Jiandu Lei

Self-assembled targeted nanoparticles based on transferrin-modified eight-arm-polyethylene glycol–dihydroartemisinin conjugate

Poor delivery of insoluble anticancer drugs has so far precluded their clinical application. In this study, an efficient tumor targeted-nanoparticle delivery system, transferrin-eight-arm-polyethylene glycol–dihydroartemisinin nanoparticles (TF-8arm-PEG-DHA NPs) for the vehiculation of dihydroartemisinin (DHA) was first prepared and evaluated for its targeting efficiency and cytotoxicity in vitro and in vivo to Lewis lung carcinoma (LLC) cells, which overexpress transferrin receptors (TFRs). The synthesized TF-8arm-PEG–DHA NPs had high solubility (~102 fold of free DHA), relatively high drug loading (~10 wt% DHA), long circulating half-life and moderate particle size (~147 nm). The in vitro cytotoxicity and in vivo tumor growth inhibition studies in LLC-tumor bearing mice confirmed the enhanced efficacy of TF-modified 8arm-PEG-DHA NPs compared to free DHA and non-modified 8arm-PEG-DHA NPs. All these results together supported that the formulation developed in this work exhibited great potential as an effective tumor targeting delivery system for insoluble anticancer drugs.

Layer-by-Layer Fabrication of High-Performance Polyamide/ZIF-8 Nanocomposite Membrane for Nanofiltration Applications

The conventional blending fabrication for thin-film nanocomposite (TFN) membranes is to disperse porous fillers in aqueous/organic phases prior to interfacial polymerization, and the aggregation of fillers may lead to the significant decrease in membrane performance. To overcome this limitation, we proposed a novel layer-by-layer (LBL) fabrication to prepare a polyamide (PA)/ZIF-8 nanocomposite membrane with a multilayer structure: a porous substrate, a ZIF-8 interlayer, and a PA coating layer. The PA/ZIF-8 (LBL) membrane for nanofiltration applications was prepared by growing an interlayer of ZIF-8 nanoparticles on an ultrafiltration membrane through in situ growth and then coating it with an ultrathin PA layer through interfacial polymerization. The obtained PA/ZIF-8 (LBL) membrane exhibited both better permeance and selectivity than did the conventional PA/ZIF-8 TFN membrane because of the ZIF-8 in situ growth producing a ZIF-8 interlayer with more ZIF-8 nanoparticles but fewer aggregates. Compared with the pure PA membrane (the flux of 11.2 kg/m(2)/h and rejection of 99.6%) for dye removal, the obtained PA/ZIF-8 (LBL) membranes achieved a significant improvement in membrane permeance and selectivity. (Flux was up to 27.1 kg/m(2)/h, and the rejection reaches 99.8%.) This LBL fabrication is a promising methodology for other polymer nanocomposite membranes simultaneously having high permeance and good selectivity.

The influence of dispersed phases on polyamide/ZIF-8 nanofiltration membranes for dye removal from water

To investigate the influence of different dispersed phases on polyamide (PA)/ZIF-8 membrane properties, three different fabrication methods for dispersing ZIF-8 nanoparticles were developed to prepare the PA/ZIF-8(A) membranes (in aqueous phases), PA/ZIF-8(O) membranes (in organic phases), and PA/ZIF-8(B) membrane (in both the aqueous and organic phases), respectively. These PA/ZIF-8 membranes were characterized in detail by XRD, DLS, XPS, FTIR, SEM, AFM, and contact angle measurements, the results showed that the structure properties of the PA/ZIF-8 membranes were significantly dependent on the dispersed phases and ZIF-8 concentrations. The nanofiltration performance of the PA/ZIF-8 membranes was investigated for application in removing dye (Congo red) from water. For the PA/ZIF-8(A) and PA/ZIF-8(O) membranes, the flux and rejection were both improved at 0.05–0.15% (w/v) ZIF-8 concentration in a single phase and the PA/ZIF-8(O) membranes exhibited slightly higher fluxes than the PA/ZIF-8(A) membranes due to the better dispersion of hydrophobic ZIF-8 in organic phases. The PA/ZIF-8(B) membrane prepared by 0.10% (w/v) ZIF-8 concentration in both the aqueous and organic phases showed the best membrane performance among all prepared PA/ZIF-8 membranes: the flux significantly increased to two times that of the pure PA membrane, and the rejection was nearly 100%. Compared with the PA/ZIF-8(A) and PA/ZIF-8(O) membranes, the improvement on membrane performance of the PA/ZIF-8(B) membrane was achieved by a combination of the high ZIF-8 loading, good ZIF-8 distribution, and fewer ZIF-8 aggregates in the PA/ZIF-8 selective layer.

