Network-Based Pharmacological Study on the Mechanism of Guishao-Liujun Decoction in the Treatment of Gastric Cancer.

Objective: The aim of the study was to use a network pharmacological method to examine the mechanism of Guishao-Liujun decoction against gastric cancer (GC). Methods: The traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) and the Traditional Chinese Medicine Integrated Database (TCMID) were used to obtain the chemical composition and targets of all the drugs of Guishao-Liujun decoction, and the targets of GC were screened using GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. The obtained targets were imported into Cytoscape 3.7.2 software by using the R language to take the intersection for a Venn analysis to construct active ingredient target networks, and they were imported into the STRING database to construct protein-protein interaction (PPI) networks, with the BisoGenet plugin in Cytoscape 3.7.2 being used for analyzing network topology. On the potential target of Guishao-Liujun decoction for GC, gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed using the R-language bioconductor platform, and the outcomes were imported into Cytoscape 3.7.2 software to obtain the KEGG network map. The core targets were docked with the active components by the macromolecular docking software application AutoDock Vina. Results: A total of 243 chemical components and 1,448 disease targets including 127 intersecting targets were discovered. AKT1, TP53, and GO functional analysis were mainly associated with ubiquitination and oxidase reduction activity. In GC treatment, the KEGG analysis revealed that Guishao-Liujun decoction mainly acted through the tumor necrosis factor (TNF), interleukin 17 (IL-17), and cancer-related signaling pathways, with the best binding performance with TP53, as indicated by the outcomes of macromolecular docking. Conclusion: In the treatment of GC, Guishao-Liujun decoction works with a variety of components and targets, establishing the groundwork for further research into its mechanism of action.

Encountering and Wrestling: Neutrophils Recognize and Defensively Degrade Graphene Oxide.

The boosting exploitation of graphene oxide (GO) increases exposure risk to human beings. However, as primary defender in the first immune line, neutrophils' mechanism of defensive behavior toward GO remains unclear. Herein, we discovered that neutrophils recognize and defensively degrade GO in a lateral dimension dependent manner. The micrometer-sized GO (mGO) induces NETosis by releasing neutrophil extracellular traps (NETs), while nanometer-sized GO (nGO) elicits neutrophil degranulation. The two neutrophils' defensive behaviors are accompanied with generation of reactive oxygen species and activation of p-ERK and p-Akt kinases. However, mGO-induced NETosis is NADPH oxidase (NOX)-independent while nGO-triggered degranulation is NOX-dependent. Furthermore, myeloperoxidase (MPO) is determinant mediator despite distinct neutrophil phenotypes. Neutrophils release NETs comprising of MPO upon activated with mGO, while MPO is secreted via nGO-induced degranulation. Moreover, the binding energy between MPO and GO is calculated to be 69.8728 kJ mol-1 , indicating that electrostatic interactions mainly cause the spontaneous binding process. Meanwhile, the central enzymatic biodegradation occurs at oxygenic active sites and defects on GO. Mass spectrometry analysis deciphers the degradation products are biocompatible molecules like flavonoids and polyphenols. This study provides fundamental evidence and practical guidance for nanotechnology based on GO, including vaccine adjuvant, implantable devices, and energy storage.

Manganese/iron-based nanoprobes for photodynamic/chemotherapy combination therapy of tumor guided by multimodal imaging.

