Photoactivatable nanogenerators of reactive species for cancer therapy.

In recent years, reactive species-based cancer therapies have attracted tremendous attention due to their simplicity, controllability, and effectiveness. Herein, we overviewed the state-of-art advance for photo-controlled generation of highly reactive radical species with nanomaterials for cancer therapy. First, we summarized the most widely explored reactive species, such as singlet oxygen, superoxide radical anion (O2 ●-), nitric oxide (●NO), carbon monoxide, alkyl radicals, and their corresponding secondary reactive species generated by interaction with other biological molecules. Then, we discussed the generating mechanisms of these highly reactive species stimulated by light irradiation, followed by their anticancer effect, and the synergetic principles with other therapeutic modalities. This review might unveil the advantages of reactive species-based therapeutic methodology and encourage the pre-clinical exploration of reactive species-mediated cancer treatments.

Merocyanine-paclitaxel conjugates for photothermal induced chemotherapy.

Small molecular nanomedicines that integrate the flexibility of self-assembly strategies and the advantages of a precise molecular structure, a high drug content and controlled drug release are effective diagnostic and therapeutic modalities. Herein, merocyanine-paclitaxel conjugates (MC-PTX) were developed and fabricated by using the degradable ester bonds as the linker. The as-prepared MC-PTX could self-assemble into nanoparticles (MC-PTX NPs) using the non-covalent molecular interaction via the nanoprecipitation method. MC-PTX NPs possess a favorable biological stability and can efficiently release the paclitaxel (PTX) activated by the heat of the photoactive material merocyanine under light illumination, as monitored using dynamic light scattering. The obtained MC-PTX NPs could be endocytosed into cancer cells and release PTX under laser irradiation in the cytoplasm, thus eliciting a satisfactory anticancer effect. Photothermal triggered degradation upon light illumination could enhance the chemotherapeutic efficacy of paclitaxel. The fluorescent nature of the NPs could visualize the internalization process. We believe that this robust nanomedicine offers a novel strategy to facilitate clinical translation for use as a small molecular chemotherapy nanomedicine.

Highly efficient near-infrared BODIPY phototherapeutic nanoparticles for cancer treatment.

BODIPYs are highly potential photoactive agents for cancer theragnostics. The rational design of BODIPY-based photoactive nanodrugs with high efficiency and near-infrared (NIR) absorption is imperative. Herein, we developed a donor-acceptor-donor (D-A-D) organic photosensitizer (PS) (BODIPY, named NBB), which possessed strong absorption in the NIR region due to the multi-intersection of intramolecular charge transfer (ICT), photoinduced electron transfer (PET), and heavy atom effects. Through a nanoprecipitation method, NBB nanoparticles (NPs) were facilely prepared. The as-prepared NBB NPs exhibited favorable water-stability and photostability. In particular, the outstanding photon absorption capacity endows the NPs with high photothermal conversion efficiency (η = 53.8%) and active singlet oxygen (1O2) generation ability upon 808 nm laser irradiation, and promotes their tumour inhibition efficiency via the combination of photothermal/photodynamic therapy (half-maximal inhibitory concentration IC50 = 8.11 and 7.77 µM for HeLa and HepG2 cells, respectively). Together with the favorable synthetic yield and excellent antitumour effect, we envision that this exploration can provide beneficial guidance for the clinical translation of BODIPY-based PSs for phototherapy.

Integration of metal-organic framework with a photoactive porous-organic polymer for interface enhanced phototherapy.

