In this study, an antitumor drug delivery system, gold nanoshell coated wedelolactone liposomes (AuNS-Wed-Lip), were designed and synthesized. In the drug delivery system, wedelolactone liposome and gold-nanoshell were linked by l-cysteine, which had been shown an effective nanocarrier for antitumor drug delivery, on-demand drug release, and phototherapy under near-infrared (NIR) light irradiation. It was capable of absorbing 780-850 nm NIR light and converting light energy to heat rapidly. The hyperthermia promoted wedelolactone release rapidly from the systems. The release amount of AuNS-Wed-Lip under NIR irradiation reached up to 97.34% over 8 h, achieving the on-demand drug release. Moreover, a high inhibition rate up to 95.73% for 143B tumor cells by AuNS-Wed-Lip upon laser irradiation at 808 nm was observed. The excellent inhibition efficacy was also displayed in vivo antitumor study with S180 tumor-bearing mice. The results demonstrated that AuNS-Wed-Lip, as an antitumor drug delivery system, achieved chemo-photothermal synergetic effect, which has great potential in cancer therapy.

Development of combined chemo-photothermal nanoplatform is of great interest for enhancing antitumor efficacy. Herein, a multifunctional drug delivery system was synthesized based on gold-nanobranched coated betulinic acid liposomes (GNBS-BA-Lips) for chemo-photothermal synergistic therapy. In this system, GNBS-BA-Lips exhibited broad near-infrared (NIR) absorption, preferable photothermal response and good photostability under NIR irradiation. Importantly, the gold-nanobranched nanostructure possessed high photothermal conversion efficiency (η = 55.7%), and the temperature change (ΔT) reached 43.2 °C after laser irradiation for 5 min. Upon NIR irradiation, the nanocarriers apparently endowed higher cell uptake, resulting in an enhanced intracellular drug accumulation. Furthermore, the tumor growth inhibition ratio achieved from chemo-photothermal therapy of GNBS-BA-Lips was 86.9 ± 1.1%, which was higher than that of the chemotherapy or photothermal therapy alone, showing an outstanding synergistic anticancer effect. Our data suggested that the nanoplatform should be considered as a critical platform in the development of cancer multi-mode therapies.

Synergistic cancer therapy through the combination of chemotherapy with photothermal therapy has been gained more and more insights. Bimetallic nanostructures with near-infrared (NIR) plasmonic responses are considered prime candidates based on their superior photo thermal conversion properties. Herein, novel poly branched Au-Pd bimetallic-nanoflowers-coated betulinic acid liposomes (BA-Lips@Pd@Au NFs) were designed and developed. The as-prepared BA-Lips@Pd@Au NFs with optimal size (144.4 nm) possessed good photostability under NIR-irradiation, high photothermal conversion efficiency (64.6%), and good biocompatibility. Moreover, the hyperthermia of drug delivery induced by NIR-irradiation dramatically improved the cell uptake of nanocapsules and enhanced the chemotherapeutic efficacy of tumor. Upon illumination by NIR light, the BA-Lips@Pd@Au NFs exhibited prominent synergetic effects of chemo-photothermal therapy with a tumor inhibition ratio (91.7%), which was higher than that of chemotherapy or photothermal therapy alone. Therefore, this rational design of nanocapsule with stimuli-responsive capability showed a versatile strategy to provide smart nanocapsule paradigms for cancer therapy.

Resveratrol (3,5,4′-trihydroxy-trans-stilbene, Res), as a natural product and neuroprotective drug, plays important roles in the treatment of Parkinson’s disease (PD). However, Res is seriously hindered by the blood–brain barrier (BBB), which limits the access of Res to the central nervous system. In addition, the differential diagnosis of PD has been considered one of the most challenging in neurology. Herein, a magnetic targeting drug nanocarrier, Fe3O4-modified Res liposomes (Res-lips@Fe3O4), was designed and fabricated. The factional anisotropy (FA) values and T2 relaxation time of the Res-lips@Fe3O4 treated rats were obtained by magnetic resonance imaging. The Res-lips@Fe3O4 possessed high drug capability and stability, which exhibited strong magnetic response properties. Res-lips@Fe3O4 displayed sustained and slow drug release in vitro. In vivo experiments showed that the Res-lips@Fe3O4 could effectively cross the BBB and increase the drug content at the target site under the external magnetic field...