Early diagnosis of tumors is crucial in selecting appropriate treatment options to achieve the desired therapeutic effect, but it is difficult to accurately diagnose cancer by a single imaging modality due to technical constraints. Therefore, we synthesized a type of Fe3O4 nanoparticle with manganese dioxide grown on the surface and then prepared it by loading photosensitive drugs and traditional Chinese medicine monomers to create an integrated diagnosis/treatment multifunctional nanoplatform: Fe3O4@MnO2-celastrol (CSL)/Ce6. This nanoplatform can have full advantage of the tumor microenvironment (TME) characteristics of hypoxia (hypoxia), acidic pH (acidosis), and increased levels of reactive oxygen species (e.g., H2O2), even outside the TME. Specific imaging and drug release can also enhance tumor therapy by adjusting the hypoxic state of the TME to achieve the combined effect of chemotherapy (CT) and photodynamic therapy (PDT). Moreover, the obtained Fe3O4@MnO2-CSL/Ce6 has H2O2- and pH-sensitive biodegradation and can release the anticancer drug celastrol (CSL) and photosensitizer Ce6 in TME and simultaneously generate O2 and Mn2+. Therefore, the "dual response" synergistic strategy also confers specific drug release on nanomaterials, relieves tumor hypoxia and antioxidant capacity, and achieves significant optimization of CT and PDT. Furthermore, the resulting Mn2+ ions and Fe3O4 nanoparticles can be used for T1/T2 magnetic resonance imaging on tumor-bearing mice, and the released Ce6 can simultaneously provide fluorescence imaging functions. Therefore, Fe3O4@MnO2-CSL/Ce6 realized the synergistic treatment of PDT and CT under multimodal near-infrared fluorescence/photoacoustic (photoacoustic) imaging monitoring, showing its great potential in the accurate medical treatment of tumors.

Carbon nanocage-based nanozyme as an endogenous H2O2-activated oxygenerator for real-time bimodal imaging and enhanced phototherapy of esophageal cancer.

Intelligent phototherapy by theranostic nanosystems that can be activated by a tumor microenvironment has high sensitivity and specificity. However, hypoxia and low drug accumulation in tumors greatly limit its clinical application. Herein, we have designed a cage-like carbon-manganese nanozyme, which effectively relieves tumor hypoxia and delivers numerous photosensitizers (PSs) to the tumor site, for real-time imaging and enhanced phototherapy of esophageal cancer. Specifically, bovine serum albumin (BSA) was used as a template and reducing agent for preparing a BSA-MnO2 nanozyme; then a BSA-MnO2/IR820@OCNC (BMIOC) nanosystem was successfully synthesized by crosslinking BSA-MnO2 on the surface of IR820-loaded carboxylated carbon nanocages (OCNCs). Abundant PSs were successfully delivered to tumor sites via hollow OCNCs, and the final loading rate of IR820 reached 42.8%. The intratumor BMIOC nanosystem can be initiated by a tumor microenvironment to switch on its magnetic resonance (MR) imaging signal, and photothermal therapy (PTT) and photodynamic therapy (PDT) functions. Notably, the BSA-MnO2 nanozyme, with intrinsic catalase (CAT)-like activity, catalyzed endogenous H2O2 for oxygen generation to overcome tumor hypoxia and enhance PDT, thereby leading to more efficient therapeutic effects in combination with OCNC-elevated PTT. In addition, the H2O2-activated and acid-enhanced properties enable our nanosystem to be specific to tumors, protecting normal tissues from damage. By integrating a high drug loading capacity, a hypoxia regulation function, an enlarged phototherapy effect, and bimodal imaging into a nanozyme-mediated nanoreactor, this work realizes a "one for all" system and represents promising clinical translation for efficient esophageal cancer theranostics.

Targeted theranostics of lung cancer: PD-L1-guided delivery of gold nanoprisms with chlorin e6 for enhanced imaging and photothermal/photodynamic therapy.