Porphyrin-based porous organic polymers are highly potential candidates for cancer theranostics. However, un-controllable particle size and unclear photoactive mechanisms have been deemed to be "Achilles' heels" for their biomedical application. Herein, a facile self-template strategy has been applied to integrate two types of porous materials to build the MOF@POP-PEG nanocomposite (named HUC-PEG). As-synthesized HUC-PEG exhibited controllable particle shape and size, good biocompatibility, and better colloidal stability. Importantly, synergy "0 + 1 > 1" interface effects have been demonstrated to simultaneously enhance both the generation of more singlet oxygen (1O2) for photodynamic therapy (PDT) and local hyperthermia for photothermal therapy (PTT), thus to achieve favorable proliferation inhibition of tumor cell both in vitro and in vivo. Moreover, the strong X-ray attenuating ability of Hf element and excellent photothermal conversion efficacy endow this nanocomposite with computed tomography (CT)/photothermal imaging functions. We believe that our ingenious design may open a new horizon for the preparation of nanoscale POP-based therapeutic agents and also realize a paradigm shift in the understanding of photoactive mechanism in porous materials.

Cynanchum bungei Decne and its two related species for "Baishouwu": A review on traditional uses, phytochemistry, and pharmacological activities.

ETHNOPHARMACOLOGICAL RELEVANCE: Cynanchum bungei Decne. (CB) (Asclepiadaceae) and its two related species Cynanchum auriculatum Royle ex Wight. (CA) and Cynanchum wilfordii (Maxim.) Hemsl. (CW) are well known Chinese herbal medicines known by the name Baishouwu. Among them, CB has long been used for nourishing the kidney and liver, strengthening the bones and muscles, and regulating stomachache. However, to date, no comprehensive review on Baishouwu has been published. AIM OF THE REVIEW: This review aims to provide a comprehensive summary on traditional uses, phytochemistry, pharmacology, and toxicology of the three herbal components of Baishouwu with the ultimate objective of providing a guide for future scientific and therapeutic potential use of Baishouwu. MATERIAL AND METHODS: A literature search was undertaken on CB, CA and CW by analyzing the information from scientific databases (SciFinder, Pubmed, Elsevier, Google Scholar, Web of Science, and Baidu Scholar). Information was also gathered from local classic herbal literatures and conference papers on ethnopharmacology and the information provided in this review has been obtained from peer-reviewed papers. RESULTS: Comparative analysis of literature search indicate that ethnopharmacological use of CB was recorded in China, however, CA and CW have been used in China, Korea and Japan. To date, 151 chemical compounds have been isolated from these species, and the major chemical constituents have been revealed to be acetophenones, C21-steroids, terpenoids, and alkaloids. These compounds and extracts have been proven to exhibit significant pharmacological activities, including anti-tumor, anti-inflammatory, immunomodulatory, hypolipidemic, anti-obesity, hepatoprotective, antifungal, antiviral, anti-depressant, vasodilating and estrogenic activities. CONCLUSIONS: CB, CA and CW collectively known as Baishouwu are valuable medicinal herbs with multiple pharmacological activities. The traditional use for nourishing liver is closely associated with the hepatoprotective activity. The available literature performs that various of the activity of Baishouwu can be attributed to acetophenones and C21-steroids. It is high time that more efforts should be focused on the underlying mechanisms of their beneficial bioactivities and the structure activity relationship of the constituents, as well as their potential synergistic and antagonistic effects. The proper toxicology evaluation is crucial to guarantee the safety, efficacy, and eligibility for medical use. Further research on the comprehensive evaluation of medicinal quality and the understanding of multi-target network pharmacology of Baishouwu is in great request.

A Review: The Bioactivities and Pharmacological Applications of Phellinus linteus.

Phellinus linteus is a popular medicinal mushroom that is widely used in China, Korea, Japan, and other Asian countries. P. linteus comprises various bioactive components, such as polysaccharides, triterpenoids, phenylpropanoids, and furans, and has proven to be an effective therapeutic agent in traditional Chinese medicine for the treatment and the prevention of various diseases. A number of studies have reported that P. linteus possesses many biological activities useful for pharmacological applications, including anticancer, anti-inflammatory, immunomodulatory, antioxidative, and antifungal activities, as well as antidiabetic, hepatoprotective, and neuroprotective effects. This review article briefly presents the recent progress made in understanding the bioactive components, biological activities, pharmacological applications, safety, and prospects of P. linteus, and provides helpful references and promising directions for further studies of P. linteus.

