Iodinated cyanine dye-based nanosystem for synergistic phototherapy and hypoxia-activated bioreductive therapy.

Photodynamic therapy (PDT) has been applied in cancer treatment by utilizing reactive oxygen species (ROS) to kill cancer cells. However, the effectiveness of PDT is greatly reduced due to local hypoxia. Hypoxic activated chemotherapy combined with PDT is expected to be a novel strategy to enhance anti-cancer therapy. Herein, a novel liposome (LCT) incorporated with photosensitizer (PS) and bioreductive prodrugs was developed for PDT-activated chemotherapy. In the design, CyI, an iodinated cyanine dye, which could simultaneously generate enhanced ROS and heat than other commonly used cyanine dyes, was loaded into the lipid bilayer; while tirapazamine (TPZ), a hypoxia-activated prodrug was encapsulated in the hydrophilic nucleus. Upon appropriate near-infrared (NIR) irradiation, CyI could simultaneously produce ROS and heat for synergistic PDT and photothermal therapy (PTT), as well as provide fluorescence signals for precise real-time imaging. Meanwhile, the continuous consumption of oxygen would result in a hypoxia microenvironment, further activating TPZ free radicals for chemotherapy, which could induce DNA double-strand breakage and chromosome aberration. Moreover, the prepared LCT could stimulate acute immune response through PDT activation, leading to synergistic PDT/PTT/chemo/immunotherapy to kill cancer cells and reduce tumor metastasis. Both in vitro and in vivo results demonstrated improved anticancer efficacy of LCT compared with traditional PDT or chemotherapy. It is expected that these iodinated cyanine dyes-based liposomes will provide a powerful and versatile theranostic strategy for tumor target phototherapy and PDT-induced chemotherapy.

Assembly of gold nanorods with L-cysteine reduced graphene oxide for highly efficient NIR-triggered photothermal therapy.

Near-infrared (NIR) photothermal therapy is an effective partner to the chemotherapy of tumors with the merits of high therapeutic ability and slight side effect on normal tissues. Herein, we synthesized gold nanorods and assembled them with L-cysteine reduced graphene oxide (AuNR@Lcyst-rGO) for efficient photothermal therapy. The high therapeutic efficacy of AuNR@Lcyst-rGO can be due to the high photothermal effect of gold nanorods and reduced graphene oxide, and the synergistic effect of them. The nontoxicity of L-cysteine also guarantees the comfortable biocompatibility of reduced graphene oxide, which is essential for the photothermal absorber used in human tissue. The results demonstrate that assembly of gold nanorods with reduced graphene oxide (AuNR@Lcyst-rGO) is a promising photothermal agent with high efficient NIR-triggered photothermal therapy efficiency, excellent stability, superior biocompatibility.

Treatment of rheumatoid arthritis by phototherapy: advances and perspectives.

Rheumatoid arthritis (RA) is an inflammatory disease that is prevalent worldwide and seriously threatens human health. Though traditional drug therapy can alleviate RA symptoms and slow progression, high dosage and frequent administration would cause unfavorable side effects. Phototherapy including photodynamic therapy (PDT) and photothermal therapy (PTT) has demonstrated distinctive potential in RA treatment. Under light irradiation, phototherapy can convert light into heat, or generate ROS, to promote necrosis or apoptosis of RA inflammatory cells, thus reducing the concentration of related inflammatory factors and relieving the symptoms of RA. In this review, we will summarize the development in the application of phototherapy in the treatment of rheumatoid arthritis.

The Median Effective Dose of One Intravenous Bolus of Oxycodone for Postoperative Analgesia After Myomectomy and Hysterectomy With Local Ropivacaine Wound Infiltration: An Up-Down Dose-Finding Study.

BACKGROUND: Oxycodone has been shown to be an effective analgesic for early postoperative analgesia, especially for abdominal operations associated with severe visceral pain. However, the dose needed varies depending on the operation and application of multimodal analgesia, such as local ropivacaine wound infiltration. Therefore, we conducted this study to estimate the median effective dose (ED50) of oxycodone that provides analgesia for hysterectomy and myomectomy with local ropivacaine wound infiltration. METHODS: In this dose-finding study, the ED50 of oxycodone for postoperative analgesia was estimated separately for laparoscopic hysterectomy, transabdominal hysterectomy, laparoscopic myomectomy, and transabdominal myomectomy. We used the sequential allocation designed by Dixon. Trials were conducted simultaneously in the 4 surgical type groups. A predefined dose of oxycodone was injected 30 minutes before the end of the operation with an initial dose of 0.1 mg/kg. A series of trials were performed following the rule of a relative 10% increase in dose after inadequate analgesia and a relative 10% decrease in dose after adequate analgesia. The study was conducted until the collection of 7 crossover points was achieved. Local ropivacaine wound infiltration was administered during abdominal stitching. The mean blood pressure (MBP) and heart rate (HR) were analyzed to assess the hemodynamic changes associated with oxycodone administration. RESULTS: A total of 113 patients were included in the estimation of ED50: 28 each in the laparoscopic hysterectomy group and transabdominal myomectomy group, 27 in the transabdominal hysterectomy group, and 30 in the laparoscopic myomectomy group. The estimated oxycodone ED50 (95% confidence interval [CI]) after laparoscopic hysterectomy, transabdominal hysterectomy, laparoscopic myomectomy, and transabdominal myomectomy was 0.060 mg/kg (0.053-0.068), 0.079 mg/kg (0.072-0.086), 0.060 mg/kg (0.051-0.071), and 0.092 mg/kg (0.086-0.098), respectively, for postoperative analgesia with local ropivacaine wound infiltration. The ED50 of oxycodone was different between laparoscopic surgeries and transabdominal surgeries (P < .001). The MBP and HR before and after oxycodone injection were different, regardless of surgical type. CONCLUSIONS: The oxycodone ED50 for postoperative analgesia was lower for laparoscopic hysterectomy (0.060 mg/kg) and laparoscopic myomectomy (0.060 mg/kg) than for transabdominal hysterectomy (0.079 mg/kg) and transabdominal myomectomy (0.092 mg/kg) when combined with local ropivacaine wound infiltration. A single intravenous injection of oxycodone is associated with an acceptable decrease in MBP and HR within a short time.