Peptide modified nanoparticles have emerged as powerful tools for enhanced cancer diagnosis and novel treatment strategies. Here, human programmed death-ligand 1 (PD-L1) peptides were used for the first time for the modification of gold nanoprisms (GNPs) to enhance targeting efficiency. A multifunctional nanoprobe was developed that the GNPs@PEG/Ce6-PD-L1 peptide (GNPs@PEG/Ce6-P) was used for imaging-guided photothermal/photodynamic therapy by using the targeting effect of PD-L1. Both confocal imaging and flow cytometry experiments demonstrated a remarkable affinity of the as-prepared nanoprobes GNPs@PEG/Ce6-P to lung cancer cells (HCC827), which have a high PD-L1 expression. Subsequent in vitro and in vivo experiments further demonstrated that the nanoprobes GNPs@PEG/Ce6-P not only allowed for real-time visualization via fluorescence (FL) imaging and photoacoustic (PA) imaging, but also served as phototherapy agents for synergistic photothermal therapy (PTT) and photodynamic therapy (PDT). Furthermore, treatments on human lung cancer cells-derived tumors demonstrated that the nanoprobes GNPs@PEG/Ce6-P could significantly suppress tumor growth through PTT and PDT from GNPs and Ce6, respectively. In conclusion, the as-prepared new nanoprobes show promising potential for nanomedicine with remarkable targeting ability for dual-mode imaging and enhanced PDT and PTT effects on lung cancer.

Passion fruit-like exosome-PMA/Au-BSA@Ce6 nanovehicles for real-time fluorescence imaging and enhanced targeted photodynamic therapy with deep penetration and superior retention behavior in tumor.

Exosomes (Exos) of approximately 30-150 nm in diameters are the promising vehicles for therapeutic drugs. However, several challenges still exist in clinical applications, such as unsatisfied yield of exosomes, complicated labeling procedure and low drug loading efficiency. In this work, the gram-scale amount of high-purity urinary exosomes can be obtained from gastric cancer patients by non-invasive method. Passion fruit-like Exo-PMA/Au-BSA@Ce6 nanovehicles were fabricated by considerable freshly-urinary Exos loaded efficiently with multi-functionalized PMA/Au-BSA@Ce6 nanoparticles via instant electroporation strategy. In this system, prepared Exo-PMA/Au-BSA@Ce6 nanovehicles could be internalized into cancer cells effectively, and could delay the endocytosis of macrophages and prolong blood circulation time owing to its membrane structure and antigens. Under 633 nm laser irradiation and acidic condition, the structures of nanovehicles would be collapsed and tremendous PMA/Au-BSA@Ce6 nanoparticles could be released inside cancer cells, produced considerable singlet oxygen, inhibiting growth of tumor cells. In vivo experiment of MGC-803 tumor-bearing nude mice showed that prepared Exo-PMA/Au-BSA@Ce6 nanovehicles could target tumor cells with deep penetration and superior retention performance in tumors. This work reports a reliable conjugation-free labeling strategy for tracking exosomes harvested from human urine. Moreover, the integration of multifunctional nanoparticles with urinary Exos paves a versatile road for the development of cancer-targeted photodynamic therapy.

Effects of gold nanoprism-assisted human PD-L1 siRNA on both gene down-regulation and photothermal therapy on lung cancer.

Gold nanoprisms (GNPs) have been broadly studied for the potential applications in both imaging and treatment on tumors due to their special characteristics. Herein we reported that a new nanoplatform GNPs@PSS/PDADMAC-siRNA (GNPs-siRNA) was designed and fabricated by sequentially coating the GNPs with poly (sodium 4-styrenesulfonate) (PSS) and poly (-diallyldimethylammonium chloride) (PDADMAC) to carry small interfering RNA (siRNA). Human program death-ligand 1 (PD-L1) was recently known to be crucial for cancer cell survival through the intrinsic signaling activities, besides serving as an important checkpoint gene in immune system. We successfully attached the human PD-L1 siRNA to the surface of GNPs@PSS/PDADMAC to obtain the GNPs-hPD-L1 siRNA nanoplatform. Real Time Cellular Analysis (RTCA) assay demonstrated that GNPs-hPD-L1 siRNA exhibited remarkable capacity to inhibit the proliferation of human lung cancer cells. Subsequent in vitro and in vivo experiments verified that the GNPs-hPD-L1 siRNA not only functioned as a carrier for siRNA delivery to down-regulate the hPD-L1 expression, but also served for photoacoustic (PA) imaging and photothermal agents for photothermal therapy (PTT) in both human lung cancer cells and human lung cancer cells-derived tumors. Our findings could be expected to provide an innovative direction for future clinical transformation application. STATEMENT OF SIGNIFICANCE: To our knowledge, this is the first paper related to the hPD-L1 siRNA delivery combined with the gold nanoparticles, especially the gold nanoprisms. The as-prepared GNPs-hPD-L1 siRNA nanoplatform not only functioned as a carrier for siRNA delivery to down-regulate the PD-L1 expression, but also acted as photothermal agents for theranostic effects in both human lung cancer cells and human lung cancer cells-derived tumors. The as-prepared GNPs-hPD-L1 siRNA nanoplatform could knock down human PD-L1 gene expression, which caused the inhibition on proliferation of human lung cancer cell in vitro or in vivo. The as-prepared GNPs-hPD-L1 siRNA nanoplatform possessed excellent photoacoustic imaging ability and photothermal therapy effects.

