Inorganic nanomaterials are widely applied in the diagnosis and comprehensive therapy of multiple diseases, in particular tumors, because of their unique nano-characters. Superparamagnetic iron oxide nanoparticles, upconversion nanoparticles and noble metal nanoparticles are the representative ones, possessing excellent magnetic, optical and thermal properties respectively. In this review, we focus on the applications of the three kinds of inorganic nanomaterials in bio-detection in vitro, molecular imaging in vivo, targeting anti-tumor drug delivery and tumor therapy. The advantages as well as the limitations of them in tumor theranostics are discussed. By this way, some references and suggestions are provided to develop more biocompatible inorganic nanomaterials with better theranostic effects, which will promote their clinical transformation.

Folic acid (FA) has long been used as a specific targeting agent since many cancer cells overexpress folate receptors (FRs). Herein, novel functionalities of FA will be explored: directed self-assembly of nanoparticles for drug delivery together with pH responsive release. By conjugating with dextran (DEX), DEX-FA exerts a pH dependent self-assembly behavior: it self-associates into nanoparticles (NPs) around physiological pH (pH 7) and disassembles at higher pH (pH > 9). Doxorubicin (DOX), a model antitumor drug, has been successfully encapsulated via electrostatic interactions between DOX and FA. Moreover, the pH responsive release behaviors of DOX are controlled by FA. The DOX@DEX-FA NPs exhibit typical FA-FRs-mediated endocytosis in vitro and targeted delivery in vivo, altogether contributing to an enhanced antitumor efficacy, alleviated side effects, and elongated overall survival in a 4T1 subcutaneous tumor-bearing mouse model. The DOX@DEX-FA NPs have been demonstrated to be a simple, safe and efficient nanoplatform, holding significant translation potential for treating FR-overexpressing cancers. This study may present novel functionalities of FA in cancer-targeted nanotherapeutics.

Selenium is an essential trace element for human being and its biological functions are mainly carried out by selenoproteins. Selenoprotein S (SELENOS) mainly localizes to the endoplasmic reticulum (ER) membrane and is involved in the process of ER-associated degradation. The biological functions of SELENOS are mainly carried out through the coiled-coil domain and C-terminal disordered structure region containing selenocysteine residue in the cytosol. A large number of in vitro studies have shown that SELENOS participates in the regulation of oxidative stress, ER stress and inflammation, and thus is possibly involved in the development of cardiovascular disease, type 2 diabetes, and Alzheimer's disease. Furthermore, the observational epidemiological studies have found that many single nucleotide polymorphisms in the SELENOS gene are closely associated with cardiovascular disease and cancer. This paper reviews the structure and function of SELENOS and its relationship with diseases. The problems remaining to be solved are summarized and the future developments are prospected.

Herein, reduction-responsive disintegratable nanoclusters (NCs) were prepared as a novel nanovehicle for targeted drug delivery. The NCs, with a diameter of ∼170 nm, were self-assembled from hydrophobically modified and iRGD decorated hydroxyethyl starch (iRGD-HES-SS-C18). DOX was loaded into the NCs as a model drug. DOX@iRGD-HES-SS-C18 NCs can disintegrate into smaller ones and release DOX under reduction stimuli. Due to the ligand-receptor binding interactions between iRGD and integrin αV, DOX@iRGD-HES-SS-C18 NCs can specifically bind to the cell membranes of HepG-2 and 4T1 cells (integrin αV positive), resulting in enhanced cellular uptake as compared to DOX@HES-SS-C18 NCs. After cellular internalization, the NCs were transported to endosomes/lysosomes in which the reductive environment triggered the disintegration and DOX release. As a consequence, DOX@iRGD-HES-SS-C18 NCs exhibited an enhanced antitumor effect as compared to DOX@HES-SS-C18 NCs and free DOX, in an in vitro antitumor activity study. The reduction-responsive disintegratable NCs reported here were proved to be a safe and efficient nanoplatform, holding significant translation potential for tumor-targeted drug delivery.

