Dawei Gao

An evaluation of the anti-tumor efficacy of oleanolic acid-loaded PEGylated liposomes

The effective delivery of oleanolic acid (OA) to the target site has several benefits in therapy for different pathologies. However, the delivery of OA is challenging due to its poor aqueous solubility. The study aims to evaluate the tumor inhibition effect of the PEGylated OA nanoliposome on the U14 cervical carcinoma cell line. In our previous study, OA was successfully encapsulated into PEGylated liposome with the modified ethanol injection method. Oral administration of PEGylated OA liposome was demonstrated to be more efficient in inhibiting xenograft tumors. The results of organ index indicated that PEG liposome exhibited higher anti-tumor activity and lower cytotoxicity. It was also found that OA and OA liposomes induced tumor cell apoptosis detected by flow cytometry. Furthermore, effects of OA on the morphology of tumor and other tissues were observed by hematoxylin and eosin staining. The histopathology sections did not show pathological changes in kidney or liver in tested mice. In contrast, there was a significant difference in tumor tissues between treatment groups and the negative control group. These observations imply that PEGylated liposomes seem to have advantages for cancer therapy in terms of effective delivery of OA.

Preparation and study on anti-tumor effect of chitosan-coated oleanolic acid liposomes

The purpose of this work was to prepare and study the anti-tumor effect of chitosan-coated oleanolic acid (OA) liposomes. The chitosan-coated OA liposomes had marked positive charges (19.9 ± 0.814 mV), which were inclined to combine with the negative charges on the surface of tumor cells, and then targeted and inhibited the growth of tumor cells. The average size of the chitosan-coated OA liposomes was around 167.44 nm, and this dimension was more easily trapped into the tumor tissue. The chitosan-coated OA liposomes possessed stronger rigidity and stability than those of ordinary liposomes, which can prevent the leakage of encapsulated drugs from liposomes. The Fourier transform infrared spectroscopy (FTIR) result indicated that chitosan already anchored the liposomes successfully. The chitosan-coated OA liposomes exhibited a slow, controlled OA release at pH 7.4, and a rapid release at pH 5.5 in vitro, which was beneficial for controlling tumor-targeting drug release. Additionally, MTT experimental results proved that the chitosan-coated OA liposomes can achieve more ideal anti-tumor effects than OA solution and OA liposomes. The study showed that chitosan modified liposomes not only solve the poor water solubility of OA, but also improve the anti-tumor efficacy, hence, it is a most promising drug carrier.

Preparation of adenovirus-templated gold nanoshells and a study of their photothermal therapy efficacy

A novel biotemplating method for fabricating gold nanoshells (AuNSs) through direct co-incubation of AuCl3 solution and an adenovirus shuttle vector-GFP (Adv) template in water, followed by the reduction of the mixture using fresh NaBH4, has been investigated in this paper. For comparison, different adenovirus-templated gold nanoshells (Adv-AuNSs) were prepared by modifying Adv with chitosan or changing the ionic conditions of the reaction system. The morphology and structure of the prepared AuNSs were characterized using transmission electron microscopy (TEM) and X-ray diffraction (XRD). The result indicated that Adv-AuNSs prepared by co-incubation of naked Adv and 7.5 mM AuCl3 solution had a uniform structure of approximately 120 nm diameter and face-centered cubic (fcc) crystal structure in the XRD pattern. A study of the biocompatibility of the prepared Adv-AuNSs demonstrated that there was no significant cytotoxicity. In addition, the photothermal therapy efficacy of the Adv-AuNSs on tumor cells was investigated in detail, revealing that all tumor cells could be killed when the power of near-infrared light irradiation was 4 W cm−2. Therefore, the prepared Adv-AuNSs will have very promising applications in the photothermal therapy of tumors.