A Nanoemulsion with A Porphyrin Shell for Cancer Theranostics.

A nanoemulsion with a porphyrin shell (NewPS) was created by the self-assembly of porphyrin salt around an oil core. The NewPS system has excellent colloidal stability, is amenable to different porphyrin salts and oils, and is capable of co-loading with chemotherapeutics. The porphyrin salt shell enables porphyrin-dependent optical tunability. The NewPS consisting of pyropheophorbide a mono-salt has a porphyrin shell of ordered J-aggregates, which produced a narrow, red-shifted Q-band with increased absorbance. Upon nanostructure dissociation, the fluorescence and photodynamic reactivity of the porphyrin monomers are restored. The spectrally distinct photoacoustic imaging (at 715 nm by intact NewPS) and fluorescence increase (at 671 nm by disrupted NewPS) allow the monitoring of NewPS accumulation and disruption in mice bearing KB tumors to guide effective photodynamic therapy. Substituting the oil core with Lipiodol affords additional CT contrast, whereas loading paclitaxel into NewPS facilitates drug delivery.

Carbon-gold hybrid nanoprobes for real-time imaging, photothermal/photodynamic and nanozyme oxidative therapy.

Rationale: Recently, there is one-fifth of human deaths caused by cancer, leading to cancer treatment remains a hard nut to crack in the medical field. Therefore, as an emerging diagnostic technology, mesoporous nanomaterials-based drug delivery systems integrated diagnosis and therapy have aroused tremendous interest owing to visually targeting effect and superior therapy efficacy compared with traditional cancer treatment. Methods: In this work, we have successfully synthesized mesoporous carbon-gold hybrid nanozyme nanoprobes, whereby mesoporous carbon nanospheres were doped with small gold nanoparticles (OMCAPs) and further stabilized with a complex of reduced serum albumin and folic acid (rBSA-FA). After loading IR780 iodide, the OMCAPs@ rBSA-FA@IR780 nanoprobes were finally accomplished for real-time imaging, photothermal/photodynamic and nanozyme oxidative therapy. Results: Herein, acid oxidized MCAPs possessed large surface area and numerous -COOH groups, which could be used to surface chemically modify numerous targeting molecules and load abundant NIR dye IR780, as well as be acted as photothermal reagents to enhance photothermal therapy effect. In addition, the small Au NPs embedded in OMCAPs were utilized as nanozyme to catalyze H2O2 located in tumor cells to generate ·OH for intracellular oxidative damage of tumor. Besides, as a commonly used near-infrared (NIR) fluorescence dye, the loaded IR780 iodide could not only apply for real-time imaging, but also effectively enhance photo-thermal therapy (PTT) upon the 808 nm laser irradiation. Moreover, FA molecules could enhance the targeted efficiency of the nanoprobes to the gastric tumor site. According to the systematical study in vitro and in vivo, our fabricated nanoprobes based on carbon-gold hybrid (OMCAPs@ rBSA-FA@IR780) revealed excellent tumor targeting efficacy, long tumor retention and favorably therapeutic effect for tumor. Conclusion: All the results demonstrated that here synthesized probes exhibited excellently diagnostic and therapeutic performance, indicating our technology may potentially offer an outstanding strategy for tumor-targeting theranostics.

