Lower frequency of MDSCs was significantly related to functional cure in CHB patients treated with peginterferon.

BACKGROUND AND AIMS: Myeloid-derived suppressor cells (MDSCs) and CD4+ regulatory T cells (Tregs) expand during chronic hepatitis B virus (HBV) infection and inhibit antiviral immunity. However, the relationship between antiviral effect and the frequencies of those immune suppressive cells after pegylated interferon α-2a (PegIFNα-2a) therapy is not clearly understood. This study aimed to investigate the contribution of monocytic MDSCs (mMDSCs) and CD4+ Tregs to functional cure (HBsAg seroclearance) after PegIFNα-2a therapy and evaluate the effect of PegIFNα-2a therapy on these cells. METHODS: Flow cytometry analysis was performed along with longitudinal immune monitoring of 97 hepatitis B e antigen (HBeAg) negative chronic hepatitis B (CHB) patients receiving PegIFNα-2a weekly for 48 weeks. RESULTS: The frequencies of mMDSCs and CD4+ Tregs increased in all HBV patients, and they were higher in the HBsAg persistence group than in the HBsAg seroclearance group. A significant decline in the frequency of mMDSCs was found in patients who realized functional cure after PegIFNα-2a treatment. In contrast, the frequency of CD4+ Tregs in both the HBsAg seroclearance and persistence groups significantly increased. Multivariate analyses indicated that the baseline serum HBsAg levels (p < .001) and mMDSCs frequency (p = .027) were independently associated with the HBsAg clearance, and the combined marker (HBsAg plus mMDSCs) displayed the highest specificity (93.1%) than any other markers in predicting HBsAg seroclearance. CONCLUSIONS: These results suggest that a poor response to PegIFNα-2a treatment in CHB patients may be related to the frequencies of immune suppressive cells, while the therapeutic targeting of these cells might be effective in boosting anti-HBV immunity.

A Celastrol Drug Delivery System Based on PEG Derivatives: The Structural Effects of Nanocarriers.

The therapeutic efficacy of nanoscale drug delivery systems is related to particle size, zeta potential, morphology, and other physicochemical properties. The structure and composition of nanocarriers may affect their physicochemical properties. To systematically evaluate these characteristics, three analogues, namely polyethylene glycol (PEG), PEG-conjugated octadecylamine (PEG-C18), and tri(ethylene glycol) (TEG), were explored as nanocarriers to entrap celastrol (CSL) via the injection-combined dialysis method. CSL nanoparticles were successfully prepared as orange milky solutions, which revealed a similar particle size of approximately 120 nm, with narrow distribution and a negative zeta potential of -20 mV. All these CSL nanoparticles exhibited good storage stability and media stability but presented different drug-loading capacities (DLCs), release profiles, cytotoxicity, and hemolytic activity. For DLCs, PEG-C18/CSL exhibited better CSL entrapment capacity. Regarding the release profiles, TEG/CSL showed the lowest release rate, PEG-C18/CSL presented a moderate release rate, and PEG/CSL exhibited a relatively fast release rate. Based on the different release rates, PEG-C18/CSL and TEG/CSL showed higher degrees of cytotoxicity than PEG/CSL. Furthermore, TEG/CSL showed the lowest membrane toxicity, and its hemolytic rate was below 20%. These results suggest that the structural effects of nanocarriers can affect the interactions between nanocarriers and drugs, resulting in different release profiles and antitumor activity.

Thyroid dysfunction incidence and risk factors in Chinese chronic hepatitis B patients treated with pegylated interferon alpha: A long-term follow-up study.

