Tumor Inhibition Ratio Research Articles

Structural characterization and anti-tumor activity of polysaccharide produced by Hirsutella sinensis

HSP-III, a novel homogeneous polysaccharide with 513.89kDa molecular weight, was fractionated from submerged cultures of Hirsutella sinensis by Sevag and chromatography on Sephadex G-100 column. The total sugar content of HSP-III was amounted to 89.87%. Based on the results of high performance gel permeation chromatogram (HPGPC), FT-IR, NMR spectroscopy, GC, periodate oxidation-smith degradation and methylation analysis, it showed that HSP-III was mainly composed of mannose and galactose, and a small amount of rhamnose, arabinose, xylose, and glucose. The molar ratio of Rha:Ara:Xyl:Man:Glu:Gal was 1.00:2.44:13.11:74.13:13.80:54.39. The main chain of HSP-III was majorly composed of (1→3) glucose. The tumor inhibition ratio on H22 cell was 79.04% at 100μg/mL of HSP-III.

Physicochemical Characterization and Antitumor Activity of Water-Soluble Polysaccharides from Bupleurum chinense

Bupleurum chinense belongs to the genus Bupleurum spp. and is one of the most important plant medicines in China used for over a thousand years. B. chinense is widely distributed in the northern region of China and is customarily called “Bei chaihu.” The clinical practice from ancient plant pharmacy experts showed that B. chinense possesses many pharmacological functions, such as balancing different organs and energies within the body, strengthening the action of the digestive tract, improving liver and circulatory system function, and relieving liver tension. In addition, contemporary pharmacological research indicated that B. chinense can effectively inhibit hepatoma and protect and promote hepatocyte regeneration. However, the active ingredients in B. chinense and possible mechanisms of its antihepatoma action are still unclear. The crude polysaccharide from the roots of Bupleurum chinense was extracted by hot water and ethanol precipitation with a yield of 12.4%. After deproteination by a combination of proteinase and the Sevag method, the supernatant was collected, dialyzed, and lyophilized to obtain water-soluble B. chinense polysaccharides (BCPs) 1 . BCPs appeared as a pale yellow powder and had a negative response to the Bradford assay 2 . In addition, no absorption at either 280 or 260 nm was detected by UV spectrophotometer, which indicated the absence of protein and nucleic acid. Results from phenol–sulfuric acid assay showed that BCPs contained 93.7% carbohydrate 3 and 5.4% uronic acid 4 . According to GC analysis, BCPs are composed of mannose, galactose, glucose, and galacturonic acid with the molar ratio 25:7.4:10:6.7 5 . We tested in vitro growth inhibition and cytotoxicity of BCPs against three tumor cell lines and two nontumorous cell lines. BCPs exhibited a significant cytotoxicity against H22 with the IC50 value of 103.3 g/mL. The IC50 values against B16 and S-180 were 289.3 and 371.2 g/mL, which showed that the inhibition effects of BCPs against B16 and S-180 were significantly lower than that against H22. The above results demonstrated that BCPs could specifically inhibit proliferation of tumor cells and had a discriminate antiproliferative activity against different types of tumor cells. In addition, BCPs exhibited extremely lower cytotoxicity to mouse embryonic fibroblast cell (NIH 3T3) and mouse macrophage cell (RAW 264.7) with high IC50 values over 1700 g/mL, implying that BCPs had no direct cytotoxicity to noncancerous cells and was safer than other chemotherapeutic drugs, having no negative side effects in inhibiting proliferation of nontumorous cells. We further evaluated the in vivo antitumor activity of BCPs on H22 solid tumor-bearing mice. Due to the fast growth of H22 tumor cells, the transplanted tumor model mice gradually exhibited a series of weakness symptoms such as loss of appetite and reduced body weight with dull hairs. After oral treatment with BCPs (50, 100, and 200 mg/kg), the growth of H22 tumors in the model mice was significantly suppressed compared with the negative control group (p < 0.05), and the tumor inhibition ratios were 22.7, 35.1, and 51.1% at concentrations of 50, 100, and 200 mg/kg body weight, respectively. Furthermore, the body weights of the BCP-treated group were increased significantly when compared with the negative control group and the CTX-treated group during the 15-day experimental period (data not shown).