Highly stable and biocompatible dendrimer-encapsulated gold nanoparticle catalysts for the reduction of 4-nitrophenol

The development of stable and biocompatible gold nanoparticles has been drawing great interest. Dendrimers could be used as templates to entrap gold nanoparticles. Herein, dendrimer templates were prepared by the modification of generation 5 polyamidoamine (G5 PAMAM) dendrimers with maleic anhydride and cysteamine. Then modified dendrimer-encapsulated gold nanoparticles (Au-G5MC NPs) were formed by incubation of the templates with chloroauric acid and reduction with sodium borohydride. The resulting Au-G5MC NPs showed high stability, biocompatibility, and catalytic efficiency in water, which is ascribed to the single zwitterionic layer composed of amine and carboxyl groups. The single zwitterionic layer was shown to provide the Au-G5MC NPs with excellent stability in both phosphate-buffered saline and fibrinogen solutions. The mixed solution of Au-G5MC NPs with fibrinogen remained stable within 24 h, while the mixed solution of G5 PAMAM dendrimer-entrapped gold nanoparticles (Au-G5 NPs) with fibrinogen formed obvious aggregates immediately. Au-G5MC NPs displayed little cytotoxicity (>90% cell viability) against HeLa cells up to 100 μg mL−1, while Au-G5 NPs showed obvious cytotoxicity (60% cell viability). In addition, Au-G5MC NPs displayed high catalytic efficiency for the reduction reaction of 4-nitrophenol (4-NP) in water. This method can be used to prepare a variety of highly stable, biocompatible, and efficient dendrimer-encapsulated catalysts.

An evaluation of anti-tumor effect and toxicity of PEGylated ursolic acid liposomes

Therapy of solid tumors mediated by nano-drug delivery has attracted considerable interest. In our previous study, ursolic acid (UA) was successfully encapsulated into PEGylated liposomes. The study aimed to evaluate the tumor inhibition effect and cytotoxicity of the PEGylated UA liposomes by U14 cervical carcinoma-bearing mice. The liposomes were spherical particles with mean particle diameters of 127.2xa0nm. The tumor inhibition rate of PEGylated UA liposomes was 53.60xa0% on U14 cervical carcinoma-bearing mice, which was greater than those of the UA solution (18.25xa0%) and traditional UA liposome groups (40.75xa0%). The tumor cells apoptosis rate of PEGylated UA liposomes was 25.81xa0%, which was significantly higher than that of the traditional UA liposomes (13.37xa0%). Moreover, the kidney and liver did not emerge the pathological changes in UA therapeutic mice by histopathological analysis, while there were significant differences on tumor tissues among three UA formulation groups. The PEGylated UA liposomes exhibited higher anti-tumor activity and lower cytotoxicity, and the main reason was that the coating PEG layer improved UA liposome properties, such as enhancing the stability of liposomes, promoting the effect of slow release, and prolonging the time of blood circulation. This may shed light on the development of PEGylated nano-vehicles.Graphical Abstract

Self-assembly of adenovirus-templated platinum nanoshells and evaluation of their biocompatibilities

In this study, the self-assembly of platinum nanoshells (PtNSs) in facile conditions, using the adenovirus shuttle vector-GFP (Adv) as a biotemplate, was achieved. This novel and simple biotemplating method can be summarized as direct co-incubation of the template Adv and PtCl4 solution, followed by the reduction of the co-incubation solution using NaBH4. The prepared Adv–PtNSs were then characterized by TEM, XRD and FTIR. The TEM results indicated that Adv–PtNSs, with good morphologies and monodispersity, can be obtained by controlling the concentration of PtCl4 as 7.5 mM, and the obtained Adv–PtNSs were about 100 nm. The results of XRD and FITR demonstrated that the prepared Adv–PtNSs were in a face-centered cubic structure, and the combination between the Adv and platinum complex ions mainly depended on –NH groups. In addition, the biocompatibilities of the prepared Adv–PtNSs to H9c2 cells were investigated. MTT assay results showed that as-prepared Adv–PtNSs had relatively high biocompatibilities, and caused almost no harm to H9c2 cells. Therefore, Adv–PtNSs have great potential as bioelectrode materials for monitoring the states of organisms.

