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Recently, nanoformulations have been widely applied in the delivery of organic photothermal agents (OPTAs) for cancer therapy to prolong blood circulation or improve tumor-targeting capacity. However, the systematic evaluations of their effects on the photothermal behavior of OPTAs are limited, especially for different types of nanoparticle systems. Herein, we prepared two kinds of nanoparticles (BSA and PEG nanoparticles (NPs)) to load an OPTA, a cyanine photosensitizer (IR780-O-TPE), and investigated their photothermal response, organelle targeting, and in vivo therapeutic efficacy. Due to different assembly forms, the two NPs showed distinct morphological changes after exposure to laser or hyperthermia. Under laser irradiation at 808 nm, BSA NPs could release IR780-O-TPE more efficiently than PEG NPs. We speculate that this phenomenon is probably caused by dual-responsive release of IR780-O-TPE from BSA NPs against light and hyperthermia. Moreover, IR780-O-TPE/BSA NPs were highly mitochondria-targeting and therefore displayed significant inhibition of cell viability. In contrast, IR780-O-TPE/PEG NPs were "shell-core" nanostructures and more stable under laser stimulation. As a consequence, the mitochondria-targeting and anticancer photothermal therapy by IR780-O-TPE/PEG NPs was less obvious. This study revealed the significance of nanocarrier design for OPTA delivery and demonstrated that BSA NPs could release IR780-O-TPE more effectively for efficient photothermal therapy. We also believe that the dual-responsive release of OPTAs from NPs can provide an effective strategy to promote anticancer photothermal treatment.

With the rapid development of nanotechnology, researchers have designed a variety of intelligent nanodelivery systems to enhance tumor targeting of anticancer drugs. However, increased tumor accumulation does not indicate deeper penetration in the tumor tissue, without which the tumor cells in the core area cannot be sufficiently killed. Herein, we develop a size-controllable nanoparticle system for deep-penetrating cancer therapy, which will be programmably disassembled with the decrease of the pH from the normal tissue to the tumor microenvironment and to the intracellular area. The integrated nanoparticle is composed of a gold nanoparticle (GNP, ∼30 nm) and a tetrahedral DNA nanostructure (TDN, ∼25 nm) loaded with doxorubicin (DOX). Initially, the nanoparticles maintain a larger size (∼100 nm) to accumulate in the tumor through the enhanced permeability and retention effect. At a pH of about 6.5 at the tumor microenvironment, with the linkage of DNA sequences converting into a triplex structure, the TDNs detach from the GNP and penetrate deeply into the tumor interstitium and then are internalized into the cells. Finally, in acidic lysosomes with pH 5.0, the TDNs release DOX by forming an i-motif structure. This nanosmart delivery system thus shows effective deep penetration into the tumor core with good antitumor efficacy and satisfactory biocompatibility and provides new insights into the development of intelligent nanosystems for anti-cancer treatment.

Haoran Gao,1,&ast; Chao Chen,2,&ast; Xiujie Zhao,1 Lei Zhao,1 Xiaoming Zheng,1 Haibin Sun,1 Hua Bao,1 Baojun Wang2 1Department of Neurology, Hulunbuir People’s Hospital, Hulunbuir, 021000, People’s Republic of China; 2Department of Neurology, Center Hospital of Baotou, Baotou, 014040, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hua Bao, Department of Neurology, Hulunbuir People’s Hospital, No. 20 Shengli Street, Hailar District, Hulunbuir, 021000, People’s Republic of China, Tel +86-0470-3997068, Email baohuabh81@126.com Baojun Wang, Department of Neurology, Center Hospital of Baotou, No. 61 of Huancheng Road, Donghe District, Baotou, 014040, People’s Republic of China, Tel/Fax +86-0472-6955346, Email wangbaojunwbj96@126.comObjective: To study the correlation between the adenosine triphosphate (ATP) content in the hippocampus of rats and delayed encephalopathy after acute carbon monoxide (CO) poisoning.Methods: A total of 40 male Wistar rats weighing 180– 230g, in accordance with the random number table, were selected and divided into the delayed encephalopathy after acute carbon monoxide poisoning (DEACMP: Rats with cognitive impairment after carbon monoxide poisoning) group (n = 32) and the control group (n = 8). A DEACMP rat model was generated by inhalation of CO. The Morris water maze evaluated the ability to learn and memorize in rats. The changes in neurons in the hippocampus of the rats were observed by hematoxylin-eosin (HE) staining. Lastly, the ATP content in the hippocampus of the rats was measured by high-performance liquid chromatography (HPLC).Results: The ATP content of the experimental group was significantly higher than that of the control group in the hippocampus of the rat model, so the difference was statistically significant (P < 0.05); the intra-group comparison was made for the ATP content in the experimental group, and the difference was statistically significant as group 21d > group 14d > group 7d (P < 0.05); and no significant difference was found between group 21d and group 28d (P > 0.05).Conclusion: The changes in the ATP content in the hippocampus of the rats are correlated with the occurrence of delayed encephalopathy after acute carbon monoxide poisoning; it may take part in the pathogenesis of DEACMP. This offers some elicitation to the prevention and treatment of the disease.Keywords: carbon monoxide poisoning, delayed encephalopathy, ATP, HPLC