Oral delivery of shRNA based on amino acid modified chitosan for improved antitumor efficacy

In this investigation, chitosan–histidine–cysteine (CHC) was engineered for oral delivery of Survivin short hairpin RNA (shRNA)-expressing plasmid DNA (shSur-pDNA) to promote hepatoma regression through integrating the advantages of histidine and cysteine to conquer serial cellular and systemic barriers. CHC could effectively encapsulate shSur-pDNA to form compact nanocomplexes (NC) at adequate weight ratios. Sequential modification with histidine and cysteine conferred CHC NC with the beneficial attributes for shRNA delivery including improved stability, facilitated internalization, promoted endosomal escape, increased nuclear localization, and GSH-responsive release, which contributed to their superior performance in terms of apoptosis promotion, proliferation inhibition, and Survivin down-regulation of tumor cells. More importantly, in hepatoma-bearing mice, orally delivered CHC NC overweighed chitosan counterparts with respect to suppressed Survivin expression, retarded tumor growth, and prolonged surviving time, owing to their above-mentioned merits in combination with enhanced intestinal permeation. Especially, rapid intracellular release of CHC NC with lower molecular weight of 30 kDa (CHC30 NC) might be responsible for the most satisfactory antitumor efficacy with tumor inhibition ratio (TIR) of 92.5%, which rendered CHC30 NC a promising vehicle for oral delivery of shRNA. This investigation would shed light on the deliberate design of oral shRNA delivery vehicles to mediate effective antitumor efficacy.

Design, synthesis and antitumor activity of triterpenoid pyrazine derivatives from 23-hydroxybetulinic acid

Pyrazine-fused 23-hydroxybetulinic acid was synthesized by introducing a pyrazine ring between C-2 and C-3 position and further modifications were carried out by substitution of C-28 carboxyl group by ester and amide linkage to enhance the antitumor activity. The biological screening results showed that all of the derivatives exhibited more significant antiproliferative activity than the parent compound. In particular compound 12a exhibited the most potent activity with IC50 values of 3.53 μM, 4.42 μM and 5.13 μM against cell lines SF-763, B16 and Hela, respectively. In the preliminary mechanism study, 12a caused cell arrest in G1 phase and significantly induced apoptosis of B16 cells in a dose-dependent manner. Furthermore, the in vivo antitumor activity of 12a was validated (tumor inhibitory ratio of 55.6% and 62.7%, respectively) in mice with H22 liver cancer and B16 melanoma.

Photo-Responsive and NGR-Mediated Multifunctional Nanostructured Lipid Carrier for Tumor-Specific Therapy

A novel nanostructured lipid carrier (NLC) modified with photon-sensitive cell penetrating peptides (psCPP) and Asn-Gly-Arg (NGR) was designed to enhance paclitaxel (PTX)-targeted delivery and antitumor effect. The NGR moiety selectively binds to CD13-positive tumors. On other hand, the psCPP moiety enhance specific cancer cellular uptake after rapidly cleaving the two-photon excitation-responsive protective group, in this case, illumination in the presence of near-IR (NIR) light at the tumor site. The dual-modified NLC (psCPP/NGR-NLC) were prepared by emulsification method, and the concentrations of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol 2000-psCPP (DSPE-PEG2000 -psCPP) and DSPE-PEG5000 -NGR in the NLC were chosen to be 4% and 1% (molar ratio), respectively. The mean particle size of the psCPP/NGR-NLC was about 100 nm, and the drug entrapment efficiency was more than 90%. Stability study showed that the prepared NLCs were physically and chemically stable at 2°C-8°C up to 1 month. Cellular uptake results demonstrated that the proposed psCPP/NGR-NLC had an enhancement of cancer cell recognition and specific uptake. Pharmacokinetic study showed that the prepared psCPP/NGR-NLC possessed the long-circulation characteristic with the t1/2 of 6.112 ± 0.304 h. Pharmacodynamics results confirmed that, with the aid of NIR illumination and NGR, the tumor inhibition ratio of psCPP/NGR-NLC group was significantly higher than the other PTX groups.