Photothermal-Controlled Generation of Alkyl Radical from Organic Nanoparticles for Tumor Treatment.

The therapeutic properties of light are well known for photodynamic or photothermal therapy, which could cause irreversible photodamage to tumor tissues. Although photodynamic therapy (PDT) has been proved in the clinic, the efficacy is not satisfactory because of complicated tumor microenvironments. For example, the hypoxia in solid tumor has a negative effect on the generation of singlet oxygen. To address the hypoxia issues in PDT, leveraging alkyl radical is an available option due to the oxygen-independent feature. In this work, a new kind of organic nanoparticles (tripolyphosphate (TPP)-NN NPs) from porphyrin and radical initiator is developed. Under near-infrared light irradiation, TPP-NN NPs will split and release alkyl radical, which could induce obvious cytotoxicity both in normal and hypoxia environment. The photothermal-controlled generation of alkyl radical could significantly inhibit the growth of cervical cancer and show ignorable systemic toxicity. This activatable radical therapy opens up new possibilities for the application of PDT in hypoxia condition.

Ultrafast synthesis of ultrasmall polyethylenimine-protected AgBiS2 nanodots by "rookie method" for in vivo dual-modal CT/PA imaging and simultaneous photothermal therapy.

Developing a biocompatible nanotheranostic platform integrating diagnostic and therapeutic functions is a great prospect for cancer treatment. However, it is still a great challenge to synthesize nanotheranostic agents using an ultra-facile method. In the research reported here, ultrasmall polyethylenimine-protected silver bismuth sulfide (PEI-AgBiS2) nanodots were successfully synthesized using an ultra-facile and environmentally friendly strategy (1 min only at room temperature), which could be described as a "rookie method". PEI-AgBiS2 nanodots show good monodispersity and biocompatibility. For the first time, PEI-AgBiS2 nanodots were reported as a powerful and safe nanotheranostic agent for cancer treatment. PEI-AgBiS2 nanodots exhibit excellent computed tomography (CT) and photoacoustic (PA) dual-modal imaging ability, which could effectively guide photothermal cancer therapy. Furthermore, PEI-AgBiS2 nanodots exhibit a high photothermal conversion efficiency (η = 35.2%). The photothermal therapy (PTT) results demonstrated a highly efficient tumor ablation ability. More importantly, the blood biochemistry and histology analyses verify that the PEI-AgBiS2 nanodots have negligible long-term toxicity. This work highlights that PEI-AgBiS2 nanodots produced using this extremely effective method are a high-performance and safe PTT agent. These findings open a new gateway for synthesizing nanotheranostic agents by using this ultra-facile method in the future.

Second Near-Infrared Conjugated Polymer Nanoparticles for Photoacoustic Imaging and Photothermal Therapy.

Photothermal conversion in the second near-infrared (NIR-II) window allows deeper penetration and higher exposure to lasers, but examples of NIR-II photothermal agents are mainly formulated by inorganic compounds. In view of the underlying influence of inorganic materials, a novel NIR-II photothermal nanoagent based on a narrow band gap D-A conjugated polymer (TBDOPV-DT) with 2,2-bithiophene as the donor and thiophene-fused benzodifurandione-based oligo( p-phenylenevinylene) as the acceptor has been developed. More importantly, TBDOPV-DT nanoparticles (TBDOPV-DT NPs) are demonstrated to combine excellent photoacoustic imaging (PAI) and photothermal therapy (PTT) ability. TBDOPV-DT NPs exhibit dramatic photostability and heating reproducibility with a photothermal conversion efficiency of 50%. Especially, the NPs possess a remarkable PTT effect toward cancer cells in vitro and can eliminate tumor cells completely in vivo under 1064 nm laser irradiation, while no appreciable side effects have been observed. This study achieves PAI-guided cancer therapy and sheds light on the future of using organic polymer NPs for the NIR-II PTT of cancer.