Bio-inspired polydopamine (PDA) based nanomaterials, particularly nanoparticles (NPs), received tremendous attention and have been applied to various fields, including drug delivery. Nonetheless, bare PDA NPs will aggregate in physiological conditions and can be hardly applied for in vivo explorations. Herein, we present the preparation of novel hydroxyethyl starch coated PDA (HES-PDA) NPs for cancer chemotherapy. The frequently used PEG-modified PDA (PEG-PDA) NPs are also manufactured as a control and doxorubicin (DOX) is chosen as a model drug. The stability, drug loading capacity, lyophilization and rehydration property, biodistribution, in vitro and in vivo anti-tumor efficacy, and toxicity of DOX-loaded HES-PDA (DOX@HES-PDA NPs) are investigated. Collectively, DOX@HES-PDA NPs, similar to DOX@PEG-PDA NPs, show potent antitumor efficacy and dramatically mitigate toxicity associated with DOX. The HES-PDA NPs reported herein represent a novel biodegradable multifunctional nano-drug formulation, with significant translation potentials, for cancer chemotherapy against a wide spectrum of cancers.

Ultrasound was used to synthesize nano-structures of [Ni(bpzB)2]2(1), a new two-nuclear discrete-coordination compound of divalent nickel with bis-pyrazolyl borate(bpzB). The nanostructure was characterized by scanning electron microscopy, X-ray powder diffraction, infrared, and elemental analysis. The single-crystal X-ray data show that the coordination number of Ni(II) ions is four (Ni1N4 and Ni2N4) with square planar geometry. The supramolecular features in these complexes are guided and controlled by weak directional intermolecular interactions. The discrete molecules interact with each other through labile interactions, creating a 3D supramolecular framework.

羟乙基淀粉(HES)是临床上常用的血浆扩容剂,具有优异的水溶性、生物相容性及安全性.因其独特的生物学特性,HES可用于肿瘤诊疗药物的体内靶向输送.通过耦联或包埋等方式,HES可以增加药物水溶性及稳定性,延长半衰期,提高肿瘤靶向性,减少正常组织药物摄取并降低毒副作用.HES丰富的羟基官能团还可用于纳米药物表面修饰,实现多功能联合给药.HES在抗肿瘤纳米药物基础研究与临床转化具有巨大潜力.

Heterogeneous distribution of drug inside tumor is ubiquitous, causing regional insufficient chemotherapy, which might be the hotbed for drug resistance, tumor cell repopulation and metastasis. Herein, we verify, for the first time, that heterogeneous drug distribution induced insufficient chemotherapy would accelerate the process of epithelial mesenchymal transition (EMT), consequently resulting in the promotion of tumor metastasis. To eliminate the insufficient chemotherapy promoted metastasis, we conceived a co-delivery strategy by hydroxyethyl starch-polylactide (HES-PLA) nanoparticle, in which DOX and TGF-β receptor inhibitor, LY2157299 (LY), were administered together. In vitro and in vivo studies demonstrate that this co-delivery strategy can simultaneously suppress primary tumor and distant metastasis. Further study on immunofluorescence images of primary tumor verifies that low dose of DOX exasperates the EMT process, whereas the co-delivery nanoparticle can dramatically inhibit the progression of EMT. We reveal the impact of heterogeneous drug distribution on tumor metastasis and develop an effective co-delivery strategy to suppress the metastasis, providing guidance for clinical cancer therapy.