Glutathione Induced Transformation of Partially Hollow Gold-Silver Nanocages for Cancer Diagnosis and Photothermal Therapy.

Gold-silver nanocages (GSNCs) are widely used in cancer imaging and therapy due to excellent biocompatibility, internal hollow structures, and tunable optical properties. However, their possible responses toward the tumor microenvironment are still not well understood. In this study, it is demonstrated that a kind of relatively small sized (35 nm) and partially hollow GSNCs (absorbance centered at 532 nm) can enhance the intrinsic photoacoustic imaging performances for blood vessels around tumor sites. More importantly, the high concentration of glutathione around the tumor cells' microenvironment may induce the aggregation, disintegration, and agglomeration of these GSNCs sequentially, allowing significant shifts in the absorbance spectrum of GSNCs to the near-infrared (NIR) region. This enhanced absorbance in the NIR region entails the significant photothermal therapy (PTT) effect. In vivo experiments, including photoacoustic microscopy (PAM) for cancer diagnosis and PTT in tumor model mice, also show coincident consequences. Taken together, the slightly hollow GSNCs may assist PAM-based tumor diagnosis and induce a tumor targeted PTT effect. This work paves a new avenue for the development of an alternative tumor diagnostic and therapeutic strategy.

Oral pH sensitive GNS@ab nanoprobes for targeted therapy of Helicobacter pylori without disturbance gut microbiome.

How to eradicate Helicobacter pylori (H. pylori) in vivo with antibiotic resistance owns tremendous clinical requirement. Herein, gold nanostars were conjugated with acid-sensitive cis-aconitic anhydride modified anti-H. pylori polyclonal antibodies, resultant pH sensitive gold nanostars@H. pylori-antibodies nanoprobes (GNS@Ab) were employed for the theranostics of H. pylori in vivo. Photoacoustic imaging confirmed that prepared GNS@Ab could target actively H. pylori in the stomach. GNS@Ab nanoprobes could kill H. pylori in vivo in model animals under NIR laser irradiation, all GNS@Ab nanoprobes could be excreted out of gut within 7 days after oral administration. Gastric local lesion caused by H. pylori restored to normal status within one month. GNS@Ab nanoprobes within therapeutic doses did not damage intestinal bacteria imbalance. Forty clinical specimens of H. pylori with antibiotic resistance were verified validity of GNS@Ab nanoprobes. Prepared oral pH-sensitive GNS@Ab nanoprobes own clinical translational potential in the theranostics of H. pylori in near future.

Matrix metallopeptidase 2 targeted delivery of gold nanostars decorated with IR-780 iodide for dual-modal imaging and enhanced photothermal/photodynamic therapy.