Nanoparticles based on glycyrrhetinic acid modified porphyrin for photodynamic therapy of cancer.

Self-assembled small molecules, as a novel form of drug presentation, have splendid capabilities for water stability and cell endocytosis. Photodynamic therapy (PDT) is regarded as a promising cancer treatment because it is less invasive and has fewer side effects. In this work, an amphiphilic glycyrrhetinic acid-porphyrin conjugate (TPP-GA) was designed and synthesized, and this could self-assemble into nanoparticles (TPP-GA NPs) in water. The morphology of the TPP-GA NPs was observed using transmission electron microscopy (TEM) and their stability in water was revealed by dynamic light scattering (DLS). The PDT effect of the TPP-GA NPs was confirmed by means of in vitro experiment, after photostability verification. It could be conceived that the application of TPP-GA NPs for PDT is a feasible choice and this work shows progress in the self-assembly of amphiphilic small organic molecules.

PEG-Induced Synthesis of Coordination-Polymer Isomers with Tunable Architectures and Iodine Capture.

Controllable synthesis of coordination polymer (CP) isomers and revealing their structure-property relationships remain enormous challenges. Three new supramolecular isomers have been synthesized by tuning the poly(ethylene glycol) (PEG) content in the feed. These supramolecular isomers have the same framework formula of [Cu2 I2 (tppe)] and different architectures from the classical 2D stacking framework to a 3D entangled system with the coexistence of interpenetration and polycatenation, and a 3D topological framework. Interestingly, these CPs could be utilized for capturing iodine molecules. According to multiple complementary experiments and crystallographic analyses, iodine capture is mainly based on halogen-bond interactions in the inorganic {Cu2 I2 } building blocks of the framework. The present study describes a structure-property relationship in supramolecular isomerism with distinct topological structures.

Olive oil exhibits osteoprotection in ovariectomized rats without estrogenic effects.

The present study was designed to evaluate the effect of olive oil on bone and uterus in ovariectomized rats. A total of 34 surgically ovariectomized or sham-operated virgin Sprague-Dawley rats were divided into four groups: i) Sham-operated control rats (sham group); ii) Ovariectomized rats (OVX group); iii) Olive oil-supplemented ovariectomized rats (olive group); and iv) Diethylstilbestrol-supplemented ovariectomized rats (E2 group). At 12 weeks following left ventricular blood sacrificed to detect plasma estradiol (E2), interleukin-1ß (IL-1ß) and IL-6 levels. Bone mineral density (BMD) of the lumbar spine was evaluated using dual-energy X-ray absorptiometry, and the left femur proximal 1/3 slices were observed using transmission electron microscopy. Uterine wet weight and the uterus index (ratio of uterine wet weight and body weight) were compared, and the uterine endometrium was observed using a light microscope. In the OVX group, serum E2 was significantly lower and IL-1ß and IL-6 levels were significantly higher compared with the sham group. By contrast, serum E2 levels increased and IL-1ß levels decreased in the olive group, but showed no significant difference compared with the sham group. The lumbar spine BMD in the olive group was increased compared with OVX group. Electron microscopy revealed sparse collagen fibers in the OVX group, with decreased density and multi-cavity, showing pathological features of osteoporosis. By contrast, the situation was improved in the E2 and olive groups, in which organelles such as the rough endoplasmic reticulum, mitochondria and Golgi apparatus were visible and active. Compared with the sham group rats, the uterine wet weight and uterine index decreased in the OVX and olive groups; however, no statistically significant difference was observed in the E2 group. Furthermore, endometrial hyperplasia was not observed in the olive group, which were apparently different from E2 group. The present results suggest that olive oil can effectively reduce bone loss in ovariectomized rats, and with no or only mild effects on the uterine endothelium.

