogens that have emerged as a serious public health risk. Thus, there is an urgent need to develop a new generation of anti-bacterial materials to kill antibiotic-resistant bacteria. METHODS: Nanosilver-decorated mesoporous organosilica nanoparticles (Ag-MONs) were fabricated for co-delivery of gentamicin (GEN) and nanosilver. After investigating the glutathione (GSH)-responsive matrix degradation and controlled release of both GEN and silver ions, the anti-bacterial activities of Ag-MONs@GEN were systematically determined against several antibiotic-susceptible and antibiotic-resistant bacteria including Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis. Furthermore, the cytotoxic profiles of Ag-MONs@GEN were evaluated. RESULTS: The GEN-loaded nanoplatform (Ag-MONs@GEN) showed glutathione-responsive matrix degradation, resulting in the simultaneous controlled release of GEN and silver ions. Ag-MONs@GEN exhibited excellent anti-bacterial activities than Ag-MONs and GEN alone via inducing ROS generation, especially enhancing synergetic effects against four antibiotic-resistant bacteria including Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis. Moreover, the IC50 values of Ag-MONs@GEN in L929 and HUVECs cells were 313.6 ± 15.9 and 295.7 ± 12.3 µg/mL, respectively, which were much higher than their corresponding minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values. CONCLUSION: Our study advanced the development of Ag-MONs@GEN for the synergistic and safe treatment of antibiotic-resistant bacteria.

MBene as a Theranostic Nanoplatform for Photocontrolled Intratumoral Retention and Drug Release.

Tumor-targeted drug delivery by nanomaterials is important to improve tumor therapy efficacy and reduce toxic side effects, but its efficiency is quite limited. In this work, a new type of MBene, zirconium boride nanosheet (ZBN), as a versatile nanoplatform to realize near-infrared (NIR)-controlled intratumoral retention and drug release is developed. ZBN exhibits high NIR-photothermal conversion efficiency (76.8%), surface modification with hyaluronic acid (HA) by polyol-borate esterfication endows ZBN-HA with good dispersion, and the photopyrolysis of borate ester causes HA detachment and ZBN aggregation, enabling NIR-controlled intratumoral retention to achieve high intratumoral accumulation. By virtue of surface borate esterfication, polyol chemotherapeutic drug (doxorubicin, DOX), and NO prodrug (ß-galactosyl-diazeniumdiolate, Gal-NO) can be efficiently and stably conjugated on the surface of ZBN-HA (1.21 g DOX or 0.57 g Gal-NO per gram ZBN) without visible drug leakage, and the photopyrolysis of borate ester enables NIR-controlled drug release with high responsiveness and controllability. Combined chemothermal/gasothermal therapies based on ZBN-HA/DOX and ZBN-HA/NO nanomedicines eradicate primary tumors and interdict tumor metastasis by changing the tumor microenvironment and killing cancer cells in primary tumors. The developed NIR-photothermal MBene is confirmed as a versatile nanoplatform capable of high-efficacy tumor-targeted drug delivery and controlled drug release.

Photocatalysis-mediated drug-free sustainable cancer therapy using nanocatalyst.

Drug therapy unavoidably brings toxic side effects and drug content-limited therapeutic efficacy although many nanocarriers have been developed to improve them to a certain extent. In this work, a concept of drug-free therapeutics is proposed and defined as a therapeutic methodology without the use of traditional toxic drugs, without the consumption of therapeutic agents during treatment but with the inexhaustible therapeutic capability to maximize the benefit of treatment, and a Z-scheme SnS1.68-WO2.41 nanocatalyst is developed to achieve near infrared (NIR)-photocatalytic generation of oxidative holes and hydrogen molecules for realizing combined hole/hydrogen therapy by the drug-free therapeutic strategy. Without the need of any drug and other therapeutic agent assistance, the nanocatalyst oxidizes/consumes intratumoral over-expressed glutathione (GSH) by holes and simultaneously generates hydrogen molecules in a lasting and controllable way under NIR irradiation. Mechanistically, generated hydrogen molecules and GSH consumption inhibit cancer cell energy and destroy intratumoral redox balance, respectively, to synergistically damage DNA and induce tumor cell apoptosis. High efficacy and biosafety of combined hole/hydrogen therapy of tumors are achieved by the nanocatalyst. The proposed catalysis-based drug-free therapeutic strategy breaks a pathway to realize high efficacy and low toxicity of cancer treatment.