The long-term impact, incidence and risk factors of thyroid dysfunction in chronic hepatitis B (CHB) patients receiving pegylated interferon (IFN) alpha (PegIFN-alpha) therapy remain unclear. We aim to investigate the long-term safety of thyroid dysfunction in CHB patients receiving PegIFN-alpha. A retrospective observational study of 425 CHB patients with normal baseline thyroid function was carried out. Patients were followed up over 10 years to assess thyroid function after receiving IFN. At the end of the IFN therapy, 67 patients (15.8%) had developed thyroid dysfunction, 31 patients (46.3%) had hyperthyroidism and 64.4% presented with subclinical thyroid dysfunction. In follow-up of thyroid dysfunction patients, 37 patients (74.0%) spontaneously regained normal thyroid function. Pretreatment thyroid-stimulating hormone (TSH) level, thyroid peroxidase antibody (TPOAb) positivity and free thyroxine (FT4) were independent risk factors associated with thyroid dysfunction incidence. High TSH level (OR = 9.866, 95%CI, 3.245-29.998) was associated with a greater likelihood of hypothyroidism. High FT4 levels (OR = 0.464, 95%CI, 0.248-0.868) indicate a low likelihood of thyroid dysfunction. Thyroid dysfunction is a common but acceptable side effect of IFN therapy for CHB. Most thyroid dysfunction is reversible. Pretreatment TSH level and TPOAb positivity are risk factors for thyroid dysfunction development during IFN therapy. A high TSH level predicts an increased incidence of hypothyroidism. Moreover, FT4 may be a protective factor for thyroid dysfunction.

Enhanced tumor accumulation and therapeutic efficacy of liposomal drugs through over-threshold dosing.

BACKGROUND: Most intravenously administered drug-loaded nanoparticles are taken up by liver Kupffer cells, and only a small portion can accumulate at the tumor, resulting in an unsatisfactory therapeutic efficacy and side effects for chemotherapeutic agents. Tumor-targeted drug delivery proves to be the best way to solve this problem; however, the complex synthesis, or surface modification process, together with the astonishing high cost make its clinical translation nearly impossible. METHODS: Referring to Ouyang's work and over-threshold dosing theory in general, blank PEGylated liposomes (PEG-Lipo) were prepared and used as tumor delivery enhancers to determine whether they could significantly enhance the tumor accumulation and in vivo antitumor efficacy of co-injected liposomal ACGs (PEG-ACGs-Lipo), a naturally resourced chemotherapeutic. Here, the phospholipid dose was used as an indicator of the number of liposomes particles with similar particle sizes, and the liposomes was labelled with DiR, a near-red fluorescent probe, to trace their in vivo biodistribution. Two mouse models, 4T1-bearing and U87-bearing, were employed for in vivo examination. RESULTS: PEG-Lipo and PEG-ACGs-Lipo had similar diameters. At a low-threshold dose (12 mg/kg equivalent phospholipids), PEG-Lipo was mainly distributed in the liver rather than in the tumor, with the relative tumor targeting index (RTTI) being ~ 0.38 at 72 h after administration. When over-threshold was administered (50 mg/kg or 80 mg/kg of equivalent phospholipids), a much higher and quicker drug accumulation in tumors and a much lower drug accumulation in the liver were observed, with the RTTI increasing to ~ 0.9. The in vivo antitumor study in 4T1 tumor-bearing mice showed that, compared to PEG-ACGs-Lipo alone (2.25 mg/kg phospholipids), the co-injection of a large dose of blank PEG-Lipo (50 mg/kg of phospholipids) significantly reduced the tumor volume of the mice by 22.6% (P < 0.05) and enhanced the RTTI from 0.41 to 1.34. The intravenous injection of a low drug loading content (LDLC) of liposomal ACGs (the same dose of ACGs at 50 mg/kg of equivalent phospholipids) achieved a similar tumor inhibition rate (TIR) to that of co-injection. In the U87 MG tumor-bearing mouse model, co-injection of the enhancer also significantly promoted the TIR (83.32% vs. 66.80%, P < 0.05) and survival time of PEG-ACGs-Lipo. CONCLUSION: An over-threshold dosing strategy proved to be a simple and feasible way to enhance the tumor delivery and antitumor efficacy of nanomedicines and was benefited to benefit their clinical result, especially for liposomal drugs.

Targeted antitumor comparison study between dopamine self-polymerization and traditional synthesis for nanoparticle surface modification in drug delivery.

