pH-Responsive Micellar Nanoparticles for the Delivery of a Self-Amplifying ROS-Activatable Prodrug.

The objective of this study is to enhance the therapeutic efficacy of the anticancer drug, camptothecin (CPT) via a nanoparticle (NP) formulation using a novel amphiphilic biopolymer. We have designed a dimeric prodrug of CPT with the ability to self-amplify and respond to reactive oxygen species (ROS). For this, we incorporated the intracellular ROS generator cinnamaldehyde into a ROS-cleavable thioacetal (TA) linker to obtain the dimeric prodrug of CPT (DCPT(TA)). For its efficient NP delivery, a pH-responsive block copolymer of acetalated dextran and poly(2-ethyl-2-oxazoline) (AcDex-b-PEOz) was synthesized. The amphiphilic feature of the block copolymer enables its self-assembly into micellar NPs and results in high prodrug loading capacity and a rapid release of the prodrug under acidic conditions. Upon cellular uptake by HeLa cells, DCPT(TA)-loaded micellar NPs induce intracellular ROS generation, resulting in accelerated prodrug activation and enhanced cytotoxicity. These results indicate that this system holds significant potential as an effective prodrug delivery strategy in anticancer treatment.

Water-soluble bright NIR AIEgens with hybrid ROS for wash-free mitochondrial "off-on" imaging and photodynamic therapy.

Several aggregation-induced emission luminogens (AIEgens) with excellent water-solubility and near-infrared emission were designed and synthesized for wash-free "off-on" mitochondrial imaging and photodynamic therapy of HeLa cells. The AIEgen TEPP exhibits both bright near-infrared emission (φF = 17.8%) and high hybrid ROS productivity (including OH˙ and 1O2).

Effects of Radiation on Drug Metabolism: A Review.

BACKGROUND: Radiation is the fourth most prevalent type of pollution following the water, air and noise pollution. It can adversely affect normal bodily functions. Radiation alters the protein and mRNA expression of drugmetabolizing enzymes and drug transporters and the pharmacokinetic characteristics of drugs, thereby affecting drug absorption, distribution, metabolism, and excretion. Therefore, it is important to study the pharmacokinetic changes in drugs under radiation. METHODS: To update data on the effects of ionizing radiation and non-ionizing radiation caused by environmental pollution or clinical treatments on the protein and mRNA expression of drug-metabolizing enzymes and drug transporters. Data and information on pharmacokinetic changes in drugs under radiation were analyzed and summarized. RESULTS: The effect of radiation on cytochrome P450 is still a subject of debate. The widespread belief is that higherdose radiation increased the expression of CYP1A1 and CYP1B1 of rat, zebrafish or human, CYP1A2, CYP2B1, and CYP3A1 of rat, and CYP2E1 of mouse or rat, and decreased that of rat's CYP2C11 and CYP2D1. Radiation increased the expression of multidrug resistance protein, multidrug resistance-associated protein, and breast cancer resistance protein. The metabolism of some drugs, as well as the clearance, increased during concurrent chemoradiation therapy, whereas the half-life, mean residence time, and area under the curve decreased. Changes in the expression of cytochrome P450 and drug transporters were consistent with the changes in the pharmacokinetics of some drugs under radiation. CONCLUSION: The findings of this review indicated that radiation caused by environmental pollution or clinical treatments can alter the pharmacokinetic characteristics of drugs. Thus, the pharmacokinetics of drugs should be rechecked and the optimal dose should be re-evaluated after radiation.

Magnetic resonance imaging evaluation of characteristics of vascular invasion in intermediate and advanced hepatic alveolar echinococcosis.

The objective of the present study was to provide a basis for the personalized treatment of intermediate and advanced hepatic alveolar echinococcosis (HAE) by elucidating the characteristics of vascular invasion and lesion growth. A total of 160 patients with intermediate and advanced HAE who were subjected to plain as well as contrast-enhanced 3.0-T magnetic resonance imaging prior to surgery were analyzed. Pathological and intra-operative observations of the subjects were also considered. The size and location of HAE lesions, vascular invasion characteristics and growth patterns were assessed. A total of 78 patients (48.75%) had lesions involving the S5-8 segment/partial right liver lobe, 21 (13.13%) had involvement in the S2-4 segment/partial left liver lobe and 61 (38.13%) had lesions that transcended the left and right liver lobes. Pathological examination revealed that the vascular invasion rates of the hepatic portal veins, intrahepatic veins (left, central and right vein, and inferior vena cava) and hepatic arteries were 51.88, 43.28 and 26.87%, respectively. Liver hilum invasion was observed in 128 patients (80.00%), 71 of which (44.38%) presented with invasion of the primary porta hepatis, 11 (6.88%) with invasion of the secondary porta hepatis and 46 (28.75%) with invasion of the primary as well as the secondary porta hepatis. In conclusion, the growth pattern of intermediate and advanced HAE is determined by the site, blood supply and activity of the lesion. The current study demonstrated that lesions tend to invade the intrahepatic venous system and porta hepatis, and to target veins rather than arteries.