Self-assembled platinum nanochains based on octreotide acetate

Biological scaffolds are used for the synthesis of inorganic materials due to their ability to self-assemble and nucleate crystal formation. We reported a facile method for preparing self-assembled Pt nanochains by using octreotide acetate (AOC) as bio-template in aqueous environment. The influence of solution pH was examined to define the optimal conditions for the formation of the AOC bio-templated Pt nanoparticles (PtNPs) arrays, the AOC has diameter about 55xa0nm at pH 2.0, for comparison, at pH 9.0, the diameter of AOC is about 25xa0nm. After 24-h incubation of AOC (pH 2.0) with PtCl4 and chemical reduction with borane-dimethyl-amine, uniform platinum nanoparticles (mean diameter 2.5xa0±xa00.5xa0nm) directed by AOC were formed. Preliminary characterizations of the synthesized PtNPs were performed using transmission electron microscopy, high-resolution transmission electron microscopy, energy dispersive spectroscopy, and selected area of electron diffraction. The cytotoxicity of Pt/octreotide acetate complexes (PtNPs–AOC) and AOC was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The results indicated that the antiproliferative effect of PtNPs–AOC is as high as AOC. In addition, the nano-design architecture of the Pt particles plays a crucial role in a strong enhancement of the biological efficiency of radiations, making PtNPs–AOC a promising material for anticancer drug delivery in the future.

Fabrication of gold nanochains with octreotide acetate template

We described a facile method for assembly gold nanochains by using octreotide acetate as template in aqueous environment. In acidic solution, octreotide acetatewas conferred positive charges and its structure changed to chain-like. The monodisperse negative gold nanoparticles were bound to the surface of octreotide acetate template by electrostatic attraction and the interaction of gold nanoparticles with amino acid residues (tryptophan and lysine). The fabricated gold nanostructure presented chain-like observed by transmission electron microscopy. The cytotoxicity of gold nanochains was examined by tetrazolium dye-based microtitration (MTT) assay, which demonstrated significantly less toxicity than that of octreotide acetate alone. The MTT assay also reflected the combinative action between the gold nanoparticles with octreotide acetate. Ourwork lays the groundwork for developing octreotide acetate-templated nanomaterials that can be used as a building block for the creation of nanomaterials. Meanwhile, the harmfulless gold nanochains have great application prospects in the biomedical filed.

Doxorubicin/gold nanoparticles coated with liposomes for chemo-photothermal synergetic antitumor therapy

Hybrid liposome/metal nanoparticles are promising candidate drug-carriers for therapy of various diseases due to their unique photothermal effect. In this study, self-crystallized gold nanoparticles (Au NPs) and doxorubicin (DOX) were co-encapsulated within liposomes (Au/DOX-Lips) by thin film hydration and gel separation technology. The surface plasmon resonance bands of drug-carriers were controllable in the near-infrared (NIR) zone. When the complex liposome/metallic hybrids were irradiated by NIR light, they displayed higher endocytosis efficiency following the fracture of liposomal membranes and the release of Au NPs. Then, the Au NPs penetrated further into deeper tumor tissue to accomplish photothermal treatment. The Au/DOX-Lips showed an excellent antitumor effect, whose inhibition rate for tumor cells was up to 78.28%. In experiments on mice bearing tumors, the Au/DOX-Lips treated mice exhibited superior tumor suppression. This novel drug system provides huge potential for biomedical application.

Octreotide acetate-templated self-assembly Pt nanoparticles and their anti-tumor efficacy

Platinum nanoparticles (PtNPs) were assembled in a chain-like structure by activating chemical groups of the octreotide acetate (AOC) template. Tumor-bearing mice were inoculated with cervical carcinoma cells, and then treated with a low dose of AOC-PtNPs (AOC-PtNPs-L), a high dose of AOC-PtNPs (AOC-PtNPs-H), sterile physiological saline and cyclophosphamide. The results suggested that tumor inhibition rates of cyclophosphamide, AOC-PtNPs-L and AOC-PtNPs-H were 87.0%, 38.3% and 42.5%; and the apoptosis rates of the tumor-bearing mice were 30.95%, 23.41% and 26.64%, respectively. More importantly, the histopathological study results implied that AOC-PtNPs had no toxicity or side-effects on liver and kidney tissues, but obvious inhibitory effects on tumors. In addition, MTT assay results showed that the as-prepared AOC-PtNPs had a higher inhibition rate on Hela cells than that of AOC or PtNPs alone. Therefore, AOC-PtNPs have great potential as anti-tumor drugs for cancer therapy in the future.