Self-assembled targeted folate-conjugated eight-arm-polyethylene glycol–betulinic acid nanoparticles for co-delivery of anticancer drugs

In this study, a targeted nanoparticle platform for co-delivery of anticancer drugs based on folate-conjugated eight-arm-polyethylene glycol-betulinic acid (F-8arm-PEG-BA) was first presented. F-8arm-PEG-BA was synthesized by introducing target molecules (folate) and drug molecules (betulinic acid, BA) to hydrophilic molecules (8arm-PEG). Then another anticancer drug, hydroxycamptothecin (HCPT), was encapsulated into the self-assembled nanoparticles from the conjugate by a simple nanoprecipitation method. These F-8arm-PEG-BA/HCPT nanoparticles (NPs) had a small size (∼120 nm), acceptable critical aggregation concentration (∼64.8 μg mL-1), and high drug loading (∼18 wt% BA and ∼16 wt% HCPT). Compared to the free drugs, the nanoparticles significantly improved the cellular cytotoxicity and exhibited an obvious synergistic effect by the co-delivery of two different anticancer drugs, BA and HCPT. Pharmacokinetics study revealed the nanoparticles could prolong the circulation of BA and HCPT in the blood. In vivo studies indicated that the nanoparticles enhanced tumor targeting and antitumor activity with lower systemic toxicity. In conclusion, F-8arm-PEG-BA/HCPT NPs have great potential for targeted chemotherapy for cancer.

Cellulose-graft-poly(L-lactic acid) nanoparticles for efficient delivery of anti-cancer drugs

Cellulose based carriers have the potential for sustained release of drugs, which can protect drugs and deliver them to the target site. Herein, BA-loaded cellulose-graft-poly(l-lactic acid) nanoparticles (CE-g-PLLA/BA NPs) were fabricated by employing cellulose (CE) and poly(l-lactic acid) (PLLA) as materials and betulinic acid (BA) as a model drug. Both drug-free and BA-loaded nanoparticles were spherical in shape with a uniform size of 100-170 nm. The release of BA from CE-g-PLLA/BA NPs was relatively slow. In vitro cytotoxicity studies with A549 and LLC cell lines suggested that CE-g-PLLA/BA NPs were slightly superior to BA in antitumor activity and CE-g-PLLA NPs were non-toxic. The antitumor effect of the CE-g-PLLA/BA NPs in a mouse tumor xenograft model exhibited much better tumor inhibition efficacy and fewer side effects than that of BA, strongly supporting their use as efficient carriers for anti-cancer therapy.

A novel self-assembled targeted nanoparticle platform based on carboxymethylcellulose co-delivery of anticancer drugs

Single-drug therapy for cancer is greatly hampered by its non-specific delivery to the target tissue, limited efficacies, poor tolerability, and resistance profiles. In order to overcome these limitations, we developed a new targeted nanoparticle platform for co-delivery of two different anticancer drugs. A conjugate based on carboxymethylcellulose (CMC) was first synthesized by introducing hydrophilic molecules (PEG), target molecules (folate), and drug molecules (betulinic acid) into CMC. Then another anticancer drug hydroxycamptothecine (HCPT) was encapsulated into the nanoparticles from the conjugate using a simple nanoprecipitation method. The obtained nanoparticles possessed appropriate size (∼180 nm), high drug loading efficiency (∼23 wt% BA, 21.15 wt% HCPT), a slow drug release rate, higher blood circulation half-time of free BA (6.4-fold) and HCPT (6.0-fold), and high synergetic activity of BA and HCPT toward cancer cells. Furthermore, the targeted nanoparticles showed rapid cellular uptake by tumor cells. The antitumor effect of the nanoparticles in a mouse tumor xenograft model exhibited a much better tumor inhibition efficacy and fewer side effects than that of BA and HCPT, strongly supporting their application as efficient carriers for anticancer therapy.