Hypoxia Plays a Key Role in the Pharmacokinetic Changes of Drugs at High Altitude.

BACKGROUND: Hypoxia can alter the Pharmacokinetic (PK) characteristics of drugs, thereby affecting drug absorption, distribution, metabolism, and excretion. Environmental characteristics at high altitude include but are not limited to hypobaric hypoxia, low temperature, high solar radiation, and arid climate, all of which can adversely affect normal bodily functions. Therefore, it is important to study the pharmacokinetic changes of drugs at high altitude. METHOD: A systematic review of published studies was carried out to investigate the effects of hypoxia on the metabolic characteristics of some drugs and the activity and expression of drug-metabolizing enzymes in high-altitude hypoxic environments, and discussed the relevant mechanisms. RESULTS: The metabolism of most drugs decreases in high-altitude hypoxia, whereas Mean Residence Time (MRT), Half Time (T1/2), and Area Under the Curve (AUC) increase and Clearance (CL) decrease in this environment. The effect of hypoxia on CYP450 enzymes in animals is still a subject of debate. With the exception of CYP2C11 and CYP2C22, the widespread belief is that high-altitude hypoxia decreased the activity and expression of CYP1A1, CYP1A2, CYP2E1, and CYP3A1, and increased those of CYP3A6 and CYP2D1 in rats. The changes in the activity and expression of drug metabolizing enzymes are consistent with the changes in pharmacokinetics of some enzyme substrates in the high-altitude hypoxia environment. CONCLUSION: The findings of this review have indicated that hypoxia may play a key role in the PK changes of drugs at high altitude. It is suggested that patient living at or traveling to high altitude should be closely monitored, and the dosages of some drugs metabolized should be reduced.

Effects of yak-activated protein on hematopoiesis and related cytokines in radiation-induced injury in mice.

The aim of the present study was to investigate the protective effects of yak-activated protein on hematopoiesis and cytokine function in radiation-induced injury in mice. A total of 180 Kunming mice were randomly divided into three groups (A, B and C). Of these, 60 were randomly divided into a normal control group, a radiation model group, a positive control group and 3 yak-activated protein groups (high, medium and low dose groups; 10, 5 and 2.5 mg/kg, respectively). The other 120 mice were used for the subsequent experiments on days 7 and 14 following radiation. Yak-activated protein was administered orally to mice in the treatment groups and an equal volume of saline was administered orally to mice in the normal control and radiation model groups for 14 days. The positive control group received amifostine (150 mg/kg) via intraperitoneal injection. With the exception of the control group, the groups of mice received a 5 Gy quantity of X-radiation evenly over their whole body once. Changes in the peripheral hemogram, thymus and spleen indices, DNA content in the bone marrow, interleukin (IL)-2 and IL-6 levels, and the expression levels of B cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) following irradiation were assessed. The low dose of yak-activated protein significantly increased Spleen indices in mice 14 days after irradiation and the high and middle dose of yak-activated protein significantly increased Thymus indices in mice 14 days after irradiation (P<0.05) compared with the control group. In addition, hemogram results increased gradually in the low-yak-activated protein dose group and were significantly higher 7 days after irradiation compared with the radiation model group (P<0.05). The DNA content in the bone marrow was markedly increased in the yak-activated protein groups, and increased significantly in the low dose group at 7 days post-irradiation compared with the radiation model group (P<0.05). The IL-2 content was significantly increased in the yak-activated protein groups (P<0.05). Furthermore, Bcl-2 expression was increased and Bax expression was decreased (P<0.05). These results suggest that yak-activated protein exerts protective effects against radiation-induced injury in mice. The optimal effects of yak-activated protein were observed in the medium dose group 14 days after irradiation.