To improve the therapeutic efficacy of anticancer agents and extend their application, mussel-inspired chemical modifications have attracted considerable attention. Surface modification based on polydopamine (PDA) has been a facile and versatile method to immobilize biomolecules on substrates for targeted drug delivery. To better analyze pharmaceutical differences between PDA-based surface modification and traditional synthesis methods, we prepared two kinds of folate (FA)-targeted nanoparticles (NPs) loaded with paclitaxel (PTX). The resultant PTX-PDA-FA NPs and PTX-FA NPs represented PDA and synthesis strategies, respectively. PTX-PDA-FA NPs and PTX-FA NPs have been characterized. The particle size of PTX-PDA-FA NPs was smaller than that of PTX-FA NPs. The two kinds of NPs both exhibited long-rod morphology, good colloidal stability and sustained slow drug release. Cytotoxicityin vitrowas evaluated, and antitumor efficacy was investigated against 4T1 tumor-bearing mice. The tumor targeting therapeutic index of PTX-PDA-FA NPs and PTX-FA NPs showed equivalent superior specificity compared to nontargeted groups, which indicated that FA successfully attached to the surface of NPs by the PDA method and that the antitumor effect was equivalent to that of FA-modified NPs prepared by the chemical synthesis method. These results further indicated that PDA, as a simple and effective chemical surface modification platform, could be developed and applied in targeted delivery systems.

Influence of Hydrophobic Chains in Nanocarriers on Antitumor Efficacy of Docetaxel Nanoparticles.

The composition of amphiphilic nanocarriers can affect the antitumor efficacy of drug-loaded nanoparticles and should be researched systematically. In this paper, to study the influence of hydrophobic chains, an amphiphilic copolymer (PEG45PCL17) and hydrophilic PEG (PEG45) were utilized as nanocarriers to prepare docetaxel-loaded nanoparticles (DTX/PEG45PCL17 nanoparticles and DTX/PEG45 nanoparticles) through an antisolvent precipitation method. The two DTX nanoparticles presented a similar drug loading content of approximately 60% and a sheet-like morphology. During the preparation procedure, the drug loading content affected the morphology of DTX nanoparticles, and the nanocarrier composition influenced the particle size. Compared with DTX/PEG45 nanoparticles, DTX/PEG45PCL17 nanoparticles showed a smaller mean diameter and better in vitro and in vivo antitumor activity. The cytotoxicity of DTX/PEG45PCL17 nanoparticles against 4T1 cells was 1.31 µg mL-1, 3.4-fold lower than that of DTX/PEG45 nanoparticles. More importantly, DTX/PEG45PCL17 nanoparticles showed significantly higher antitumor activity in vivo, with an inhibition rate over 80%, 1.5-fold higher than that of DTX/PEG45 nanoparticles. Based on these results, antitumor activity appears to be significantly affected by the particle size, which was determined by the composition of the nanocarrier. In summary, to improve antitumor efficacy, the amphiphilic structure should be considered and optimized in the design of nanocarriers.

Polydopamine-based surface modification of paclitaxel nanoparticles for osteosarcoma targeted therapy.

In order to achieve the purpose of targeting treatment of osteosarcoma, we developed novel paclitaxel (PTX) nanoparticles (Nps) coated with polydopamine (PDA) and grafted by alendronate (ALN) as ligand. Dopamine can be easily polymerized on various surfaces to form a thin PDA film in alkaline environment, which provided a versatile platform to perform secondary reactions for compounds without functional groups. The targeting Nps had a mean particle size of 290.6 ± 2.2 nm and a zeta potential of -13.4 ± 2.7. It was stable in phosphate buffer saline (PBS, pH 7.4), 5% glucose, plasma and displayed sustained drug release behavior. In vitro assay demonstrated the targeting Nps had stronger cytotoxicity against K7M2 wt osteosarcoma cells than the non-targeting Nps. Furthermore, in vivo distribution study indicated they could accumulate much more in tumor than non-targeting Nps. This is consistent with the in vivo antitumor study, targeting Nps achieved a better therapeutic effect than Taxol (8 mg kg-1, i.v.) (71.85% versus 66.53%) and prominently decreased the side effects of PTX. In general, the PTX-PDA-ALN-Nps may offer a feasible and effective strategy for osteosarcoma targeted therapy.