Janus Gold Triangle-Mesoporous Silica Nanoplatforms for Hypoxia-Activated Radio-Chemo-Photothermal Therapy of Liver Cancer.

Radiation dosage constraints and hypoxia-associated resistance lead to the failure of radiotherapy (RT), especially in hypoxic liver cancer. Therefore, the intricate use of combined strategies for potentiating and complementing RT is especially important. In this work, we fabricated multifunctional Janus-structured gold triangle-mesoporous silica nanoparticles (NPs) as multifunctional platforms to deliver the hypoxia-activated prodrug tirapazamine (TPZ) for extrinsic radiosensitization, local photothermal therapy, and hypoxia-specific chemotherapy. The subsequent conjugation of folic acid-linked poly(ethylene glycol) provided the Janus nanoplatforms with liver cancer targeting and minimized opsonization properties. In vitro and in vivo experiments revealed the combined radiosensitive and photothermal antitumor effects of the Janus nanoplatforms. Importantly, the TPZ-loaded Janus nanoplatforms exhibited pH-responsive release behavior, which effectively improved the cellular internalization and therapeutic efficiency in hypoxic rather than normoxic liver cancer cells. Hypoxia-specific chemotherapy supplemented the ineffectiveness of radio-photothermal therapy in hypoxic tumor tissues, resulting in remarkable tumor growth inhibition without systematic toxicity. Therefore, our Janus nanoplatforms integrated radio-chemo-photothermal therapy in a hypoxia-activated manner, providing an efficient and safe strategy for treating liver cancer.

Green synthesis of carrier-free curcumin nanodrugs for light-activated breast cancer photodynamic therapy.

Photodynamic therapy (PDT) is a promising procedure for breast cancer therapy. Curcumin (Cur), a hydrophobic polyphenol derived from the spice turmeric, has been considered as a potential photosensitizer for PDT with evoked immune response, excellent safety, and low cost. However, the translation of curcumin in clinical cancer therapy suffers from an insufficient therapeutic dose in tumor tissues due to its poor solubility and low bioavailability. In this study, carrier-free curcumin nanodrugs (Cur NDs) were prepared without using any toxic solvents through a facile and green reprecipitation method. Cur NDs exhibited distinct optical properties, light-sensitive drug release behavior, resulting in increased reactive oxygen species (ROS) generation and PDT efficacy on breast cancer cells compared with free Cur. Furthermore, cell apoptosis during Cur-based PDT was concomitant with the activation of the ROS-mediated JNK/caspase-3 signaling pathway. Overall, our carrier-free Cur nanodrugs may be promising candidates for facilitating the efficacy and safety of PDT against breast cancer.

Berberine-loaded Janus nanocarriers for magnetic field-enhanced therapy against hepatocellular carcinoma.

Berberine, an bioactive isoquinolin alkaloid from traditional Chinese herbs, is considered to be a promising agent based on its remarkable activity against hepatocellular carcinoma. However, the clinical application of this nature compound had been hampered owing to its properties such as poor aqueous solubility, low gastrointestinal absorption, and reduced bioavailability. Therefore, we developed Janus magnetic mesoporous silica nanoparticles (Fe3 O4 -mSiO2 NPs) consisting of a Fe3 O4 head for magnetic targeting and a mesoporous SiO2 body for berberine delivery. A pH-sensitive group was introduced on the surface of mesoporous silica for berberine loading to develop a tumor microenvironment-responsive nanocarrier, which exhibited uniform morphology, good superparamagnetic properties, high drug-loading amounts, superior endocytic ability, and low cytotoxicity. Berberine-loaded Fe3 O4 -mSiO2 NPs exerted extraordinarily high specificity for hepatocellular carcinoma cells, which was due to the pH-responsive berberine release, as well as higher endocytosis capacity in hepatocellular carcinoma cells rather than normal liver cells. More importantly, an external magnetic field could significantly improve antitumor activity of Ber-loaded Fe3 O4 -mSiO2 NPs through enhancing berberine internalization. Taken together, our results suggest that Janus nanocarriers driven by the magnetic field may provide an effective and safe way to facilitate clinical use of berberine against hepatocellular carcinoma.