Antitumor Efficacy and Mechanism in Hepatoma H22-Bearing Mice of Brucea javanica Oil.

Brucea javanica is a traditional herbal medicine in China, and its antitumor activities are of research interest. Brucea javanica oil, extracted with ether and refined with 10% ethyl alcohol from Brucea javanica seed, was used to treat hepatoma H22-bearing mice in this study. The antitumor effect and probable mechanisms of the extracted Brucea javanica oil were studied in H22-bearing mice by WBC count, GOT, GPT levels, and western blotting. The H22 tumor inhibition ratio of 0.5, 1, and 1.5 g/kg bw Brucea javanica oil were 15.64%, 23.87%, and 38.27%. Brucea javanica oil could inhibit the involution of thymus induced by H22 tumor-bearing, but it could not inhibit the augmentation of spleen and liver. Brucea javanica oil could decrease the levels of WBC count and GOT and GPT in H22-bearing mice. The protein levels of GAPDH, Akt, TGF-β1, and α-SMA in tumor tissues decreased after being treated with Brucea javanica oil. Disturbing energy metabolism and neoplastic hyperplasia controlled by Akt and immunoregulation activity were its probable antitumor mechanisms in hepatoma H22-bearing mice.

Effects of Ciji Hua'ai Baosheng granule formula (CHBGF) on life time, pathology, peripheral blood cells of tumor chemotherapy model mouse with H22 hepatoma carcinoma cells.

Ciji Hua'ai Baosheng Granule Formula (CHBGF) is a traditional Chinese empirical formula that can help the tumor patients who have received chemotherapy antagonize the toxin and side-effects so as to improve and prolong the life. This study is to evaluate the effects of CHBGF on improving life quality in terms of survival time, pathology of tumor tissue and ameliorating peripheral blood cells in mouse chemotherapy model with subcutaneous transplanted tumor or ascitic tumor of H22 hepatoma carcinoma cells at an overall level. 71 mice among the 92 Kunming mice were injected subcutaneously into the right anterior armpit with H22 hepatoma carcinoma cells, after 7 days, which had formed tumors and were used peritoneal injection of Cytoxan (CTX) (200mg/kg) to establish the mouse chemotherapy model with transplanted tumor, and then which were commensurately divided into 8 groups by random digits table. 21 mice were injected into peritoneal cavity to use CTX and the same method to establish the model. The groups for evaluating the effects on the survival time were the model, CHBGF and positive control group respectively with 7 mice in each group. The groups for evaluating the effects on anti-cancer were the model group, three treatment groups and positive control group with 10 mice in each group. The survival-time-observing groups were given intragastric administration of normal saline, CHBGF (64g/kg) once a day, and peritoneal injection of 5-Fluorouracil (25mg/kg) once every other day respectively. The survival time of each group was observed. The five anti-cancer-observing groups were given intragastric administration of normal saline, CHBGF (64g/kg, 32g/kg and 16g/kg) once a day, and peritoneal injection of 5-Fluorouracil (25mg/kg) once every other day respectively. After treatment for 21 days, the transplanted tumors were peeled off. Blood was collected through pricking eyeball and analyzed by hematology analyzer. And postchemotherapy transplanted tumor inhibition ratios were calculated. Pathological changes of tumor tissues and blood smears were observed with light microscope. The life prolonging rate of CHBGF (64g/kg) group with transplanted tumor is 20.14%, and their survival time was longer than that of the 5-Fluorouracil group (P<0.05). Life prolonging rate of CHBGF (64g/kg) group with ascitic tumor is 64.15%, the survival time was longer than that of the model group (P<0.01) and the 5-Fluorouracil group (P<0.05). The growth of the transplanted tumor in model group was faster than that in CHBGF (64g/kg) group and 5-Fluorouracil group (P<0.05). The tumor average weight of the positive drug and the CHBGF (64g/kg, 32g/kg) groups was lighter than that of the model group (P<0.05 or P<0.01). The inhibition ratios of CHBGF (64g/kg, 32g/kg and 16g/kg) groups are 31.15%, 21.31%, and 13.11% respectively. Under light microscope, in the positive drug and three CHBGF groups the pathological deteriorated severity of tumor tissue observed was milder than that in the model group, the distribution of WBC in CHBGF groups was more obvious than that of the model and 5-Fluorouracil groups. The WBC and PLT decrease in CHBGF (64g/kg, 32g/kg and 16g/kg) groups is less than the model and the 5-Fluorouracil group (P<0.05 or P<0.01), the number of RBC and HGB just in the CHBGF (64g/kg) group was more than that of the model group or the 5-Fluorouracil group (P<0.05). Ciji Hua'ai Baosheng Granule Formula can prolong the survival time of the mice chemotherapy model of both subcutaneous transplanted tumor and ascitic tumor of H22 hepatoma carcinoma cells, has some determinate inhibitory effects on the growth of subcutaneous transplanted tumor chemo-treated, and has the therapeutic effect on antagonizing decrease of WBC and PLT caused by chemotherapy.