Amphiphilic Hybrid Dendritic-Linear Molecules as Nanocarriers for Shape-Dependent Antitumor Drug Delivery.

Nanoparticles based on hybrid block copolymers had been expected as effective nanocarriers for hydrophobic drug delivery. Herein, the novel dendritic-linear molecules from OEG dendron conjugated with octadecylamine (G2-C18) was designed, synthesized, and further applied as nanocarrier to prepare 10-hydroxycamptothecin (HCPT) nanoparticles via antisolvent precipitation method. It seemed that the feed weight ratio of HCPT vs G2-C18 not only affected the drug-loading content of nanoparticles but also influenced the morphology of HCPT nanoparticles; the morphology of HCPT nanoparticles was changed from nanosphere (NSs) to nanorod (NRs) with increasing the feed weight ratio. Both of HCPT nanoparticles presented good stability and similar drug release profiles, but different anticancer efficacy and cellular uptake mechanism. The cytotoxicity of HCPT NRs was enhanced significant comparing with HCPT NSs, the IC50 value was 2-fold lower than HCPT NSs ( p < 0.05). More importantly, HCPT NRs showed apparently higher antitumor activity in vivo, the inhibition rate of HCPT NRs was 1.3-fold higher than HCPT NSs. Based on these results, it suggested that the antitumor activity could be influenced significantly by particle morphology, which should be considered and optimized during the nanocarrier design.

Hydroxycamptothecin Nanorods Prepared by Fluorescently Labeled Oligoethylene Glycols (OEG) Codendrimer: Antitumor Efficacy in Vitro and in Vivo.

Nanorods based on dendrimers were explored as excellent candidates for nanoscale drug delivery system. In this study, fluorescently labeled PAMAM-b-oligoethylene glycols codendrimer (POC) was utilized as carrier to prepare 10-hydroxycamptothecin (HCPT) loaded nanorods (HCPT NRs) via antisolvent precipitation method augmented by ultrasonication with the optimized drug-loading content (∼90.6%) and positive charged surface. The nanorods presented high stability, and the release of HCPT nanorods showed a sustained release manner and was completed within 48 h. The nanorods presented higher cytotoxicity against HepG2 and 4T1 cells than HCPT injections, and the cellular uptake mechanism was proved to involve clathrin-mediated endocytosis and macropincytosis-dependent endobytosis. Importantly, the HCPT nanorods resulted in strong antitumor efficacy on the H22 liver tumor model, and no significant adverse effects was observed. Besides, in vivo studies also showed that HCPT NRs possessed better tumor accumulation over HCPT injection at the equivalent concentration. According to the high drug-loading content, enhanced antitumor efficacy, and appropriate particle size, HCPT NRs as the safe and efficient drug delivery systems could have potential application for cancer chemotherapy in clinic.

Biomass pyrolysis liquid to citric acid via 2-step bioconversion.

