Shengnan Huang

Folic acid mediated solid lipid nanocarriers loaded with docetaxel and oxidized single-walled carbon nanotubes

Single-walled carbon nanotubes (SWNT) possess high-near-infrared absorption coefficient, large surface area, and have great potential in drug delivery. In this study, we obtained ultrashort oxidized SWNT (OSWNT) using mixed acid oxidation method. Then, docetaxel (DTX) and folic acid (FA) are conjugated with OSWNT via π–π accumulation and amide linkage, respectively. A targeting and photothermal sensitive drug delivery system FA–DTX–OSWNT–SLN was prepared following a microemulsion technique. The size and zeta potential of FA–DTX–OSWNT–SLN were 182.8xa0±xa02.8xa0nm and −34.59xa0±xa01.50xa0mV, respectively. TEM images indicated that FA–DTX–OSWNT–SLN was spherical and much darker than general solid lipid nanoparticles (SLN). Furthermore, OSWNT may wind round, insert into or be encapsulated into the nanocarriers. Compared with free DTX, FA–DTX–OSWNT–SLN could efficiently cross cell membranes and afford higher antitumor efficacy in MCF-7 cells in vitro. Meanwhile, the combination of near-infrared laser (NIR) irradiation at 808xa0nm significantly enhanced cell inhibition. In conclusion, FA–DTX–OSWNT–SLN drug delivery system in combination with 808xa0nm NIR laser irradiation may be promising for targeting and photothermal cancer therapy with multiple mechanisms in future.

Thermo-sensitive liposomes loaded with doxorubicin and lysine modified single-walled carbon nanotubes as tumor-targeting drug delivery system

This report focuses on the thermo-sensitive liposomes loaded with doxorubicin and lysine-modified single-walled carbon nanotube drug delivery system, which was designed to enhance the anti-tumor effect and reduce the side effects of doxorubicin. Doxorubicin-lysine/single-walled carbon nanotube-thermo-sensitive liposomes was prepared by reverse-phase evaporation method, the mean particle size was 232.0u2009±u20095.6u2009nm, and drug entrapment efficiency was 86.5u2009±u20093.7%. The drug release test showed that doxorubicin released more quickly at 42℃ than at 37℃. Compared with free doxorubicin, doxorubicin-lysine/single-walled carbon nanotube-thermo-sensitive liposomes could efficiently cross the cell membranes and afford higher anti-tumor efficacy on the human hepatic carcinoma cell line (SMMC-7721) cells in vitro. For in vivo experiments, the relative tumor volumes of the sarcomaia 180-bearing mice in thermo-sensitive liposomes group and doxorubicin group were significantly smaller than those of N.S. group. Meanwhile, the combination of near-infrared laser irradiation at 808u2009nm significantly enhanced the tumor growth inhibition both on SMMC-7721 cells and the sarcomaia 180-bearing mice. The quality of life such as body weight, mental state, food and water intake of sarcomaia 180 tumor-bearing mice treated with doxorubicin-lysine/single-walled carbon nanotube-thermo-sensitive liposomes were much higher than those treated with doxorubicin. In conclusion, doxorubicin-lysine/single-walled carbon nanotube-thermo-sensitive liposomes combined with near-infrared laser irradiation at 808u2009nm may potentially provide viable clinical strategies for targeting delivery of anti-cancer drugs.

A54 peptide-mediated functionalized gold nanocages for targeted delivery of DOX as a combinational photothermal-chemotherapy for liver cancer