The application of EDTA in drug delivery systems: doxorubicin liposomes loaded via NH4EDTA gradient

The applications of ethylenediaminetetraacetic acid (EDTA) have been expanded from the treatment of heavy metal poisoning to chelation therapies for atherosclerosis, heart disease, and cancers, in which EDTA reduces morbidity and mortality by chelating toxic metal ions. In this study, EDTA was used in a drug delivery system by adopting an NH4EDTA gradient method to load doxorubicin into liposomes with the goal of increasing therapeutic effects and decreasing drug-related cytotoxicity. The particle size of the optimum NH4EDTA gradient liposomes was 79.4±1.87 nm, and the entrapment efficiency was 95.54%±0.59%. In vitro studies revealed that liposomes prepared using an NH4EDTA gradient possessed long-term stability and delayed drug release. The in vivo studies also showed the superiority of the new doxorubicin formulation. Compared with an equivalent drug dose (5 mg/kg) prepared by (NH4)2SO4 gradient, NH4EDTA gradient liposomes showed no significant differences in tumor inhibition ratio, but cardiotoxicity and liposome-related immune organ damage were lower, and no drug-related deaths were observed. These results show that use of the NH4EDTA gradient method to load doxorubicin into liposomes could significantly reduce drug toxicity without influencing antitumor activity.

Preparation, Characterization, and Pharmacodynamics of Thermosensitive Liposomes Containing Docetaxel

A novel thermosensitive liposome (TL) containing docetaxel (DTX) was designed to enhance DTX-targeted delivery and antitumor effect. TL loading DTX (DTX-TL) were prepared by thin film hydration. The mean particle size of the liposomes was about 100 nm, and the drug entrapment efficiency was more than 95%. The phase transition temperature of liposomes was about 42 °C. In vitro drug release showed that drug released at 37 °C was obviously less than that at 42 °C. For in vivo experiments, the human breast tumor model was established by subcutaneous xenotransplantation on nude mice; liposomes and injection containing DTX were injected i.v. in nude mice, followed by exposure of the tumors to hyperthermia (HT) for 30 min after administration. The tumor inhibition ratio of DTX-TL group was significantly higher than the normal injection group. Combining TL with HT enhanced the delivery of DTX and thereby its antitumor effects. The liposomes reported in this paper could potentially produce viable clinical strategies for improved targeting and delivery of DTX for the treatment of breast cancer.