BACKGROUND: The use of fossil carbon sources for fuels and petrochemicals has serious impacts on our environment and is unable to meet the demand in the future. A promising and sustainable alternative is to substitute fossil carbon sources with microbial cell factories converting lignocellulosic biomass into desirable value added products. However, such bioprocesses require tolerance to inhibitory compounds generated during pretreatment of biomass. In this study, the process of sequential two-step bio-conversion of biomass pyrolysis liquid containing levoglucosan (LG) to citric acid without chemical detoxification has been explored, which can greatly improve the utilization efficiency of lignocellulosic biomass. RESULTS: The sequential two-step bio-conversion of corn stover pyrolysis liquid to citric acid has been established. The first step conversion by Phanerochaete chrysosporium (P. chrysosporium) is desirable to decrease the content of other compounds except levoglucosan as a pretreatment for the second conversion. The remaining levoglucosan in solution was further converted into citric acid by Aspergillus niger (A. niger) CBX-209. Thus the conversion of cellulose to citric acid is completed by both pyrolysis and bio-conversion technology. Under experimental conditions, levoglucosan yield is 12% based on the feedstock and the citric acid yield can reach 82.1% based on the levoglucosan content in the pyrolysis liquid (namely 82.1 g of citric acid per 100 g of levoglucosan). CONCLUSION: The study shows that P. chrysosporium and A. niger have the potential to be used as production platforms for value-added products from pyrolyzed lignocellulosic biomass. Selected P. chrysosporium is able to decrease the content of other compounds except levoglucosan and levoglucosan can be further converted into citric acid in the residual liquids by A. niger. Thus the conversion of cellulose to citric acid is completed by both pyrolysis and bio-conversion technology.

[Preliminary study on synthesis of novel amphiphilic molecules and their application as drug vectors].

OBJECTIVE: To synthesize three amphiphilic molecules (TEG-R1, TEG-R2, TEG-R3), with branched oligo polyethylene glycol as hydrophilic fractions and aliphatic chains (containing six, eight and twelve carbon atoms respectively) as hydrophobic fractions, and study them as insoluble drug vectors. METHOD: Three compounds were successfully through acylation, substitution reaction, reduction reaction and esterification. Their structures were verified by NMR analysis; and the critical micelle concentrations (CMC) of TEG-R1, TEG-R2, TEG-R3 were determined by pyrene fluorescence probe spectrometry. Transmission electronic microscopy (TEM) photos displayed the state of the aqueous solution. The self-assembly solution evaporation method was adopted to prepare drug loading podophyllotoxin micelles, and characterize their grain size, in order to detect the hemolysis of the three amphiphilic molecules. RESULT: Nuclear magnetism showed the successful synthesis of three amphiphilic molecules, with critical micelle concentrations of TEG-R1, TEG-R2, TEG-R3 of 50, 50, 10 mg x L(1), respectively. Transmission electronic microscopy (TEM) photos displayed a spherical-like state, with diameter of 20-50 nm. All of the three amphiphilic molecules could be prepared into drug-loading micelles, with the range of grain sizes between 100-200 nm. Hemdytic experiment showed that, among the amphiphilic molecules of the graft six-carbon aliphatic chain, TEG-R1 could not cause hemolysis. CONCLUSION: All of the three amphiphilic molecules are micellized in water solution, and can be used as insoluble drug vectors. Among them, TEG-R1 could not cause hemolysis, and is expected to become a new-type drug vector.

End-of-treatment anti-HBs levels and HBeAg status identify durability of HBsAg loss after PEG-IFN discontinuation.

Background: Hepatitis B surface antigen (HBsAg) loss, namely, the functional cure, can be achieved through the pegylated interferon (PEG-IFN)-based therapy. However, it is an unignorable fact that a small proportion of patients who achieved functional cure develop HBsAg reversion (HRV) and the related factors are not well described. Methods: A total of 112 patients who achieved PEG-IFN-induced HBsAg loss were recruited. HBV biomarkers and biochemical parameters were examined dynamically. HBV RNA levels were assessed in the cross-sectional analysis. The primary endpoint was HRV, defined as the reappearance of HBsAg after PEG-IFN discontinuation. Results: HRV occurred in 17 patients during the follow-up period. Univariable analysis indicated that hepatitis B e antigen (HBeAg) status, different levels of hepatitis B surface antibody (anti-HBs), and hepatitis B core antibody (anti-HBc) at the end of PEG-IFN treatment (EOT) were significantly associated with the incidence of HRV through using the log-rank test. Additionally, time-dependent receiver operating characteristic (ROC) analysis showed that the anti-HBs was superior to anti-HBc in predictive power for the incidence of HRV during the follow-up period. Multivariable Cox proportional hazard analysis found that anti-HBs ≥1.3 log10IU/L (hazard ratio (HR), 0.148; 95% confidence interval (CI), 0.044-0.502) and HBeAg negativity (HR, 0.183; 95% CI, 0.052-0.639) at EOT were independently associated with lower incidence of HRV. Cross-sectional analysis indicated that the HBV RNA levels were significantly correlated with the HBsAg levels in patients with HRV (r=0.86, p=0.003). Conclusions: EOT HBeAg negativity and anti-HBs ≥1.3 log10IU/L identify the low risk of HRV after PEG-IFN discontinuation.