Nanotheranostics has gained increasing interest, as it offers a great potential to realize personalized diagnostics and therapy. In this work, we report a facile approach of the fabrication of gold nanostars (GNS) attached with matrix metalloproteinases (MMP2) polypeptides (Ac-GPLGIAGQ) and IR-780 iodide through bovine serum albumin (BSA) for targeted dual-modal photoacoustic (PA)/near-infrared (NIR) fluorescence imaging and enhanced photothermal therapy (PTT)/photodynamic therapy (PDT) for lung cancer. MMP2 polypeptides served as the targeting ligand, IR-780 iodide functioned as the NIR fluorescence imaging agent as well as PTT/PDT agent, and GNS acted as the carrier of IR-780 molecules and performed PA imaging and PTT. DLS and CCK-8 assay demonstrated that the nanoprobes (GNS@BSA/I-MMP2) exhibited excellent stability and biocompatibility under physiological conditions. Subsequent in vitro studies verified that GNS@BSA/I-MMP2 nanoparticles (NPs) were effectively internalized by A549 cancer cells and exhibited remarkable antitumor efficacy. Furthermore, GNS@BSA/I-MMP2 NPs could specifically target the tumor and significantly suppress the tumor growth, and their antitumor effects were mainly through the synergistic effects of PDT and PTT based on IR-780 and GNS. These findings imply the potential of GNS@BSA/I-MMP2 NPs as a targeting PA/NIR probe in tumor diagnosis and combined therapy with a single light source. STATEMENT OF SIGNIFICANCE: We reported a convenient and facile approach to load IR-780 iodides in gold nanostars (GNS). This material could simultaneously perform near-infrared imaging/photoacoustic imaging and thermotherapy/photodynamic therapy. MMP2 coating on the surface of GNS@BSA/IR-780 promoted the prepared nanoparticles (GNS@BSA/I-MMP2) to target the tumor region. The heat generated by the synergistic effect of the GNS and IR-780 molecules resulted in the high temperature of the GNS@BSA/I-MMP2 NPs, which efficiently suppressed the growth of tumor, and the tumor volume decreased by 93% compared with that in the PBS groups with laser irradiation.

Gastric Parietal Cell and Intestinal Goblet Cell Secretion: a Novel Cell-Mediated In Vivo Metal Nanoparticle Metabolic Pathway Enhanced with Diarrhea Via Chinese Herbs.

Up to date, the way in which metal nanoparticles are cleared in vivo has yet to be elucidated well. Herein, we report a novel intestinal goblet cell-mediated in vivo clearance pathway to remove metal nanoparticles. Typical metal nanoparticles such as triangular silver nanoplates, magnetic nanoparticles, gold nanorods, and gold nanoclusters were selected as representative examples. These metal nanoparticles were prepared, characterized, and injected via tail vein into a mice model with common bile duct (CBD) ligation. The feces and urines were collected for 7 days to be followed by the sacrifice of the mice and collection of the intestinal and gastric tissues for further analysis. The results showed that all four selected metal nanoparticles were located inside the goblet cells (GCs) of the whole intestinal tissue and were excreted into the gut lumen through the secretion of intestinal GC. Moreover, triangular silver nanoplates and gold nanorods were located inside the gastric parietal cells (PCs). Importantly, nanoparticles did not cause obvious pathological changes in intestinal tissues. In this study, we confirmed that the blood corpuscles are involved in the GCs secretion pathway. Furthermore, we found that the secretion of nanoparticles from intestinal GCs and PCs is accelerated by diarrhea induced via Chinese herbs. In conclusion, metal nanoparticles such as triangular silver nanoplates, magnetic nanoparticles, gold nanorods, and gold nanoclusters can be cleaned away by intestinal GCs and PCs. This novel pathway of in vivo clearance of metal nanoparticles has a great potential for future applications such as new drug design and development, nanoparticle-based labeling and in vivo tracking, and biosafety evaluation of in vivo nanoparticles.

Tumor-triggered drug release from calcium carbonate-encapsulated gold nanostars for near-infrared photodynamic/photothermal combination antitumor therapy.

Different stimulus including pH, light and temperature have been used for controlled drug release to prevent drug inactivation and minimize side-effects. Herein a novel nano-platform (GNS@CaCO3/ICG) consisting of calcium carbonate-encapsulated gold nanostars loaded with ICG was established to couple the photothermal properties of gold nanostars (GNSs) and the photodynamic properties of indocyanine green (ICG) in the photodynamic/photothermal combination therapy (PDT/PTT). In this study, the calcium carbonate worked not only a drug keeper to entrap ICG on the surface of GNSs in the form of a stable aggregate which was protected from blood clearance, but also as the a pH-responder to achieve highly effective tumor-triggered drug release locally. The application of GNS@CaCO3/ICG for in vitro and in vivo therapy achieved the combined antitumor effects upon the NIR irradiation, which was superior to the single PDT or PTT. Meanwhile, the distinct pH-triggered drug release performance of GNS@CaCO3/ICG implemented the tumor-targeted NIR fluorescence imaging. In addition, we monitored the bio-distribution and excretion pathway of GNS@CaCO3/ICG based on the NIR fluorescence from ICG and two-photon fluorescence and photoacoustic signal from GNSs, and the results proved that GNS@CaCO3/ICG had a great ability for tumor-specific and tumor-triggered drug release. We therefore conclude that the GNS@CaCO3/ICG holds great promise for clinical applications in anti-tumor therapy with tumor imaging or drug tracing.