An upconversion nanoparticle – Zinc phthalocyanine based nanophotosensitizer for photodynamic therapy

Recent advances in NIR triggering upconversion-based photodynamic therapy have led to substantial improvements in upconversion-based nanophotosensitizers. How to obtain the high efficiency of singlet oxygen generation under low 980 nm radiation dosage still remains a challenge. A highly efficient nanophotosensitizer, denoted as UCNPs-ZnPc, was constructed for photodynamic therapy, which is based on near infrared (NIR) light upconversion nanoparticle (UCNP) and Zn(II)-phthalocyanine (ZnPc) photosensitizer (PS). The high 1O2 production efficiency came from the enhancement of the 660 nm upconversion emission of NaYF4:Yb3+, Er3+ UCNP with 25% Yb3+ doping, covalent assemblage of UCNP and ZnPc which significantly shortened the distance and enhanced the energy transfer between the two. The high 1O2 production led to a secure and efficient PDT treatment, as evidenced by the in vivo test where UCNPs-ZnPc of 50 mg per kg body weight was locally injected into the liver tumor in mice, a low 980 nm radiation dose of 351 J/cm2 (0.39 W/cm2) and short irradiation duration of 15 min were sufficient to perform image-guided PDT and caused the liver tumor inhibitory ratio of approximately 80.1%. Histological analysis revealed no pathological changes and inflammatory response in heart, lung, kidney, liver or spleen.

Dynamic disordering of liposomal cocktails and the spatio-temporal favorable release of cargoes to circumvent drug resistance

Multidrug resistance (MDR) has been a major impediment to the success of cancer chemotherapy. Extensive efforts have been devoted to the development of drug delivery systems using nanotechnology to reverse MDR in cancer. However, the spontaneous release of drug payloads was always a slow process, which leads to the low intracellular drug concentration resulting in consequent drug insensitivity. To circumvent this limitation, we described a liposomal cocktail (LMDHV) constructed by a pH-responsive molecule (i.e., malachite green carbinol base (MG)) and liposome conjugated with Her-2 antibody for codelivery of doxorubicin (DOX) and verapamil (VER) to suppress drug resistance in Her-2 positive breast cancer. MG inserted in the bilayer as pH responders greatly contributed to the destabilization of the vesicle membrane in low pH, followed by the rapid release of the payloads. LMDHV showed 6-fold reversal efficiency in DOX resistant breast cancer owing to the efficient tumor targeting delivery and rapid burst release of drug intracellularly. Compared to tumor inhibition ratio of treated groups by free DOX (32.4 ± 7.4%), our designed kinetically favorable drug release system exhibited significantly (P < 0.01) enhanced tumor inhibition ratio up to 83.9 ± 12.5%, which is attributed to the remarkably increased drug concentration in cells. The spatio-temporal favorable release of drugs resulted in synergistic inhibition of tumor growth in xenografts. We envision that this new type of liposomal cocktail might be potentially utilized to circumvent drug resistance in the future.

A wogonin-loaded glycyrrhetinic acid-modified liposome for hepatic targeting with anti-tumor effects

Liver cancer has become one of the most common fatal cancers worldwide, with morbidity rates increasing each year. Wogonin (WG) is an attractive candidate for the development of new anti-cancer drugs. In this study, a novel glycyrrhetinic acid (GA)-modified WG liposome was developed for use in targeted anti-cancer therapy. Three types of WG preparations were investigated: free wogonin in solution (WG), passively targeted wogonin liposomes (WG-Lip) and GA-modified wogonin liposomes (GA-WG-Lip). The entrapment efficiency, size and zeta potential were measured. Cellular uptake, cytotoxicity, in vivo bio-distribution and anti-tumor efficacy were also investigated. Addition of GA to the liposomes did not diminish the high entrapment efficiency observed in the liposomes without GA. GA-WG-Lip showed the greatest uptake and had an IC50 value 1.46 times higher than that of WG-Lip. The GA-modified liposomes rapidly accumulated in the liver with a long retention time, and also displayed a better tumor inhibitory ratio than that of the unmodified liposomes. Overall, the data indicated that use of the GA-modified WG liposomes conferred improvements in bio-distribution, accumulation at the tumor and therapeutic efficacy, perhaps due to increased receptor-mediated uptake of liposomes by liver-targeted cells. Together, these data show that GA-WG-Lip is a promising means of targeted therapy for liver cancer.