Paclitaxel (PTX) is an effective antineoplastic agent and shows potent antitumor activity against a wide spectrum of cancers. Yet, the wide clinical use of PTX is limited by its poor aqueous solubility and the side effects associated with its current therapeutic formulation. To tackle these obstacles, we report, for the first time, α-amylase- and redox-responsive nanoparticles based on hydroxyethyl starch (HES) for the tumor-targeted delivery of PTX. PTX is conjugated onto HES by a redox-sensitive disulfide bond to form HES-SS-PTX, which was confirmed by results from NMR, high-performance liquid chromatography-mass spectrometry, and Fourier transform infrared spectrometry. The HES-SS-PTX conjugates assemble into stable and monodispersed nanoparticles (NPs), as characterized with Dynamic light scattering, transmission electron microscopy, and atomic force microscopy. In blood, α-amylase will degrade the HES shell and thus decrease the size of the HES-SS-PTX NPs, facilitating NP extravasation and penetration into the tumor. A pharmacokinetic study demonstrated that the HES-SS-PTX NPs have a longer half-life than that of the commercial PTX formulation (Taxol). As a consequence, HES-SS-PTX NPs accumulate more in the tumor compared with the extent of Taxol, as shown in an in vivo imaging study. Under reductive conditions, the HES-SS-PTX NPs could disassemble quickly as evidenced by their triggered collapse, burst drug release, and enhanced cytotoxicity against 4T1 tumor cells in the presence of a reducing agent. Collectively, the HES-SS-PTX NPs show improved in vivo antitumor efficacy (63.6 vs 52.4%) and reduced toxicity in 4T1 tumor-bearing mice compared with those of Taxol. These results highlight the advantages of HES-based α-amylase- and redox-responsive NPs, showing their great clinical translation potential for cancer chemotherapy.

Atherosclerosis and related cardiovascular diseases (CVDs) represent the greatest threats to human health worldwide. Selenium, an essential trace element, is incorporated into selenoproteins that play a crucial role in human health and disease. Although findings from a limited number of randomized trials have been inconsistent and cannot support a protective role of Se supplementation in CVDs, prospective observational studies have generally shown a significant inverse association between selenium or selenoprotein status and CVD risk. Furthermore, a benefit of selenium supplementation in the prevention of CVDs has been seen in population with low baseline selenium status. Evidence from animal studies shows consistent results that selenium and selenoproteins might prevent experimental atherosclerosis, which can be explained by the molecular and cellular effects of selenium observed both in animal models and cell cultures. Selenoproteins of particular relevance to atherosclerosis are glutathione peroxidases, thioredoxin reductase 1, selenoprotein P, selenoprotein S. The present review is focusing on the existing evidence that supports the concept that optimal selenium intake can prevent atherosclerosis. Its underlying mechanisms include inhibiting oxidative stress, modulating inflammation, suppressing endothelial dysfunction, and protecting vascular cells against apoptosis and calcification. However, the benefit of selenium supplementation in the prevention of atherosclerosis remains insufficiently documented so far. Future studies with regard to the effects of selenium supplementation on atherosclerosis should consider many factors, especially the baseline selenium status, the dose and forms of selenium supplementation, and the selenoprotein genotype. Additionally, much more studies are needed to confirm the roles of selenoproteins in atherosclerosis prevention and clarify the underlying mechanisms.

Doxorubicin (DOX)-induced co-assembling nanomedicines (D-PNAx) with temperature-sensitive PNAx triblock polymers have been developed for regional chemotherapy against liver cancer via intratumoral administration in the present work. Owing to the formation of insoluble DOX carboxylate, D-PNAx nanomedicines showed high drug-loading and entrapment efficacy via a simple mixing of doxorubicin hydrochloride and PNAx polymers. The sustained releasing profile of D-PNA100 nanomedicines indicated that only 9.4% of DOX was released within 1day, and 60% was released during 10days. Based on DOX-induced co-assembling behavior and their temperature sensitive in-situ-forming hydrogels, D-PNA100 nanomedicines showed excellent antitumor activity against H22 tumor using intratumoral administration. In contrast to that by free DOX solution (1.13±0.04 times at 9days) and blank PNA100 (2.11±0.34 times), the tumor volume treated by D-PNA100 had been falling to only 0.77±0.13 times of original tumor volume throughout the experimental period. In vivo biodistribution of DOX indicated that D-PNA100 nanomedicines exhibited much stronger DOX retention in tumor tissues than free DOX solution via intratumoral injection. D-PNA100 nanomedicines were hopeful to be developed as new temperature sensitive in-situ-forming hydrogels via i.t. injection for regional chemotherapy.

