Correction: Tumor-targeting, enzyme-activated nanoparticles for simultaneous cancer diagnosis and photodynamic therapy.

Correction for 'Tumor-targeting, enzyme-activated nanoparticles for simultaneous cancer diagnosis and photodynamic therapy' by Huaxia Shi et al., J. Mater. Chem. B, 2016, 4, 113-120, https://doi.org/10.1039/C5TB02041G.

Transient receptor potential channels in multiple myeloma.

Multiple myeloma is the second most commonly diagnosed hematologic malignancy. As an incurable disease, the molecular mechanisms underlying its many aspects remain unclear. Intracellular calcium ion is an essential signaling molecule that modulates malignant cell behavior, and abnormal regulation of cellular calcium homeostasis may promote cancer cell survival and induce drug resistance. Transient receptor potential (TRP) cation channels are a superfamily of non-selective Ca2+-permeable channels that regulate intracellular calcium signaling and are involved in the regulation of various characteristics of cancer cells. Emerging evidence shows a close connection between TRP channels and multiple myeloma. This review summarizes the roles of TRP channels in multiple myeloma progression, metastasis, bone destruction, and drug resistance. TRPV1 and TRPV2 orchestrate the progression of multiple myeloma, while TRPM7 promotes myeloma cell dissemination and spreading. TRPV2 and TRPV4, that activate osteoclasts, contribute to the development of osteolytic bone disease caused by multiple myeloma. Both TRPV1 inhibition and TRPV2 activation synergize with bortezomib in the chemotherapy of multiple myeloma, and TRPC1 can determine the responsiveness of multiple myeloma to MTI-101, a cyclic beta-hairpin peptide. Antagonizing TRPA1 can alleviate bortezomib-induced painful peripheral neuropathy. Future studies in this field may identify certain TRP channels as markers or therapeutic targets for predicting the prognosis, preventing progression, and improving drug responsiveness in patients with multiple myeloma.

HOXA11-AS promotes the migration and invasion of hepatocellular carcinoma cells by inhibiting miR-124 expression by binding to EZH2.

The objective of this study was to examine the function of the long non-coding RNA (lncRNA) HOXA11-AS in hepatocellular carcinoma (HCC). In total, samples from liver tumor and surrounding normal liver tissues were collected from 66 cases of HCC patients. Normal liver cell line HL-7702 and HCC cell lines HepG2, Hep3B, MHCC-97H and BEL7402 were used. Cells were transfected with different small interference RNAs or vectors. Then, transwell assay, qRT-PCR, CHIP, RIP and Western blot experiments were performed. We found that the HOXA11-AS expression level was higher in HCC samples than surrounding normal liver tissues. And the higher expression level of HOXA11-AS in HCC patients indicated a lower 5-year survival rate. Knockdown of HOXA11-AS in HepG2 and Hep3B cells caused impaired cell invasion and migration abilities. Otherwise, upregulation of HOXA11-AS in MHCC-97H and BEL7402 cells displayed higher invasion and migration capabilities. We also demonstrated that HOXA11-AS could inhibit miR-124 expression by binding to EZH2. Furthermore, overexpression of miR-124 or knockdown EZH2 expression could reverse the HOXA11-AS-induced migration and invasion effects in HCC cells. In summary, the high HOXA11-AS expression in HCC patients is associated with the poor outcome. HOXA11-AS could inhibit miR-124 expression by binding to EZH2 and thus promoted the migration and invasion of HCC cells.

Investigation of the cytotoxicity, apoptosis and pharmacokinetics of Raddeanin A.

Raddeanin A, one of the triterpenoid saponins extracted from Anemone raddeana rhizome of the Ranunculaceae family, has demonstrated the ability to inhibit the growth of human hepatic and gastric cancer cells. However, the effects of Raddeanin A on human colon cancer cells have not been investigated extensively. The present study aimed to examine the antiproliferative and apoptosis-inducing effects of Raddeanin A on the HCT-116 human colon cancer cell line in vitro, and evaluate the pharmacokinetic and biodistribution properties of Raddeanin A in mice following a single oral administration. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to assess the in vitro cytotoxicity of Raddeanin A against HCT-116 cells. 4',6-Diamidino-2-phenylindole, dihydrochloride staining and flow cytometry were performed to further examine the apoptosis-inducing capability of Raddeanin A. The concentrations of Raddeanin A in the plasma and tissues were analyzed using liquid chromatography-tandem mass spectrometry. Raddeanin A showed a dose-dependent antiproliferative effect towards the HCT-116 cells, with a half maximal inhibitory concentration of ~1.4 µM. Treatment with Raddeanin A resulted in a significant induction of apoptosis, observed as apparent morphological changes of the nuclei, with a total apoptotic ratio of 41.8% at a concentration of 3 µM. Low concentrations of Raddeanin A were detected in the heart, liver, spleen, lung, kidney and plasma of the mice following oral administration, however, the majority of the Raddeanin A was distributed in the intestinal tract, particularly in the colon and caecum. These present study confirmed the growth-inhibitory and apoptosis-inducing effects of Raddeanin A on HCT-116 cells and performed preliminary examinations of its pharmacokinetic properties, which provide a foundation for further investigating the inhibitory mechanism on the colon cancer cells in vivo.

Wnt/ß-catenin signaling plays an important role in the protective effects of FDP-Sr against oxidative stress induced apoptosis in MC3T3-E1 cell.