Sonodynamic antitumor effect of a novel sonosensitizer on S180 solid tumor

The purpose of this study was to evaluate the sonodynamically induced antitumor effect of a novel sonosensitizer (DVDMS) in mice bearing sarcoma 180 solid tumors. In order to determine the optimum timing of ultrasound exposure after administration of DVDMS, a three-dimensional optical imaging system (IVIS spectrum) was used to observe the biodistribution of DVDMS in S180 tumor. The antitumor effects were estimated by the tumor inhibition ratio (volume and weight) after sonodynamic therapy. The experiments suggested that DVDMS has a preferential localization in tumors, but a low accumulation in most normal tissues. A significant synergistic effect of ultrasound combined with DVDMS was obtained when the load power indicated 4 W and DVDMS dose was above 2 mg/kg. At day 14 after DVDMS-SDT, the tumor volume inhibition ratio was 56.27%. In addition, the tumor weight inhibition ratio after the synergistic treatment was 55.37%, which was obviously stronger than ultrasound treatment alone (23.85%) and DVDMS alone (23.15%). Moreover, no metastasis occurred to the tumors in the SDT-treated mice compared with the control group. DVDMS is a potential sensitizer for sonodynamic cancer therapy. The antitumor effect of ultrasound could be enhanced in the presence of DVDMS, which might be involved in a sonochemical mechanism.

Transferrin-modified Doxorubicin-loaded biodegradable nanoparticles exhibit enhanced efficacy in treating brain glioma-bearing rats.

Doxorubicin (Dox) is widely used for the treatment of solid tumors but its clinical utility on glioma is limited. In this study, we developed a novel nano-scale drug delivery system employing biodegradable nanoparticle (NP) as carriers to load Dox. Transferrin (Tf) was conjugated to the surface of NP to specifically target the NP to glioma. Tf-NP-Dox was prepared via emulsification-solvent evaporation method, and characterized for the size, Drug loading capacity (DLC), entrapment efficiency, and Tf number on the surface. The antitumor efficiency in vitro was evaluated via CCK-8 assay. The transmembrane transportation was evaluated via HPLC assay. The antitumor efficiency in vivo was assessed in C6 glioma intracranial implant rat model. The average diameter of Tf-NP-Dox was 100 nm with ∼32 Tf molecules on the surface. DLC was 4.4%. CCK-8 assay demonstrated much stronger cytotoxicity of Tf-NP-Dox to C6 glioma cells compared to NP-Dox or Dox. HPLC assay showed that Tf-NP-Dox transported Dox into C6 cells with high efficiency. In vivo, Tf-NP-Dox could transport Dox into tumors compare to contralateral part, with tumor inhibitory ratio and survival higher than NP-Dox or Dox. Taken together, our results suggest that Tf-NP-Dox exhibits better therapeutic effects against glioma both in vitro and in vivo, and is a potential nano-scale drug delivery system for glioma chemotherapy.

Anticancer Effect of dl-Glyceraldehyde and 2-Deoxyglucose in Ehrlich Ascites Carcinoma Bearing Mice and Their Effect on Liver, Kidney and Haematological Parameters.

Cancer cells generally exhibit increased glycolysis for ATP generation (the Warburg effect). Compounds that inhibit glycolysis have potential applications in cancer treatment. dl-glyceraldehyde (DLG) and 2-Deoxyglucose (2-DG) have been proven effective in the inhibition of glucose metabolism. Ehrlich ascites carcinoma (EAC) cells were injected intraperitoneally (i.p) in 10-12weeks old Swiss albino mice, weighing between 20 and 30g. The anticancer activity of DLG and 2-DG were determined by tumor volume, tumor weight, viable and nonviable tumor cell count, average survival time, percentage increase in life span and tumor inhibition ratio. The blood samples were obtained for biochemical analysis after 9days of treatment to study the effect on liver, kidney and haematological parameters. Histopathological examination of liver and kidney was also performed. One-way ANOVA test and Dunnett's test were used for comparisons of parameters in study groups. Both DLG and 2-DG individually decreased the tumor weight, tumor volume, viable tumor cell count and significantly increased the life span of treated mice, however the combination was found to be better. The biochemical parameters of liver and kidney functions and haematological parameters were restored close to control group as compared with the EAC bearing mice. Histopathological examination of liver and kidney in EAC control group showed large areas of necrosis, congestion and mononuclear cell infiltration but such changes were not observed in liver and kidney sections observed after i.p injection of DLG and 2-DG for 9days. Improvement was much better in the group where combination of these two drugs were used.