A novel synthesis approach is first developed to fabricate a multifunctional smart nanodrug delivery system: gold nanoshell-coated betulinic acid liposomes (AuNS-BA-Lips) mediated by a glutathione. The AuNS-BA-Lips exhibited good size distribution (149.4±2.4nm), preferable photothermal conversion ability and synergistic chemo-photothermal therapy. Additionally, the absorption wavelength of AuNS-BA-Lips showed a significantly red-shifted to near infrared (NIR) region, which can strongly absorbed NIR laser and efficiently convert it into localized heat, thus providing controlled drug release and antitumor thermotherapy. Moreover, the nanocarriers excited by NIR light significantly promoted cell uptake compared to those without irradiation, resulting in an enhanced intracellular drug accumulation. Upon NIR irradiation, the AuNS-BA-Lips showed highly efficient antitumor effects on tumor-bearing mice with an inhibition rate of 83.02%, thus demonstrating a remarkable synergistic therapeutic effect of chemotherapy and thermotherapy. Therefore, this work provides new insight into developing a multifunctional antitumor drug.

Stimuli-responsive drug delivery and release have a great significance in cancer therapy. Herein, a multifunctional responsive drug carrier was designed and developed by loading resveratrol (Res) in chitosan (CTS) modified liposomes, and coated by gold nanoshells (GNS@CTS@Res-lips). The resultant GNS@CTS@Res-lips possess broad near-infrared (NIR) absorbance, high capability, stability, and also high photothermal conversion ability for efficient photothermal therapy (PTT) applications. In addition, the GNS@CTS@Res-lips exhibit the on-demand pH/photothermal-sensitive drug release, and a high loading capacity of Res. Under NIR laser irradiation, the drug delivery system could significantly enhance the cellular uptake of drugs. More importantly, compared to the single chemotherapy or PTT, the carriers with NIR irradiation displayed a higher therapeutic effect for HeLa cells. Therefore, the GNS@CTS@Res-lips with a combination of chemotherapy and PTT will show great potential for application in cancer therapy.

The dendrimer based synthetic mimetic enzyme has been drawing great attention. However, this mimetic enzyme is different from the natural enzymes, which are pH sensitive, biocompatible and keep their catalytic activity in biological complex medium. A single zwitterionic layer composed by primary amine and carboxyl groups may be a useful method to obtain these properties. Herein, we report a novel facile method to prepare a mimetic enzyme. The complexes of generation 5 poly(amido amine) dendrimers (G5 PAMAM) with free hemin (G5Hs) were modified by the maleic anhydride and cysteamine. Results showed that the mimetic enzymes (G5HMCs) had pH sensitivity and good stability by varying the pH from 4 to 9, while significant precipitation was observed for free hemin at pH5 after two days. The G5HMC (3:1) showed optimal catalytic activity at its isoelectric point. Furthermore, G5HMCs displayed excellent biocompatibility. The G5HMCs incubated with fibrinogen were stable for 24h, while G5Hs immediately formed large aggregates. G5HMC (3:1 2mg/mL) displayed little cytotoxicity with HeLa cells or A549 cells for 24h, while G5H (3:1) had serious cytotoxicity, which was also demonstrated by cell morphology observation. At last, G5HMCs fully preserved their catalytic activity in bovine serum albumin (BSA) solution compared with phosphate buffer saline (PBS) solution, while hemin decreased to 73.5-81.5% catalytic activity in BSA solution, which was caused by the less interaction with BSA for G5HMCs than free hemin. The surface functionalization schemes described in this report would represent a versatile method to prepare water-soluble, pH sensitive, biocompatible, and efficient artificial enzymes for biomedical related applications.

Betulinic acid (BA), as a natural pentacyclic lupine-type triterpene, principally derives from bark of white birch, due to its potent pharmacological properties and low side-effect, which has been demonstrated a prominent efficiency on cancer therapy. However, the poor solubility and low bioavailability limit its pharmaceutical effect. Herein, we reported the rapid efficient synthesis of the polyethylene glycol modified (PEGylated) BA liposomes using ethanol injection technique for the first time. In the study, hydrophobic BA was encapsulated in the lipid bilayer of liposomes, meanwhile hydrophilic PEG layer covered the surface of liposomes. The mean diameter of PEGylated BA liposomes was 142nm, which can effectively accumulate in the tumor tissues. In vitro drug release study showed that the PEGylated BA liposomes had a better sustained drug release effect than BA liposomes. The PEGylated BA liposomes also exhibited a better tumor inhibitory effect compared with those of free BA or BA liposomes in vitro and in vivo experiments. Therefore, the PEGylated BA liposomes could serve as a better alternative for the cancer therapy in future.

Gold nanoshell coated oleanolic acid liposomes mediating by chitosan (GNOLs), are designed and successfully synthesized for the first time by D. Gao and co-workers on page number 4103. An excellent near infrared (NIR) photothermal effect, pH-responsive drug controlled release and tumor targeting properties are demonstrated. By combining NIR photothermal therapy and chemotherapy, the smart drug delivery system exhibits a superior antitumor property in vitro and in vivo.

