Photothermal-accelerated urease-powered human serum albumin nanomotor for rapid and efficient photothermal and photodynamic cancer combination therapy.

Nanomotors, as a new type of micro-device, show good performance in terms of rapid transportation and deep penetration through their autonomous motion. However, their ability to efficiently break physiological barriers still remains a great challenge. Herein, we first developed a thermal-accelerated urease driven human serum albumin (HSA) nanomotor based on photothermal intervention (PTI) to achieve chemotherapy drugfree-phototherapy. The HANM@FI (HSA-AuNR@FA@Ur@ICG) is composed of a main body of biocompatible HSA, modified by gold nanorods (AuNR) and loaded with functional molecules of folic acid (FA) and indocyanine green (ICG). It promotes its own motion by breaking down urea to produce carbon dioxide and ammonia. In particular, the nanomotor is conveniently operated via near-infrared combined photothermal therapy (PTT)/ photodynamic therapy (PDT) to achieve an accelerated De value from 0.73 µm2s-1 to 1.01µm2s-1, and ideal tumor ablation at the same time. In contrast to customary urease-driven nanodrug-stacked engine, this HANM@FI has both targeting and imaging-guided capabilities, and finally achieves superior anti-tumor effects without chemotherapy drugs, through a "two-in-one" (motor mobility plus unique phototherapy in chemotherapy-drugfree phototherapy) strategy. This PTI effect with urease-driven nanomotors may offer further possibilities for future clinical applications of nanomedicines by enabling deep penetration and a subsequent chemotherapy-drugfree combination therapy strategy.

Laser stimulating ST36 with optical fiber induce blood component changes in mice: a Raman spectroscopy study.

ST36 is a commonly-used acupoint in traditional Chinese medicine (TCM) for treatment of inflammations, pains and gastrointestinal disturbs. For decades, the low power laser acupuncture has been widely applied as an alternative therapy to traditional metal needle acupuncture and achieved relatively fine therapeutic effect for ST36-related symptoms with reduction of uncomfortableness and infection risks. However its disadvantages of low penetrativity and lack of manipulation skills limit its potential performance. An optical fiber laser acupuncture introduced by the previous study combines traditional needling acupuncture and the laser stimulation together, making a stronger therapeutic effect and showing a potential value in clinical application. To evaluate its acupunctural effect on blood, mice are taken as experimental model and Raman spectroscopic technique is used to analysis the changes of blood components after stimulating on ST36. The results show that both the traditional needling acupuncture and optical fiber acupuncture could lead to some spectral changes of blood in mice. This study explores the optical fiber acupuncture's effect on blood in mice using Raman spectroscopy technique for mechanism of acupuncture therapy.

LED Phototherapy with Gelatin Sponge Promotes Wound Healing in Mice.

Tiny but highly efficient, a light-emitting diode (LED) can power a therapy device, such as a phototherapy device, and, at the same time, decrease the device's size requirements. In this study, a LED phototherapy device was designed to investigate the possible impact on wound healing using a mouse model and a cell line exposed to red and blue light. To enhance wound phototherapy, a gelatin sponge was fabricated. Results showed that the red and blue lights promoted cell growth and wound healing, while the blue light with a gelatin sponge protected the wound from infection in the early stages of wound healing. The LED phototherapy device combined with the gelatin sponge, therefore, has potential significance in clinical application for wound healing.

A Multimodal System with Synergistic Effects of Magneto-Mechanical, Photothermal, Photodynamic and Chemo Therapies of Cancer in Graphene-Quantum Dot-Coated Hollow Magnetic Nanospheres.

In this study, a multimodal therapeutic system was shown to be much more lethal in cancer cell killing compared to a single means of nano therapy, be it photothermal or photodynamic. Hollow magnetic nanospheres (HMNSs) were designed and synthesized for the synergistic effects of both magneto-mechanical and photothermal cancer therapy. By these combined stimuli, the cancer cells were structurally and physically destroyed with the morphological characteristics distinctively different from those by other therapeutics. HMNSs were also coated with the silica shells and conjugated with carboxylated graphene quantum dots (GQDs) as a core-shell composite: HMNS/SiO2/GQDs. The composite was further loaded with an anticancer drug doxorubicin (DOX) and stabilized with liposomes. The multimodal system was able to kill cancer cells with four different therapeutic mechanisms in a synergetic and multilateral fashion, namely, the magnetic field-mediated mechanical stimulation, photothermal damage, photodynamic toxicity, and chemotherapy. The unique nanocomposites with combined mechanical, chemo, and physical effects will provide an alternative strategy for highly improved cancer therapy efficiency.

Change in refractive index of muscle tissue during laser-induced interstitial thermotherapy.

This paper presents a long-period fiber-grating (LPG) based Michelson interferometric refractometry to monitor the change in refractive index of porcine muscle during laser-induced interstitial thermotherapy (LITT). As the wavelength of RI interferometer alters with the change in refractive index around the probe, the LPG based refractometry is combined with LITT system to measure the change in refractive index of porcine muscle when irradiated by laser. The experimental results show the denaturation of tissue alters the refractive index significantly and the LPG sensor can be applied to monitor the tissue state during the LITT.

Examining the interactome of huperzine A by magnetic biopanning.