Antitumor activity of hyaluronic acid–selenium nanoparticles in Heps tumor mice models

In this study, hyaluronic acid–selenium (HA–Se) nanoparticles as novel complexes were synthesized and their antitumor activities in vivo were investigated. The mice inoculated with Heps tumor were orally administered with HA–Se nanoparticles at 86.45mg/kg (H) and 4.32mg/kg (L) body weights as high and low doses respectively (2.20% selenium content in the HA–Se nanoparticles samples by ICP-AES) for 10 days. The transmission electron microscopy (TEM) results indicated that the HA–Se nanoparticles were spherical with mean size of 50–70nm. The HA–Se nanoparticles could significantly reduce tumor weights at the tumor inhibition ratios of 46.92% (H) and 49.12% (L) respectively. However, in the 5-fluorouracil positive group (25mg/kg), the tumor inhibition ratio was 61.71%. From the study, the HA–Se nanoparticles (4.32mg/kg) significantly increased thymus and spleen relative weights, enhanced the activities of superoxide dismutase (SOD), reduced the formation of malondialdehyde (MDA) and the activities of aspartate transaminase, alanine transaminase and crea in Heps tumor mice. The results of the study indicated that the HA–Se nanoparticles are potential antitumor candidate for cancer treatment.

Anti-bacterial and in vivo tumor treatment by reactive oxygen species generated by magnetic nanoparticles.

Photodynamic therapy is widely used in clinics and for anti-bacterial applications. The major challenge is the limited depth of tissue penetration of light and poor targetability. In this study, magnetite nanoparticles were used as a highly sensitive T2-weighted MR imaging contrast agents to target the tumor and mimic horseradish peroxidase (HRP), which could catalyze the decomposition of hydrogen peroxide to generate reactive oxygen species (ROS) to inhibit the tumor in vivo. In these experiments, MNPs were demonstrated to possess the enzyme-mimicking activity in different pH values, and the activity was dependent on the size of the MNPs: the smaller the size, the higher the activity. We demonstrated that MNPs showed highly efficient anti-bacterial (E. coli) activity in presence of H2O2. The E. coli inhibition ratio reached nearly 100% at optimal concentration. The anti-tumor activity was evaluated through HeLa cell viability under treatment with MNPs and H2O2. Consequently, the cell viability was significantly decreased and more than 80% of HeLa cells were dead after treatment with MNPs and H2O2 under different pH values. MR imaging was used to demonstrate the tumor targetability of 13 nm MNPs in vitro and in vivo. Consequently, the relaxivity of the 13 nm MNPs was determined to be r2 = 104 s-1 mM-1. The MR signal was much more negative and the intensity was significantly diminished with the increase of the concentration of 13 nm MNPs in vitro. The tumor signal was clearly visualized and a 3-fold decrease of the MR signal intensity of the tumor site of the mice was observed after 24 h-post treatment with the 13 nm MNPs. Finally, the tumor inhibition in vivo was investigated using 6 nm MNPs in BALB/c nude female mice bearing subcutaneously implanted HeLa cells on the right flank. The results show statistically significant efficacy in delaying tumor growth from day 6, and an approximately 99% tumor inhibition ratio was shown by the combination of MNPs and H2O2 after treatment for 17 days. By leveraging the passive targeting and MR imaging properties, we expect that the enzyme-mimicking MNPs could be used for cancer theranostics and may open up a new avenue for the treatment of epidermal infections.