An expanded triptycene (hexaphenylbenzene based triptycene) monomer was synthesized from triiodotriptycene. Using this monomer, two kinds of organic microporous polymers HTPs (HTP-A and HTP-B) were prepared by Friedel-Crafts and Scholl reactions. Their structure and properties were characterized by FT-IR, solid C-13 NMR, powder XRD, SEM, TEM and gas absorption. Nitrogen sorption analysis displayed that the BET surface areas are 569 and 914 m(2) g(-1) for HTP-A and HTP-B, respectively. For HTP-B, they can reversibly absorb 1.09 wt % H-2 (1.0 bar and 77 K) and 10.3 wt% CO2 (1.0 bar and 273 K), respectively. (C) 2015 Elsevier Ltd. All rights reserved.

Doxorubicin (DOX) is one of the most potent anticancer agents in cancer chemotherapy, but the clinical use of DOX is restricted by its severe side effects caused by nonspecific delivery. To alleviate the side effects and improve the antitumor efficacy of DOX, a novel redox-sensitive hydroxyethyl starch-doxorubicin conjugate, HES-SS-DOX, with diameter of 19.9 ± 0.4 nm was successfully prepared for tumor targeted drug delivery and GSH-mediated intracellular drug release. HES-SS-DOX was relatively stable under extracellular GSH level (∼2 μM) but released DOX quickly under intracellular GSH level (2-10 mM). In vitro cell study confirmed the GSH-mediated cytotoxicity of HES-SS-DOX. HES-SS-DOX exhibited prolonged plasma half-life time and enhanced tumor accumulation in comparison to free DOX. As a consequence, HES-SS-DOX exhibited better antitumor efficacy and reduced toxicity as compared to free DOX in the in vivo antitumor activity study. The redox-sensitive HES-SS-DOX was proved to be a promising prodrug of DOX, with clinical potentials, to achieve tumor targeted drug delivery and timely intracellular drug release for effective and safe cancer chemotherapy.

As an important hallmark in cancer progress, inflammation attracts more and more interests in recent years. Lots of evidences support the positive effect of n-3 PUFA in inflammation-associated diseases, the supplement of these fatty acids is thought to be promising in the prevention and treatment of cancers. In this review, we summarize some current knowledge of the mechanisms by which n-3 PUFA are thought to attenuate cancer associated inflammation, and we also introduce the current situation of n-3 PUFA in clinic.

Concentrated p(N-isopropylacrylamide) (PNIPAM) nanogel dispersions exhibited rich temperature-sensitive sol-gel phase transition behavior. In the present work, the influence of electrostatic forces between nanogel particles, including attraction and repulsion, on the sal-gel phase transition behavior of PNIPAM nanogel dispersions has been studied. Both oppositely charged nanogels with core-shell structures (NIA and PND nanogels) were synthesized, and their shell charges were calculated to -0.33 and 0.082 mmol/g by potentiometric titration method. When mixed with various ratio of negative and positive charge (NC value), the resultant mixture dispersions of NIA and PND nanogel (OCNs) exhibited different aggregating behavior from NIA and PND nanogels. OCN-e aggregates (NC value =1/4), which exhibited temperature-independence of electric neutrality, had the maximum size, about 1.9-2.2 times larger than NIA or PND nanogels. Concentrated OCN-e dispersions exhibited stronger ability to form shrunken gel. Its CGC was about 2.0 wt%, 4-times lower than that of NIA and PND nanogels (about 8.0 wt%). In vitro and in vivo gelling results indicated that OCN-e aggregates could form free-standing gel with good mechanical strength, and were promising to be developed as new in situ gelling system. (C) 2015 Elsevier B.V. All rights reserved.