Detection of hypervascular hepatocellular carcinoma: Comparison of multi-detector CT with digital subtraction angiography and Lipiodol CT.

AIM: The purpose of this study was to compare the diagnostic accuracy of biphasic multi-detector row helical computed tomography (MDCT), digital subtraction angiography (DSA) and Lipiodol computed tomography (CT) in detection of hypervascular hepatocellular carcinoma (HCC). METHODS: Twenty-eight patients with nodular HCC underwent biphasic MDCT examination: hepatic arterial phase (HAP) 25 s and portal venous phase (PVP) 70 s after injection of the contrast medium (1.5 mL/kg). They also underwent hepatic angiography and intra-arterial infusion of iodized oil. Lipiodol CT was performed 3-4 wk after infusion. MDCT images were compared with DSA and Lipiodol CT images for detection of hepatic nodules. RESULTS: The three imaging techniques had the same sensitivity in detecting nodules >20 mm in diameter. There was no significant difference in the sensitivity among HAP-MDCT, Lipiodol CT and DSA for nodules of 10-20 mm in diameter. For the nodules <10 mm in diameter, HAP-MDCT identified 47, Lipiodol CT detected 27 (chi2 = 11.3, P = 0.005<0.01, HAP-MDCT vs Lipiodol CT) and DSA detected 16 (chi2 = 9.09, P = 0.005<0.01 vs Lipiodol CT and chi2 = 29.03, P = 0.005<0.01vs HAP-MDCT). However, six nodules <10 mm in diameter were detected only by Lipiodol CT. CONCLUSION: MDCT and Lipiodol CT are two complementary modalities. At present, MDCT does not obviate the need for DSA and subsequent Lipiodol CT as a preoperative examination for HCC.

Successful management of a benign anastomotic colonic stricture with self-expanding metallic stents: a case report.

AIM: To assess the effectiveness of and complications associated with metallic stent placement for treatment of anastomotic colonic strictures. METHODS: A 46-year-old man undergoing two procedures of surgery for perforation of descending colon due to a traffic accident presented with pain, abdominal distention, and inability to defecate. Single-contrast barium enema radiograph showed a severe stenosis in the region of surgical anastomosis and the patient was too weak to accept another laparotomy. Under fluoroscopic and endoscopic guidance, we placed two metallic stents in the stenosis site of the anastomosis of the patient with anastomotic colonic strictures. RESULTS: In this case of postsurgical stenosis, the first stent relieved the symptoms of obstruction, but stent migration happened on the next day so an additional stent was required to deal with the stricture and relieve the symptoms. CONCLUSION: This case confirms that metallic stenting may represent an effective treatment for anastomotic colonic strictures in the absence of other therapeutic alternatives.

Hepatocellular carcinoma treated with interventional procedures: CT and MRI follow-up.

In the past decade, a variety of interventional procedures have been employed for local control of hepatocellular carcinoma (HCC). These include transcather arterial chemoembolization (TACE) and several tumour ablation techniques, such as percutaneous ethanol injection (PEI), radio-frequency ablation (RFA), or percutaneous microwave coagulation therapy (PMC), laser-induced interstitial thermotherapy (LITT), etc. For a definite assessment of the therapeutic efficacy of interventional procedures, histological examination using percutaneous needle biopsy may be the most definite assessment of the therapeutic efficacy of interventional therapy, however, it is invasive and the specimen retrieved does not always represent the entire lesion owing to sampling errors. Therefore, computed tomography (CT) and magnetic resonance imaging (MRI) play a crucial role in follow-up of HCC treated by interventional procedures, by which the local treatment efficacy, recurrent disease and some of therapy-induced complications are evaluated. Contrast enhanced axial imaging (CT or MR imaging) may be the most sensitive test for assessing the therapeutic efficacy. The goal of the review was to describe the value of CT and MRI in the evaluation of interventional treatments.