Detection, detoxification, and removal of multiply heavy metal ions using a recyclable probe enabled by click and declick chemistry.

The pollution of water with heavy metal ions has generated great concern among both the public and academics due to the high toxicity, persistence, and non-degradability of heavy metals. The detection, detoxification, and removal of heavy metal ions are critical for monitoring water quality and treating polluted water. However, these tasks remain challenging due to lack of effective detection, detoxification, and removal strategies. By combining thiol-triggered click chemistry and heavy metal ion-triggered declick chemistry, a recyclable fluorescent probe for detecting numerous heavy metal ions was successfully developed through simple addition of thiol-containing heavy metal antidote to a carefully selected Michael acceptor-type fluorophore. The probe could be regenerated by adding equal amount of antidote to the detection solution without any purification step recycled up to 10 times. The generated water-soluble heavy metal ion-antidote complexes showed weak toxicity to biological systems, indicating successful detoxification. Finally, a simple, economical, and practical device for detecting, detoxifying, and removing heavy metal ions was fabricated by loading the recyclable fluorescent probe into polymer beads. The percent of detection, and removal are 98.10% and 97.59%, respectively. And detoxification percent is as high as 65.55%. The device is a promising candidate for water quality monitoring and treatment.

Reduction of Hepatitis B Surface Antigen May Be More Significant in PEGylated Interferon-Alpha Therapy Combined with Nucleotide Analogues than Combined with Nucleoside Analogues in Chronic Hepatitis B Patients: A Propensity Score Matching Study.

Background: Nucleotide analogues (NTs) monotherapy may have a more significant effect on reducing hepatitis B surface antigen (HBsAg) than nucleoside analogues (NSs) due to their immunomodulatory function. However, this superiority remains unknown when combined with PEGylated interferon α (PegIFNα). Therefore, this study aimed to explore whether NTs have more significant antiviral effects than NSs in combination therapy with PegIFNα. Methods: Chronic hepatitis B (CHB) patients treated with PegIFNα plus nucleos(t)ide analogues (NAs) were retrospectively recruited. Efficacy and the predictors of hepatitis B surface antigen (HBsAg) reduction >1 log10 IU/mL after 48 weeks were analyzed. Results: A total of 95 patients were included and divided into the PegIFNα + NTs group and the PegIFNα + NSs group. Propensity score matching (PSM) was performed. The PegIFNα + NTs group had a greater reduction of HBsAg (-3.52 vs. -2.33 log10 IU/mL, P=0.032) and a higher proportion of patients with HBsAg reduction >1 log10 IU/mL (100.0% vs. 72.2%, P=0.003) even after PSM. However, HBsAg and hepatitis B e-antigen (HBeAg) loss rates, HBeAg seroconversion rates, degree of HBeAg and hepatitis B virus (HBV) DNA decline, HBV DNA undetectable rates, and alanine aminotransferase (ALT) normalization rates showed no significant differences. Subgroup analyses showed the difference in the reduction of HBsAg was particularly evident in HBeAg-positive and the "add-on" subgroups. PegIFNα plus NTs (OR = 36.667, 95% CI = 3.837-350.384) was an independent predictor for HBsAg reduction >1 log10 IU/mL after 48 weeks. Conclusion: This study suggests that PegIFNα plus NTs may lead to more HBsAg reduction, especially in HBeAg-positive and "add-on" patients.

Potential health risk of areca nut consumption: Hazardous effect of toxic alkaloids and aflatoxins on human digestive system.