Synergistic thermoradiotherapy based on PEGylated Cu3BiS3 ternary semiconductor nanorods with strong absorption in the second near-infrared window.

In this work, we report a successful synthesis of copper bismuth sulfide nanorods (NRs) with broad and strong photoabsorption ranging from ultraviolet (UV) to near-infrared (NIR) wavelengths, which can be used as a 1064 nm-laser-driven photothermal agent with the photothermal conversion efficiency of 40.7%, noticeably higher than most of the reported PTT agents working in NIR-II window. The as-prepared PEGylated Cu3BiS3 NRs were used as photoacoustic imaging (PAI) and CT imaging agents due to their strong NIR absorption and large X-ray attenuation coefficient of bismuth. We are the first to demonstrate that a small quantity of PEGylated Cu3BiS3 NRs in tumors can concentrate radiation energy and trigger mild PTT under NIR-II irradiation and thus, these particles could be used as a novel, synergistic thermoradiotheraputic agent that enhances the efficacy of radiotherapy.

Mitomycin C-treated human-induced pluripotent stem cells as a safe delivery system of gold nanorods for targeted photothermal therapy of gastric cancer.

Human-induced pluripotent stem cells (iPS) possess an intrinsic tumor tropism ability. However, iPS cells are impeded in clinical applications of tumor therapy due to the formation of teratomas and their survival in normal organs such as the liver, lungs, spleen and kidneys. Mitomycin C (MMC) can overcome this limitation by suppressing iPS proliferation. Herein, we fabricated a safe delivery system of iPS cells treated with MMC loading with gold nanorods (AuNRs) for the targeted photothermal treatment of gastric cancer. Our results showed that the tumor cells were efficiently killed by the heat generated from the gold nanorods, and the iPS cells ultimately died due to the action of MMC seven days after the photothermal treatment. This suggested that pre-treated iPS cells with MMC can be used as a novel and safe approach for targeted tumor therapy. This paves the road for clinical translation in the future.

Glucose-functionalized Au nanoprisms for optoacoustic imaging and near-infrared photothermal therapy.

Targeted imaging and tumor therapy using nanomaterials has stimulated research interest recently, but the high cytotoxicity and low cellular uptake of nanomaterials limit their bioapplication. In this paper, glucose (Glc) was chosen to functionalize Au nanoprisms (NPrs) for improving the cytotoxicity and cellular uptake of Au@PEG-Glc NPrs into cancer cells. Glucose is a primary source of energy at the cellular level and at cellular membranes for cell recognition. A coating of glucose facilitates the accumulation of Au@PEG-Glc NPrs in a tumor region much more than Au@PEG NPrs. Due to the high accumulation and excellent photoabsorbing property of Au@PEG-Glc NPrs, enhanced optoacoustic imaging of a tumor in vivo was achieved, and visualization of the tumor further guided cancer treatment. Based on the optical-thermal conversion performance of Au@PEG-Glc NPrs, the tumor in vivo was effectively cured through photothermal therapy. The current work demonstrates the great potential of Au@PEG-Glc NPrs in optoacoustic imaging and photothermal cancer therapy in future.

CD44v6 Monoclonal Antibody-Conjugated Gold Nanostars for Targeted Photoacoustic Imaging and Plasmonic Photothermal Therapy of Gastric Cancer Stem-like Cells.