There are tremendous challenges on antitumor and its therapeutic drugs, and preparation of highly efficient nano-vehicles represents one of the novel topics in antitumor pharmaceutical field. Herein, the novel chitosan-coated ursolic acid (UA) liposome (CS-UA-L) was efficiently prepared with highly tumor targeting, drug controlled release and low side-effect. The CS-UA-L was uniformly spherical particles with diameter of ~ 130 nm, and the size was more easily trapped into the tumor tissues. Chitosan modification can make liposomes carrying positive charges, which were inclined to combine with the negative charges on the surface of tumor cells, and then the CS-UA-L could release UA rapidly at pH 5.0 comparing with pH 7.4. Meanwhile, the CS-UA-L exhibited obvious anti-proliferative effect (76.46%) on HeLa cells and significantly antitumor activity (61.26%) in mice bearing U14 cervical cancer. The tumor tissues of CS-UA-L treated mice had enhanced cell apoptosis, extensive necrosis and low cell proliferation activity. These results demonstrated that the multifunctional CS-UA-L allowed a precision treatment for localized tumor, and reducing the total drug dose and side-effect, which hold a great promise in new safe and effective tumor therapy.

In the study, a new photoresponsive nano drug delivery system was developed by encapsulating indocyanine green into liposomes (ICG-liposomal wedelolactone), which could improve the water solubility and bioavailability of wedelolactone. The hyperthermia, produced by ICG under near-infrared (NIR) light irradiation, promoted wedelolactone release rapidly from the carriers. The release amount of ICG-liposomal wedelolactone under NIR irradiation reached up to 96.74% over 8h, achieving the drug of on-demand release. Moreover, the growth of HepG2 cells was obviously inhibited by ICG-liposomal wedelolactone under NIR, and the early apoptotic rate of HepG2 cells was 33.74%. The tumor inhibition rate was 81% in the mice bearing tumor treated with the drug system. The results proved that ICG-liposomal wedelolactone, as a novel drug delivery system to co-delivery chemotherapeutic agents and photothermal agents, achieved synergetic effect of chemotherapy and photothermotherapy, which will have an enormous potential in future cancer therapy.

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 127.2 nm. The tumor inhibition rate of PEGylated UA liposomes was 53.60 % on U14 cervical carcinoma-bearing mice, which was greater than those of the UA solution (18.25 %) and traditional UA liposome groups (40.75 %). The tumor cells apoptosis rate of PEGylated UA liposomes was 25.81 %, which was significantly higher than that of the traditional UA liposomes (13.37 %). 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.

Chitosan modified OA liposomes can achieve the desired effect of tumor-targeting drug delivery and improve the anti-tumor efficacy.

While ursolic acid (UA), one of the most broadly known triterpene compounds, has proved to be effective in cancer therapy, the applications of UA is limited due to its poor aqueous solubility and low bioavailability. The aim of our study was to prolong circulation time and enhance uptake of liposomes in tumor tissues through the modification of UA liposomes via water-soluble polyethylene glycol (PEG). In addition, this research also focuses on physicochemical properties of the liposome formulations, including encapsulation efficiency, particle morphology, size, stability, release rate in vitro and cytotoxicity test. The obtained liposomes were spherical particles with mean particle diameters around 100-200 nm. And the Fourier transform infrared spectroscopy (FTIR) indicated that PEG had been anchored successfully to the liposomes. Based on our experimental data achieved, PEG-modified UA liposomes possessed higher stability than conventional liposomes, and the release rate of UA from PEG-modified liposomes was slower when compared with those of UA solution and conventional liposomes. Meanwhile, the liposomal UA showed relatively low cytotoxic effect than UA conventional liposomes within 24h, which was consistent with their release rates.

Highly biocompatible and monodisperse platinum nanoshells with diameters of ∼100 nm were fabricated using adenovirus as sacrificial template.

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.

Gynostemma pentaphyllum (GP) is a natural plant resources for diabetes therapy, however, there is little research on the mechanisms of GP. The present study was undertaken to characterize if G. pentaphyllum saponins (GPs) is the principal active compound of GP responsible for anti-diabetes, and to examine the relativity between blood glucose modulate and antioxidation. The GPs-treated streptozotocin diabetic rats had a more effective hypoglycemic status than those of diabetic control rats, which also ameliorate dyslipidemia. GPs has increased SOD and GSH-px activities, and the spleen and thymus indexes in diabetic rats. The insulin levels in the GPs-treated groups were significantly higher than diabetic control group. Our finding provides a new insight into the application of GPs for the treatment of oxidative stress related diseases.

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.