Contemporarily, there has been a growing consumption rate of areca nut (AN) products worldwide, despite the fact that both fresh and processed AN contain various hazardous ingredients, including toxic alkaloids and carcinogenetic aflatoxins. However, there is a dearth of toxicity and potential cancer risk information regarding toxic alkaloids and aflatoxins via consuming AN products. The present study conducted a comprehensive assessment of the combined hazardous effects of AN alkaloids and aflatoxins towards human digestive system, by methods of HPLC analysis, cell study and in vitro digestive system study. The results revealed a synergetic effect of arecoline and aflatoxins was on human gingival normal fibroblast cell of HGF-1 and a proliferation effect on human tongue squamous carcinoma cell of CAL-27. Specifically, the residual arecoline was as high as 91.08 µg·ml-1 in oral phase and 72.41 µg·ml-1 in gastric phase, which could be an evidence of oral cancer. More importantly, 25.93 % of AN products were contaminated with aflatoxins and the maximum value was three times the MRLs. Under these circumstances, the cytotoxic and MOE values raised a considerable health concern in terms of malignancy risk for children that consume processed AN product, especially compared to scenarios that involve adults and/or fresh AN samples. This study would give rise to a better understanding of the hazards associated with AN alkaloids and aflatoxins towards digestive system, and thus to predict the potential carcinogenic risk of AN products.

Honokiol-Based Nanomedicine Decorated with Ethylene Glycols Derivatives Promotes Antitumor Efficacy.

Honokiol-loaded nanoparticles (HK-loaded NPs) exhibit potential antitumor activity; however, the factors affecting their antitumor efficacy are still unclear and need to be explored. This research was aimed to systematically estimate the influence of feed weight ratio (FWR) and nanocarrier structure on antitumor activity. Accordingly, three types of ethylene glycol derivatives, including linear poly(ethylene glycol) with molar mass of 2000 (PEG45), first and second generation oligo(ethylene glycol) dendrons (G1 and G2) were used as nanocarriers, and a series of HK-loaded NPs with different FWR were prepared successfully using the evaporation-ultrasonication method. These NPs showed similar stability but demonstrated differences with respect to particle size, morphology, cumulative profile, and antitumor efficacy. The influence of the FWR was studied using G1 dendrons as nanocarriers; the results indicated that the particle size and morphology of G1 NPs were significantly affected, and G1 NPs (8/1), with the FWR of 8/1 for HK versus G1 dendron, exhibited the highest antitumor activity among all G1 NPs. Furthermore, the influence of nanocarrier structure was investigated at the FWR of 4/1; the findings revealed reduction in the particle diameter from 280 nm to 109 nm and change in morphology from sphere to flower-like structure with an increase in the branch degree from linear to dendron. Moreover, G2 NPs (4/1), with the FWR of 4/1 for HK versus G2 dendron, carrying the highest branch degree exhibited the greatest antitumor efficacy among all. These results are suggestive of influence of particle size and morphology on antitumor efficacy of HK-loaded NPs. Conclusively, this study demonstrated nanocarrier structure and the FWR significantly affect the antitumor efficacy of NPs, which should be optimized for designing nanoscale delivery systems.

Poly(methacrylate citric acid) with good biosafety as nanoadsorbents of heavy metal ions.

Heavy metal ion in aqueous solutions has been a challenge to human health. Discovering efficient adsorbents to remove heavy metal ion from water can help address this problem. In this study, poly(methacrylate citric acid) (PCA) with a well-defined structure based on a hydrophilic citric acid monomer was synthesized and then applied as a nanoadsorbent to remove several heavy metal ion. PCA presented excellent solubility in aqueous solution, and after freeze-drying, a loose porous structure was observed. PCA exhibited higher adsorption capacity for all the heavy metal ions (Cu2+, Pb2+, and Cd2+) than citric acid, and had a selectivity for Pb2+ ions with a removal efficiency of >90%. PCA also showed a good selectivity for adsorption of Pb2+ in a Chinese medicine decoction, with a removal rate >50%, while the concentration of active ingredient was maintained. Cell cytotoxicity in a cell model and system toxicity in mice indicated good biosafety of PCA. These results suggested that PCA with a good biosafety could be utilized as nanoadsorbent to remove Pb2+ ion from aqueous solution and decoction.