The combination of photothermal therapy and chemotherapy (photothermal–chemotherapy) is a promising strategy for cancer therapy. Gold nanocages (AuNCs), with hollow and porous structures and unique optical properties, have become a rising star in the field of drug delivery. Here, we designed a novel targeted drug delivery system based on functionalized AuNCs and evaluated their therapeutic effects in vitro and in vivo. We then loaded doxorubicin into this promising system, designated as DHTPAuNCs consisting of hyaluronic acid-grafted and A54 peptide-targeted PEGylated AuNCs. Its formation was corroborated by ultraviolet–visible spectroscopy, transmission electron microscopy and dynamic light scattering. This delivery platform needed hyaluronidase to release encapsulated drugs, meanwhile the acidic pH and near-infrared irradiation could accelerate the release. In addition, the results of cellular uptake demonstrate that this system could bind specifically with BEL-7402 cells. In vitro, we evaluated therapeutic effects of the DHTPAuNCs in BEL-7402 cells by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide assay. Moreover, in BEL-7402 tumor-bearing nude mice, its therapy effect in vivo was also evaluated. As expected, DHTPAuNCs exhibited excellent therapeutic effect by photothermal–chemotherapy, both in vitro and in vivo. In short, DHTPAuNCs with low toxicity showed great potential as a drug delivery system for cancer therapy.

In vitro and in vivo anti-cancer effects of targeting and photothermal sensitive solid lipid nanoparticles

Abstract This report focuses on the in vitro and in vivo anti-cancer effects evaluation of targeting and photothermal sensitive solid lipid nanoparticles (SLN) for the co-loading of docetaxel (DTX), oxidized single-walled carbon nanotubes (OSWNT) and folic acid (FA). Compared with free DTX, FA-DTX-OSWNT-SLN could efficiently cross cell membranes and afford higher antitumor efficacy on the human hepatic carcinoma cell line (SMMC-7721) in vitro. Annexin V-FITC/PI double staining further confirmed that FA-DTX-OSWNT-SLN induced higher apoptotic rates on SMMC-7721 cells. Meanwhile, the combination of near-infrared (NIR) laser irradiation at 808u2009nm with FA-DTX-OSWNT-SLN significantly enhanced cell inhibition. For in vivo experiments, the relative tumor volume of the sarcomaia 180 (S180) tumor-bearing mice in FA-DTX-OSWNT-SLN group was significantly smaller than that of control groups. Furthermore, when combining with NIR laser irradiation, the suppression on tumor growth was much stronger. In a word, FA-DTX-OSWNT-SLN in combination with 808u2009nm NIR laser could exhibit both in vitro and in vivo anti-tumor effects and may be a promising approach for cancer therapy.

Triple therapy of hepatocellular carcinoma with microRNA-122 and doxorubicin co-loaded functionalized gold nanocages

A combination of different therapy strategies has great potential to efficaciously treat malignant tumors, by virtue of their synergetic effects. Herein, a co-delivery system based on gold nanocages (AuNCs) was designed to deliver both doxorubicin (DOX) and microRNA-122 mimic (miR-122) for an enhanced cancer therapy. DOX was loaded into the AuNCs and miR-122 was condensed onto the surface of the functionalized AuNCs by an electrostatic interaction. Polyethyleneglycol (PEG) and hyaluronic acid (HA) were also introduced to the co-delivery system for targeted drug delivery. We evaluated the cellular uptake, biodistribution and anti-tumor effect in vitro and in vivo. Our results demonstrated an effective delivery of DOX and miR-122 into tumor cells and the tumor tissue. Importantly, the triple therapy, namely the combination of chemotherapy, gene therapy and photothermal therapy, mediated by this multifunctional drug delivery system, exhibited better anti-tumor effect than any single therapy, both in vitro and in vivo. Additionally, this drug delivery system caused insignificant toxicity to the major organs and had no obvious effect on the body weight of the mice. It could be concluded that multifunctional AuNCs are promising as a co-delivery vector for an enhanced anti-tumor effect.