In recent years, cancer phototherapy has been extensively studied as noninvasive cancer treatment. To present efficient recognition toward cancer cells, most photosensitizers (PSs) are required to couple with tumor-targeted ligands. Interestingly, the heptamethine cyanine IR780 displays an intrinsic tumor-targeted feature even without modification. However, the photothermal efficacy and photostability of IR780 are not sufficient enough for clinical use. Herein, we involve a twisted structure of tetraphenylethene (TPE) between two molecules of IR780 to improve the photothermal conversion efficiency (PCE). The obtained molecule T780T shows strong near-infrared (NIR) fluorescence and improved PCE (38.5%) in the dispersed state. Also, the photothermal stability and ROS generation capability of T780T at the NIR range (808 nm) are both promoted. In the aqueous phase, the T780T was formulated into uniform nanoaggregates (∼200 nm) with extremely low fluorescence and PTT response, which would reduce in vivo imaging background and side effect of PTT response in normal tissues. After intravenous injection into tumor-bearing mice, the T780T nanoaggregates display high tumor accumulation and thus remarkably inhibit the tumor growth. Moreover, the enhanced photostability of the T780T allows for twice irradiation after one injection and leads to more significant tumor inhibition. In summary, our study presents a tumor-targeted small-molecule PS for efficient cancer therapy and brings a new design of heptamethine cyanine PS for potential clinical applications.

This paper analyzes a condition-based maintenance (CBM) model for a system with two heterogeneous components in which degradation follows a bivariate gamma process. Unlike the traditional CBM formulation that assumes an infinite planning horizon, this paper evaluates the maintenance cost in a finite planning horizon, which is the practical case for most systems. In the proposed CBM policy, both components are periodically inspected and a preventive or corrective replacement might be carried out based on the state of degradation at inspection. The CBM model is formulated as a Markov decision process (MDP) and dynamic programming is used to compute the expected maintenance cost over a finite planning horizon. The expected maintenance cost is minimized with respect to the preventive replacement thresholds for the two components. Unlike an infinite-horizon CBM problem, which leads to a stationary maintenance policy, the optimal policy in the finite-horizon case turns out to be non-stationary in the sense that the optimal actions vary at each inspection epoch. A numerical example is presented to illustrate the proposed model and investigate the influence of economic dependency and correlation between the degradation processes on the optimal maintenance policy. Numerical results show that a higher dependence between the degradation processes actually reduces the maintenance cost, while a higher economic dependence leads to higher preventive replacement thresholds.

The Markov decision process (MDP) model has been widely studied and used in sequential decision making problems. In particular, it has been proved to be effective in maintenance policy optimization problems where the system state is supposed to continuously evolve under sequential maintenance policies. In traditional MDP models for maintenance, the long-run expected total discounted cost is concerned as the objective function. The maintenance manager’s target is to evaluate an optimal policy that incurs the minimum expected total discounted cost through the corresponding MDP model. However, a significant drawback of these existing MDP-based maintenance strategies is that they fail to incorporate and characterize the safety issues of the system during the maintenance process. Therefore, in some applications that are sensitive to functional risks, such strategies fail to accommodate the requirement of risk awareness. In this study, we apply the concept of risk-aversion in the MDP maintenance model to develop risk-aware maintenance policies. Specifically, we use risk functions to measure some indexes of the system that reflect the safety level and formulate a safety constraint. Then, we summarize the problem as a constrained MDP model and use the linear programming approach to evaluate the proposed risk-aware optimal maintenance policy under concern.

Helicobacter pylori (H. pylori) infection has been the leading cause of gastric cancer development. In recent years, the resistance of H. pylori against antibiotic treatment has been a great challenge for most countries worldwide. Since biofilm formation is one of the reasons for the antibiotic resistance of H. pylori, and phototherapy has emerged as a promisingly alternative antibacterial treatment, herein the bacteria-targeted near-infrared (NIR) photosensitizer (T780T-Gu) by combining positively-charged guanidinium (Gu) with an efficient phototherapeutic agent T780T is developed. The proposed molecule T780T-Gu exhibits synergistic photothermal therapy/photodynamic therapy effect against both H. pylori biofilms and multidrug-resistant (MDR) clinical strains. More importantly, the phototherapy mechanism of T780T-Gu acquired by the RNA-seq analysis indicates that structural deficiency as well as a decrease in metabolism and defense activity are the possible reasons for the efficient H. pylori phototherapy.