Liyao Luo

Combined Near Infrared Photothermal Therapy and Chemotherapy Using Gold Nanoshells Coated Liposomes to Enhance Antitumor Effect.

Novel antitumor system based on the targeting photothermal and pH-responsive nanocarriers, gold nanoshells coated oleanolic acid liposomes mediating by chitosan (GNOLs), is designed and synthesized for the first time. The GNOLs present spherical and uniform size (172.03 nm) with zeta potential (20.7 ± 0.4 mV), which are more easily accumulated in tumor. Meanwhile, the GNOLs exhibit a slow and controlled release of oleanolic acid at pH 7.4, as well as a rapid release at pH 5.5, which is beneficial for tumor-targeting drug release. Under near infrared (NIR) irradiation, hyperthermia can be generated by activated gold nanoshells to perform photothermal therapy effect, which triggers drug release from the carriers by activating the gel to liquid crystalline phase transition of the liposomes. Moreover, the NIR assisting drug release can be easily and selectively activated locally due to the spatially and real-timely controllable property of light. The experimental results also verify that the GNOLs with NIR irradiation achieve more ideal antitumor effects than other oleanolic acid formulations in vitro and in vivo. Hence, the drug delivery system exhibits a great potential in chemo-photothermal antitumor therapy.

Antitumor drug effect of betulinic acid mediated by polyethylene glycol modified liposomes

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 thermo-pH dual responsive liposomes for resveratrol delivery and chemo-photothermal synergistic cancer therapy

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.

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.

Gold Nanoshell-Based Betulinic Acid Liposomes for Synergistic Chemo-Photothermal Therapy

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.

Gold Nanoshells: Combined Near Infrared Photothermal Therapy and Chemotherapy Using Gold Nanoshells Coated Liposomes to Enhance Antitumor Effect (Small 30/2016)

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.

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.

Fabrication of gold nanocages and nanoshells using lanreotide acetate and a comparison study of their photothermal antitumor therapy

Gold nanostructures, particularly gold nanocages or nanoshells (AuNCs or AuNSs), exhibit remarkable optical properties due to their excellent surface plasmon resonance, allowing their potential use in biomedical fields. Herein, we report the controlled synthesis of AuNCs and AuNSs simply using lanreotide acetate (Lan) as a biotemplate. Gold nanomaterials were obtained via co-incubation between a HAuCl4 solution and Lan peptide and controlling the reduction reaction process. AuNCs and AuNSs prepared in this method were about 120 nm and 150 nm in diameter, respectively, which have the desired passive targeting to tumor. Surprisingly, both AuNCs and AuNSs showed superior photothermal inhibitory effects for cancer cells with only 0.8 W cm−2 laser power in the in vivo and vitro experiments; moreover, the AuNCs showed better antitumor activity and photothermal conversion efficiency than the AuNSs. In this study, two kinds of gold nanostructures were fabricated using the same template molecule, and AuNCs showed higher photothermal conversion efficiency due to their anisotropic structure.

Trimodal synergistic antitumor drug delivery system based on graphene oxide

A multifunctional antitumor drug delivery system was synthesized based on graphene oxide (GO) for near-infrared (NIR) light controlling chemotherapeutic/photothermal (PTT) /photodynamic (PDT) trimodal synergistic therapy. The system named ICG-Wed-GO was formed by co-loading wedelolactone (Wed) and indocyanine green (ICG) on the surface of GO through π-π stacking interaction. Under NIR laser irradiation, ICG-Wed-GO could effectively absorb and transform optical energy to heat, generate reactive oxygen species (ROS) to ablating and damage tumor cells. The temperature of ICG-Wed-GO solution reached up to 79.4 °C in 10 min with NIR irradiation. In in vitro and in vivo study, ICG-Wed-GO showed excellent antitumor effect. After 14-day treatment of ICG-Wed-GO with NIR laser irradiation, the tumor disappeared completely on tumor-bearing mice. The low biotoxicity of ICG-Wed-GO was also proved. The system achieved the synergistic trimodal chemotherapeutic/photothermal/photodynamic treatment and demonstrated excellent antitumor effect, which is expected to have a greater potential for cancer therapy.

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.