A comparative study on the in vitro and in vivo antitumor efficacy of icaritin and hydrous icaritin nanorods.

Icaritin (ICT) and hydrous icaritin (HICT) are two similar flavonoids compounds isolated from Epimedium Genus. This is the first comparative study on their in vitro and in vivo antitumor effects. Nanorods (NRs) were prepared for ICT and HICT by anti-solvent precipitation method using D-alpha tocopherol acid polyethylene glycol succinate (TPGS) as a stabilizer. The prepared ICT-NRs and HICT-NRs had similar diameter (155.5 nm and 201.7 nm), high drug loading content (43.30 ± 0.22% and 41.08 ± 0.19%), excellent stability and a similar sustaining drug release manner. Nanorods improved the in vitro toxicity against 4 different cancer cells in contrast to free ICT or free HICT; however, no significant difference was observed in this regard between ICT-NRs and HICT NRs. In the in vivo study on the anticancer efficacy on MCF-7 and PLC/PRE/5 tumor-bearing mice model, HICR-NRs displayed certain advantage over ICT NRs with higher tumor inhibition rate.

Surface modification of pH-sensitive honokiol nanoparticles based on dopamine coating for targeted therapy of breast cancer.

At present, there is a higher demand for the efficacy of nanoparticle drugs. It is hoped that more drugs will reach the tumor site and that the drug will be less harmful to other normal cells of the body before reaching the tumor site. Most target research for nanomedicine can achieve better positioning through complex processes, such as synthesis. To overcome these difficulties, such as the complexity of the preparation method and lack of good targeting, we used simple polydopamine (PDA) as a pH-sensitive targeting anchor for nanoparticles (NPs). We successfully conjugated folic acid (FA) to the surface of honokiol (HK) nanoparticles coated with PDA using a typical surface modifier. After preparation into HK-PDA-FA-NPs, we characterized the particle size, potential and transmission electron microscope (TEM). The targeted nanoparticles (HK-PDA-FA-NPs) can be stably present in various physiological media and exhibit pH sensitivity during drug release in vitro. HK-PDA-FA-NPs have better targeting ability to 4T1 cells than HK-NPs. Targeted nanoparticles have a tumor inhibition rate of greater than 80% in vivo, which is significantly higher than ordinary HK-NPs. This experiment shows that surface modification of HK-NPs coated with PDA is a promising preparation method for targeted therapy.

A comparative study of polydopamine modified and conventional chemical synthesis method in doxorubicin liposomes form the aspect of tumor targeted therapy.

Polydopamine (PDA) has been a simple, novel and versatile method to prepare targeted nanoparticles, which can be used as a platform for conjugating targeted ligands to polymer carriers without reactive chemical groups. To better understand the difference between the novel PDA method and conventional chemical synthesis way, we developed two kinds of folate (FA)-targeted liposomes loaded doxorubicin (DOX) by the above methods. FA-PDA-DOX liposomes and DOX-FA liposomes represented PDA and conventional method, respectively. FA-PDA-DOX liposomes had a smaller particle size than DOX-FA liposomes, and both of them presented good stability, spherical morphology, strong inhibition effect to HeLa cells and high drug accumulation in the tumor site. There were no significant differences between the two targeted liposomes in the in vitro cytotoxicity study and in vivo bio-distribution assay. While only FA-PDA-DOX liposomes showed pH-sensitive properties, which was attributed to the PDA layers and can control the drug release better. Compared to DOX-FA liposomes, FA-PDA-DOX liposomes were much safer in an antitumor experiment in vivo, and the inhibition rate was still over 70%. This study demonstrated the PDA method could achieve therapeutic levels similar to traditional methods in a simpler and safer way, which can be useful and promising nanocarriers for drug delivery system in the future.