In Vivo Targeted Deep-Tissue Photodynamic Therapy Based on Near-Infrared Light Triggered Upconversion Nanoconstruct

Two major challenges of current photodynamic therapy (PDT) are the limited tissue penetration of excitation light and poor tumor-selectivity of the photosensitizer (PS). To address these issues, we developed a multifunctional nanoconstruct consisting of upconversion nanoparticles (UCNPs) that transform near-infrared (NIR) light to visible light and a photosensitizer zinc(II) phthalocyanine (ZnPc). Folate-modified amphiphilic chitosan (FASOC) was coated on the surface of UCNPs to anchor the ZnPc close to the UCNPs, thereby facilitating resonance energy transfer from UCNPs to ZnPc. Confocal microscopy and NIR small animal imaging demonstrated the enhanced tumor-selectivity of the nanoconstructs to cancer cells that overexpressed folate receptor. Reactive oxygen species (ROS) generation in cancer cells under a 1-cm tissue was higher upon excitation of UCNPs with the 980 nm light than that with 660 nm irradiation. In vivo PDT treatments for deep-seated tumors demonstrated that NIR light-triggered PDT based on the nanoconstructs possessed remarkable therapeutic efficacy with tumor inhibition ratio up to 50% compared with conventional visible light-activated PDT with a noticeable reduced tumor inhibition ratio of 18%. These results indicate that the multifunctional nanoconstruct is a promising PDT agent for deep-seated tumor treatment and demonstrate a new paradigm for enhancing PDT efficacy.

Preparation, In Vitro, and In Vivo Antitumor Activity of Folate Receptor‐Targeted Nanoliposomes Containing Oridonin

Abstract Preclinical Research The expression of the folate receptor (FR) is amplified in many cancer types. Oridonin (ORI, C20H28O6) is an isolate from Rabdosia rubescens (Hemsl.) Hara that has been used in the treatment of esophageal and hepatic carcinoma for decades. In order to enhance the antitumor potency of ORI, folate‐polyethylene glycol2000‐distearoylphosphatidyleth‐anolamine (folate‐PEG2000‐DSPE) was synthesized to facilitate preparation of FR‐targeted liposomal ORI (F‐L‐ORI). F‐L‐ORI and PEG2000‐DSPE‐L‐ORI were then prepared. In vitro release properties, cellular uptake, and cytotoxicity in HepG‐2 cells, as well as in vivo potency of the liposomes in murine HepG‐2 tumor‐bearing mice were evaluated. An in vitro cytotoxicity assay on F‐L‐ORI gave an IC50 value of 0.718 ± 0.023 μmol/ml and L‐ORI had an IC50 value of 2.25 ± 0.12 μmol/ml. These liposomes were able to control the release of ORI. In vitro cells binding of F‐L‐ORI exhibited higher binding to HepG‐2 cells as compared with L‐ORI. The antitumor effect studies assessed in vivo showed that F‐L‐ORI improved the antitumor activity of ORI as compared with L‐ORI and free drug. The tumor inhibition ratio for F‐L‐ORI (1.5 × 10−2 g/kg/d) was 85.6%, higher than that of L‐ORI group (1.5 × 10−2 g/kg/d) and free ORI (1.5 × 10−2 g/kg/d) that were 66.8% and 40.8%, respectively.

Sulfated modification of the polysaccharide from Cordyceps_gunnii mycelia and its biological activities

A chemically new sulfated polysaccharide (SPS50) was prepared from the water soluble polysaccharide (PS50), isolated from Cordyceps_gunnii mycelia, by concentrated sulfuric acid method. The yield of crude SPS50 was 62.34% and its specific rotation was [α]D20=−36.75°. The structural characteristics of this chemically sulfated polysaccharide were determined based on the infrared analysis (IR), high performance liquid chromatography (HPLC) and sodium dodecyl sulfate polyacrylamide gel electropheresis (SDS-PAGE). Its biological properties including anti-oxidant and anti-tumor activities were also investigated. The results showed that the anti-oxidant capacity of SPS50 was not as good as SP50 and the anti-tumor activity of SPS50 was much better than PS50. SPS50 showed evident growth inhibition on K562 cells. The tumor inhibition ratio of SPS50 against K562 cells was 69.92%.