Surgical resection is the primary mode for glioma treatment, while gross total resection is difficult to achieve, due to the invasiveness of the gliomas. Meanwhile, the tumor-resection region is closely related to survival rate and life quality. Therefore, we developed optical/magnetic resonance imaging (MRI) bifunctional targeted micelles for glioma so as to delineate the glioma location before and during operation. The micelles were constructed through encapsulation of hydrophobic superparamagnetic iron oxide nanoparticles (SPIONs) with polyethylene glycol-block-polycaprolactone (PEG-b-PCL) by using a solvent-evaporation method, and modified with a near-infrared fluorescent probe, Cy5.5, in addition to the gliomatargeting ligand lactoferrin (Lf). Being encapsulated by PEG-b-PCL, the hydrophobic SPIONs dispersed well in phosphate-buffered saline over 4 weeks, and the relaxivity (r(2)) of micelles was 215.4 mM(-1).s(-1), with sustained satisfactory fluorescent imaging ability, which might have been due to the interval formed by PEG-b-PCL for avoiding the fluorescence quenching caused by SPIONs. The in vivo results indicated that the nanoparticles with Lf accumulated efficiently in glioma cells and prolonged the duration of hypointensity at the tumor site over 48 hours in the MR image compared to the nontarget group. Corresponding with the MRI results, the margin of the glioma was clearly demarcated in the fluorescence image, wherein the average fluorescence intensity of the tumor was about fourfold higher than that of normal brain tissue. Furthermore, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay results showed that the micelles were biocompatible at Fe concentrations of 0-100 mu g/mL. In general, these optical/MRI bifunctional micelles can specifically target the glioma and provide guidance for surgical resection of the glioma before and during operation.

In recent years immunotherapy has been developed as a promising oncotherapy strategy after surgery, chemotherapy and radiotherapy. Immunotherapy has been widely used in the treatment of cancer including a variety of approaches. It is interesting that the overall efficiency of therapeutic cancer vaccines can be greatly improved when nanoparticle-based adjuvants are used. Significant efforts have been made to synthesize diverse nanoparticles which can fundamentally achieve surface modification and functionalization. In this review, we introduce the role of multifunctional nanoparticle-based adjuvants used in cancer vaccines, particularly focusing on synthesis methods of different types of nanoparticles and therapeutic effects of vaccines. In addition, some new ideas about nanotechnology used in cancer immunotherapy are summarized. Finally, the preliminary analysis and perspective on applying nanotechnology to overcoming the challenges of cancer vaccines are presented.

Catalpol, a bioactive component from the root of Rehmannia glutinosa, has been shown to possess hypoglycemic effects in type 2 diabetic animal models, however, the underlying mechanisms remain poorly understood. Here we investigated the effect of catalpol on high-fat diet (HFD)-induced insulin resistance and adipose tissue inflammation in mice. Oral administration of catalpol at 100 mg/kg for 4 weeks had no effect on body weight of HFD-induced obese mice, but it significantly improved fasting glucose and insulin levels, glucose tolerance and insulin tolerance. Moreover, macrophage infiltration into adipose tissue was markedly reduced by catalpol. Intriguingly, catalpol also significantly reduced mRNA expressions of M1 pro-inflammatory cytokines, but increased M2 anti-inflammatory gene expressions in adipose tissue. Concurrently, catalpol significantly suppressed the c-Jun NH2-terminal kinase (JNK) and nuclear factor-kappa B (NF-κB) signaling pathways in adipose tissue. Collectively, these results suggest that catalpol may ameliorate HFD-induced insulin resistance in mice by attenuating adipose tissue inflammation and suppressing the JNK and NF-κB pathways, and thus provide important new insights into the underlying mechanisms of the antidiabetic effect of catalpol.

Drug resistance is the major cause of failure of cancer chemotherapy in ovarian cancer. However, the molecular mechanisms on the regulation of drug resistance are not fully understood. Here we showed that Trx1 and FOXO1 were involved in paclitaxel (PTX)-induced drug resistance in ovarian cancer A2780 cells. PTX induced reactive oxygen species (ROS) and resulted in Trx1 and FOXO1 nuclear translocation. We further found that Trx1 bound to FOXO1 and enhanced FOXO1 transcriptional activity; however Trx1 C69S mutant which is barely detected in the nucleus downregulated Trx1–FOXO1 interaction and Trx1-induced FOXO1 transcriptional activation. Silencing of FOXO1 abrogated Trx1-induced drug resistance. Trx1 increased FOXO1-induced drug resistance, while Trx1 C69S mutant completely abolished the regulation of FOXO1-mediated drug resistance by Trx1. These findings provided a novel mechanism on Trx1/FOXO1 signaling in drug resistance in ovarian cancer cells.