Developing safe and effective nanoprobes for targeted imaging and selective therapy of gastric cancer stem cells (GCSCs) has become one of the most promising anticancer strategies. Herein, gold nanostars-based PEGylated multifunctional nanoprobes were prepared with conjugated CD44v6 monoclonal antibodies (CD44v6-GNS) as the targeting ligands. It was observed that the prepared nanoprobes had high affinity towards GCSC spheroid colonies and destroyed them completely with a low power density upon near-infrared (NIR) laser treatment (790 nm, 1.5 W/cm(2), 5 min) in vitro experiment. Orthotopic and subcutaneous xenografted nude mice models of human gastric cancer were established. Subsequently, biodistribution and photothermal therapeutic effects after being intravenously injected with the prepared nanoprobes were assessed. Photoacoustic imaging revealed that CD44v6-GNS nanoprobes could target the gastric cancer vascular system actively at 4 h post-injection, while the probes inhibited tumor growth remarkably upon NIR laser irradiation, and even extended survivability of the gastric cancer-bearing mice. The CD44v6-GNS nanoprobes exhibited great potential for applications of gastric cancer targeted imaging and photothermal therapy in the near future.

Enhanced bioavailability and efficiency of curcumin for the treatment of asthma by its formulation in solid lipid nanoparticles.

Curcumin has shown considerable pharmacological activity, including anti-inflammatory, but its poor bioavailability and rapid metabolization have limited its application. The purpose of the present study was to formulate curcumin-solid lipid nanoparticles (curcumin-SLNs) to improve its therapeutic efficacy in an ovalbumin (OVA)-induced allergic rat model of asthma. A solvent injection method was used to prepare the curcumin-SLNs. Physiochemical properties of curcumin-SLNs were characterized, and release experiments were performed in vitro. The pharmacokinetics in tissue distribution was studied in mice, and the therapeutic effect of the formulation was evaluated in the model. The prepared formulation showed an average size of 190 nm with a zeta potential value of -20.7 mV and 75% drug entrapment efficiency. X-ray diffraction analysis revealed the amorphous nature of the encapsulated curcumin. The release profile of curcumin-SLNs was an initial burst followed by sustained release. The curcumin concentrations in plasma suspension were significantly higher than those obtained with curcumin alone. Following administration of the curcumin-SLNs, all the tissue concentrations of curcumin increased, especially in lung and liver. In the animal model of asthma, curcumin-SLNs effectively suppressed airway hyperresponsiveness and inflammatory cell infiltration and also significantly inhibited the expression of T-helper-2-type cytokines, such as interleukin-4 and interleukin-13, in bronchoalveolar lavage fluid compared to the asthma group and curcumin-treated group. These observations implied that curcumin-SLNs could be a promising candidate for asthma therapy.

Folic acid-conjugated silica-modified gold nanorods for X-ray/CT imaging-guided dual-mode radiation and photo-thermal therapy.

Multifunctional nanoprobes are designed to own various functions such as tumor targeting, imaging and selective therapy, which offer great promise for the future of cancer prevention, diagnosis, imaging and treatment. Herein, silica was applied to replace cetyltrimethylammonium bromide (CTAB) molecules on the surface of gold nanorods (GNRs) by the classic Stöber method, thus eliminating their cytotoxicity and improving their biocompatibility. Folic acid molecule was covalently anchored on the surface of GNRs with silane coupling agent. The resultant folic acid-conjugated silica-modified GNRs show highly selective targeting, enhanced radiation therapy (RT) and photo-thermal therapy (PTT) effects on MGC803 gastric cancer cells, and also exhibited strong X-ray attenuation for in vivo X-ray and computed tomography (CT) imaging. In conclusion, the as-prepared nanoprobe is a good candidate with excellent imaging and targeting ability for X-ray/CT imaging-guided targeting dual-mode enhanced RT and PTT.