Strontium fructose 1,6-diphosphate (FDP-Sr) is a new strontium-containing compound. The primary aim of this study was to clarify whether the structure component of FDP-Sr, FDP could benefit the protective effect of Sr (II) against oxidative stress induced apoptosis, and meanwhile to further explore the important role of Wnt/ß-catenin signaling in the anti-apoptosis effect of FDP-Sr in response to oxidative stress induced by H2O2 in an osteoblastic MC3T3-E1 cell line. Results showed that FDP-Sr could improve the osteoblastic differentiation under oxidative stress with induced cell proliferation and improved mineralization. The inhibition effect of FDP-Sr on cell apoptosis induced by H2O2 was proved by reduced reactive oxygen species production and activated caspase3. Under oxidative stress, mRNA and protein levels of phospho-ß-catenin reduced, while ß-catenin increased in the FDP-Sr treatment cell, leaded to the up-regulations of Runx2 and OPG at both mRNA and protein levels, finally improved the differentiation of osteoblasts. By the engagement of Wnt/ß-catenin pathway's inhibitor (XAV-939), the protective effects of FDP-Sr on osteoblastic differentiation against oxidative stress were repressed along with inhibited wnt/ß-catenin signaling and reduced mRNA and protein levels of Runx2 and OPG. In conclusion, FDP-Sr was demonstrated to protect osteoblast differentiation from oxidative damage induced by H2O2 through up-regulation of Wnt/ß-catenin signaling, and FDP in FDP-Sr was able to directly improve the oxidative stress injury through its ROS scavenging ability.

A Thienyl-Substituted Diketopyrrolopyrrole Derivative with Efficient Reactive Oxygen Species Generation for Photodynamic Therapy.

Reducing the energy gap of photosensitizer between singlet and triplet states (ΔEST ) can improve the efficiency of intersystem crossing, further enhancing the resulting generation of reactive oxygen species for photodynamic therapy. In this study, two photosensitizer chromophores-phenyl-substituted diketopyrrolopyrrole and thienyl-substituted diketopyrrolopyrrole (TDPP)-were synthesized. Theoretical calculations indicate that TDPP can greatly reduce the ΔEST (0.48 eV) relative to that of diketopyrrolopyrrole (0.66 eV). Experiments confirmed that TDPP generates reactive oxygen species more efficiently than diketopyrrolopyrrole. After conjugation of TDPP with methoxy poly(ethylene glycol)carboxyl (mPEG-COOH), the resulting TDPP-mPEG has excellent water solubility, biocompatibility and photostability. When it serves as photosensitizer for photodynamic therapy, in vitro and in vivo measurements indicate that TDPP-mPEG can effectively inhibit tumor growth and shows great potential for the treatment of cancer in the clinic.

Tumor-targeting, enzyme-activated nanoparticles for simultaneous cancer diagnosis and photodynamic therapy.

Specific targeting towards tumors and the on-site activation of photosensitizers to diagnose tumors and reduce side effects for patients are currently the main challenges for photodynamic therapy (PDT) in the clinic. Herein, uniform diiodostyryl bodipy conjugated hyaluronic acid nanoparticles (DBHA-NPs) were successfully synthesized. The evaluation of their PDT effect at both a cellular level and in animal models of tumor-bearing mice shows that the DBHA-NPs present a remarkable suppression of tumorous growth due to their specific targeting and enhanced permeability and retention (EPR) effect. More importantly, the enzyme-activated "self-assembly and disaggregation" behavior in tumors can lead to the on-site activation of DBHA-NPs, which can diagnose the tumor exactly and reduce the side effects for patients significantly. These findings confirm that DBHA-NPs have significant potential for photodynamically activated cancer theranostics in a clinical setting.

Simultaneous determination of osthole, bergapten and isopimpinellin in rat plasma and tissues by liquid chromatography-tandem mass spectrometry.

A highly selective and sensitive method for simultaneous quantitation of osthole, bergapten and isopimpinellin in rat plasma and tissues was developed by liquid chromatography-tandem quadrupole mass spectrometry (LC-MS/MS). After liquid-liquid extraction of samples with methyl tert-butyl ether, the analytes and dextrorphan (internal standard, IS) were separated by a Hypersil GOLD AQ C18 column with gradient elution of acetonitrile and water containing 0.5‰ formic acid. Three determinands were detected using an electrospray ionization (ESI) tandem mass spectrometry in the multiple reaction monitoring (MRM) modes with positive electrospray ionization. Calibration curves were recovered over the concentration ranges of 1-200 ng/ml, 1-500 ng/ml, 0.25-200 ng/ml for osthole, bergapten and isopimpinellin in plasma; 1-100 ng/ml, 1-500 ng/ml, 0.5-100 ng/ml for osthole, bergapten and isopimpinellin in tissues, respectively. The intra-day precision (R.S.D.) was within 13.90% and the intra-day accuracy (R.E.) was within -6.27 to 6.84% in all biological matrixes. The inter-day precision (R.S.D.) was less than 13.66% and the inter-day accuracy (R.E.) was within -10.64 to 13.04%. Then the method was successfully applied to investigate plasma pharmacokinetic study and tissue distribution of osthole, bergapten and isopimpinellin in rats after oral administration of Fructus Cnidii extraction, especially for testis/uterus tissue distribution. The results demonstrated that osthole, bergapten and isopimpinellin were absorbed and eliminated rapidly with wide distributions in rats. Distribution data of these three bioactive components in testis/uterus tissues could offer useful information for the further preclinical and clinical studies of Fructus Cnidii in the treatment of genital system disease.