NiO-PTA supported on ZIF-8 as a highly effective catalyst for hydrocracking of Jatropha oil

Nickel oxide (NiO) and phosphotungstic acid (PTA) supported on a ZIF-8 (NiO-PTA/ZIF-8) catalyst was first synthesized and it showed high activity and good selectivity for the hydrocracking of Jatropha oil. The catalyst was characterized by SEM, SEM-EDS, TEM, N2 adsorption, FT-IR, XRD and XPS. Compared with the NiO-PTA/Al2O3 catalyst, the selectivity of C15-C18 hydrocarbon increased over 36%, and catalytic efficiency increased 10 times over the NiO-PTA/ZIF-8 catalyst. The prepared NiO-PTA/ZIF-8 catalyst was stable for a reaction time of 104 h and the kinetic behavior was also analyzed. This catalyst was found to bypass the presulfurization process, showing promise as an alternative to sulfided catalysts for green diesel production.

Novel Multiarm Polyethylene glycol-Dihydroartemisinin Conjugates Enhancing Therapeutic Efficacy in Non-Small-Cell Lung Cancer

The clinical application of dihydroartemisinin (DHA) has been hampered due to its poor water-solubility. To overcome this hurdle, we devised a novel polymer-drug conjugate, multiarm polyethylene glycol-dihydroartemisinin (PEG-DHA), made by linking DHA with multiarm polyethylene glycol. Herein, we investigated PEG-DHA on chemical structure, hydrolysis, solubility, hemolysis, cell cytotoxicity in vitro, and efficacy in vivo. The PEG-DHA conjugates have showed moderate drug loadings (2.82 ~ 8.14 wt%), significantly good water-solubilities (82- ~ 163-fold of DHA), excellent in vitro anticancer activities (at concentrations ≥8 μg/ml, showed only 15–20% cell viability) with potency similar to that of native DHA, and long blood circulation half-time (5.75- ~ 16.75-fold of DHA). Subsequent tumor xenograft assays demonstrated a superior therapeutic effect of PEG-DHA on inhibition of tumor growth compared with native DHA. The novel PEG-DHA conjugates can not only improve the solubility and efficacy of DHA but also show the potential of scale-up production and clinical application.

Water soluble multiarm-polyethylene glycol–betulinic acid prodrugs: design, synthesis, and in vivo effectiveness

Betulinic acid (BA) is a new type of cancer-fighting drug, but it is limited by its low water solubility and relatively short half-life in clinical applications. To overcome the shortcomings, BA prodrugs were prepared by using multiarm-polyethylene glycol linkers. The prodrugs exhibited high drug loading capacity (3.26–11.81 wt%), high water solubility (290–750 fold of free BA), and excellent in vitro anticancer activity. Subsequent tumor xenograft assays demonstrated the superior therapeutic effect of BA prodrugs on inhibition of tumor growth compared with free BA. Multiple intravenous injection of BA prodrugs equivalent to 10 mg of BA per kg resulted in the decrease of an established implanted murine Lewis lung carcinoma (percent tumor growth inhibition after treatment on day 20, 72.1–90.7%) in mice. These results strongly supported that the BA prodrugs are promising for cancer therapy.

Self-assembled serum albumin–poly(L-lactic acid) nanoparticles: a novel nanoparticle platform for drug delivery in cancer

We developed a new self-assembled bovine serum albumin–poly(L-lactic acid) nanoparticle platform for anticancer drug delivery made from a bovine serum albumin–poly(L-lactic acid) polymer conjugate. Depending on the ratio of bovine serum albumin (BSA) to poly(L-lactic acid) (PLLA), these conjugates self-assemble into uniform spherical nanoparticles with different sizes. Then, BA-loaded BSA–PLLA nanoparticles (BSA–PLLA/BA NPs) were prepared by using BSA–PLLA conjugates as prototype materials, and betulinic acid (BA) as a model drug. In vitro cytotoxicity studies with human lung cancer cell lines (A549) and murine Lewis lung carcinoma (LLC) cell lines suggested that the BSA–PLLA/BA NPs were significantly superior to the model drug BA in antitumor activity and the BSA–PLLA NPs were non-toxic. Compared to free BA, the BSA–PLLA/BA NPs provided significantly higher blood circulation half-time of free BA (5.02-fold). The antitumor effect of the BSA–PLLA/BA NPs in a mouse tumor xenograft model showed much better tumor inhibition efficacy and fewer side effects than that of free BA. It may be attributed to the preferential tumor accumulation and increases the solubility of the drug in water, strongly supporting their use as high-performance carriers for anti-cancer therapy.