Huperzine A is a bioactive compound derived from traditional Chinese medicine plant Qian Ceng Ta (Huperzia serrata), and was found to have multiple neuroprotective effects. In addition to being a potent acetylcholinesterase inhibitor, it was thought to act through other mechanisms such as antioxidation, antiapoptosis, etc. However, the molecular targets involved with these mechanisms were not identified. In this study, we attempted to exam the interactome of Huperzine A using a cDNA phage display library and also mammalian brain tissue extracts. The drugs were chemically linked on the surface of magnetic particles and the interactive phages or proteins were collected and analyzed. Among the various cDNA expressing phages selected, one was identified to encode the mitochondria NADH dehydrogenase subunit 1. Specific bindings between the drug and the target phages and target proteins were confirmed. Another enriched phage clone was identified as mitochondria ATP synthase, which was also panned out from the proteome of mouse brain tissue lysate. These data indicated the possible involvement of mitochondrial respiratory chain matrix enzymes in Huperzine A's pharmacological effects. Such involvement had been suggested by previous studies based on enzyme activity changes. Our data supported the new mechanism. Overall we demonstrated the feasibility of using magnetic biopanning as a simple and viable method for investigating the complex molecular mechanisms of bioactive molecules.

Electrocardiographic and biochemical evidence for the cardioprotective effect of antioxidants in acute doxorubicin-induced cardiotoxicity in the beagle dogs.

Doxorubicin (DOX) is a potent antitumor agent, but the cardiotoxicity mediated by the formation of reactive oxygen species limit its clinical use. The present study aims to explore electrocardiographic and biochemical evidence for the cardioprotective effect of two antioxidants, Lycium barbarum polysaccharides (LBP, the main antioxidant in Lycium barbarum) and edaravone (a potent free radical scavenger, EDA) against DOX-induced acute cardiotoxicity in beagle dogs. In this study, male beagle dogs received daily treatment of either LBP (20 mg/kg, per os (p.o.)) or EDA (2 mg/kg, intravenously (i.v.)) for 7 d and then followed by an intravenous injection of DOX (1.5 mg/kg). DOX (15 mg/kg) significantly induced acute cardiotoxicity in dogs characterized by conduction abnormalities (including decreased heart rate, ST segment elevation, QT intervals prolongation, inverted T wave, arrhythmia, and myocardial ischemia) and increased serum creatine kinase (CK) and aspartate aminotransferase (AST). Pretreatment with LBP or EDA effectively alleviated both DOX-associated conduction abnormalities and increased serum CK and AST. Moreover, physiological and serum biochemical evidences demonstrated that EDA is more effective than LBP in alleviating these abnormalities produced by DOX in heart. All these results confirm and extend previous observations in rats concerning the effectiveness of LBP or EDA against DOX-induced cardiomyopathy.

Magnetic screening of the potential targeted protein of salvianolic acid B using T7 phage display library.

Salvianolic acid B is one of the effective components from the Chinese traditional drug Salvia miltiorrhiza (Danshen), which is widely used as a usual clinic drug for atherosclerosis-related disorder patients in China. But the targeting protein of salvianolic acid B is still not known. The possible targeting proteins of salvianolic acid B were explored by high throughput screening in this paper. Attached to the magnetic nanoparticles, salvianolic acid B was used for screening the high-affinity protein from the displaying cDNA peptide library phage. After biopanning, the selected protein or peptide sequences were used to explore the whole proteins containing the selected sequences in the National Center for Biotechnology Information website using blast. One of the selected phages was carried out by affinity analysis with salvianolic acid B using capillary electrophoresis (CE). The CE results indicated that the protein or peptide on the surface of the selected phages could bind the drug salvianolic acid B. The results are helpful to preliminarily explain the pharmacology of salvianolic acid B.

Angelica sinensis: a novel adjunct to prevent doxorubicin-induced chronic cardiotoxicity.

Doxorubicin is an anthracycline antibiotic agent used in the treatment of a variety of solid and haematopoietic tumours, but its use is limited by formation of metabolites that induce acute and chronic cardiac toxicities. Angelica sinensis has been widely used to treat cardiovascular and cerebrovascular diseases in China. In the present study, we used an in vivo mouse model to explore whether A. sinensis could protect against doxorubicin-induced chronic cardiotoxicity. Male ICR mice were treated with distilled water or water extraction of A. sinensis (15 g/kg, orally) daily for 4 weeks, followed by saline or doxorubicin (15 mg/kg, intravenously) treatments weekly. Cardiotoxicity was assessed by electrocardiograph, antioxidant activity in cardiac tissues, serum levels of creatine kinase, aspartate aminotransferase (AST) and histopathological change in cardiac tissues. A cumulative dose of doxorubicin (60 mg/kg) caused animal death and myocardial injury characterized by increased QT interval and decreased heart rate in electrocardiograph, decrease of heart antioxidant activity, increase of serum AST, as well as myocardial lesions. Pre-treatment with A. sinensis significantly reduced mortality and improved heart performance of the doxorubicin-treated mice as evidenced from normalization of antioxidative activity and serum AST, preventing loss of myofibrils as well as improving arrhythmias and conduction abnormalities. Furthermore, the in vitro cytotoxic study showed that A. sinensis did not compromise the antitumour activity of doxorubicin. These results suggested that A. sinensis elicited a typical cardioprotective effect on doxorubicin-related oxidative stress, and could be a novel adjunct in the combination with doxorubicin chemotherapy.