Reverse multidrug resistance in human HepG2/ADR by anti-miR-21 combined with hyperthermia mediated by functionalized gold nanocages

Multidrug resistance (MDR) remains a formidable challenge to effective clinical cancer therapy. Herein, a nonviral gene delivery system HA/anti-miR-21/PPAuNCs to overcome MDR was reported. This system could condense the microRNA-21 inhibitor (anti-miR-21) into hyaluronic acid-conjugated and polyethylenimine-modified PEGylated gold nanocages (AuNCs) and had good stability. In vitro studies demonstrated that HA/anti-miR-21/PPAuNCs could enhance intracellular DOX accumulation in DOX-resistant HCC cells (HepG2/ADR cells) and increase the sensitivity to DOX of HepG2/ADR cells through upregulating PTEN protein expression mediated by anti-miR-21 and downregulating P-gp protein expression mediated by the hyperthermia of HA/PPAuNCs upon mild near-infrared irradiation. Furthermore, the therapeutic effects had been enhanced due to the combination of chemotherapy, gene therapy, and photothermal therapy. Besides, HA/anti-miR-21/PPAuNCs have a good biocompatibility. These findings can provide new insights and strategies for the treatment of cancers with MDR.

Construction and application of a liver cancer-targeting drug delivery system based on core–shell gold nanocages

Background In order to achieve drug targeting and controlled release, we have successfully developed a novel drug release system DOX/AuNCs-PM-HA with gold nanocages (AuNCs) as photothermal cores, thermally responsive copolymer P(NIPAM-co-Am) (PM) as the near-infrared (NIR) stimuli gatekeeper and hyaluronic acid as a targeting ligand as well as a capping agent. Methods Cell uptake and cell viability were investigated. In vivo photoacoustic tomography imaging in H22 tumor bearing mice was analyzed for the tumor targeting effect of the nanocomplexes. Antitumor efficacy and the tissue distribution in vivo were investigated. Results In vitro results demonstrated that the DOX/AuNCs-PM-HA had significant anticancer activity against SMMC-7721 cells under NIR irradiation. Furthermore, in vivo photoacoustic tomography imaging of the nanocomplexes in H22 tumor bearing mice could indicate effective tumor targeting. Our studies on antitumor efficacy and the tissue distribution in vivo showed that many DOX/AuNCs-PM-HA nanocomplexes could efficiently accumulate at the tumor site so that they could inhibit the tumor growth effectively with limited side effects. The in vitro and in vivo results confirmed that the tumor-targeting and controlled-release drug system DOX/AuNCs-PM-HA with the combination of chemotherapy and photothermal therapy showed strong anti-tumor effect and would have great potential for future cancer therapy. Conclusion This tumor targeting DOX/AuNCs-PM-HA nanocomplex responded not only to the external stimuli of NIR, but also the internal stimuli of hyaluronidase, providing the potential for pinpointed and multi-stimuli responsive intracellular drug release.

Gene Therapy and Photothermal Therapy of Layer-by-Layer Assembled AuNCs /PEI/miRNA/ HA Nanocomplexes

BACKGROUNDnMicroRNA (miRNA) therapy, which was widely considered to treat a series of cancer, has been confronted with numerous obstacles to being delivered into target cells because of its easy biodegradation and instability.nnnMETHODSnIn this research, we successfully constructed 11-mercaptoundecanoic acid modified gold nanocages (AuNCs)/polyethyleneimine (PEI)/miRNA/hyaluronic acid (HA) complexes (abbreviated as AuNCs/PEI/miRNA/HA) using a layer-by-layer method for target-specific intracellular delivery of miRNA by HA receptor mediated endocytosis.nnnRESULTSnThe results of UV spectra, hydrodynamic diameter and zeta potential analyses confirmed the formation of AuNCs/PEI/ miRNA/HA complex with its average particle size of ca. 153 nm and surface charge of ca. -9.43 mV. Next, we evaluated the antitumor effect of the nanocomplex mediated by the combination of gene therapy and photothermal therapy (PTT) against hepatocellular carcinoma (HCC) in vitro.nnnCONCLUSIONnOur experimental results indicated that the AuNCs/PEI/miRNA/HA complex effectively delivered miRNA to the target cells and its antitumor effect was significantly enhanced by the combination of gene therapy and photothermal therapy. In addition, anti-miR-181b could promote Bel-7402 cell arrest in S phase and improve TIMP-3 mRNA expression. All these results suggested that AuNCs/PEI/miRNA/HA gene delivery system with combination of gene therapy and photothermal therapy might be exploited for HCC treatment.