Tumor-Targeting Glycol Chitosan Nanoparticles for Image-Guided Surgery of Rabbit Orthotopic VX2 Lung Cancer.

Theranostic nanoparticles can deliver therapeutic agents as well as diverse imaging agents to tumors. The enhanced permeation and retention (EPR) effect is regarded as a crucial mechanism for the tumor-targeted delivery of nanoparticles. Although a large number of studies of the EPR effect of theranostic nanoparticles have been performed, the effect of the change in the body size of the host on the EPR effect is not fully understood.

Caspase-3/-7-Specific Metabolic Precursor for Bioorthogonal Tracking of Tumor Apoptosis.

Apoptosis is one of the most important intracellular events in living cell, which is a programmed cell death interrelated with caspase enzyme activity for maintaining homeostasis in multicellular organisms. Therefore, direct apoptosis imaging of living cells can provide enormous advantages for diagnosis, drug discovery, and therapeutic monitoring in various diseases. However, a method of direct apoptosis imaging has not been fully validated, especially for live cells in in vitro and in vivo.

Piperlongumine inhibits TGF-β-induced epithelial-to-mesenchymal transition by modulating the expression of E-cadherin, Snail1, and Twist1.

Cancer is a life-threatening disease, and the occurrence of metastasis, which increases the lethality of primary tumors, is increasing. The epithelial-to-mesenchymal transition (EMT) is a biological process by which epithelial cells lose cell-cell adhesion properties and acquire mesenchymal properties, including motility and invasiveness. EMT is considered an early stage of metastasis; therefore, inhibiting EMT may be an effective anticancer therapy.

Formulation and Evaluation of a Self-microemulsifying Drug Delivery System Containing Bortezomib.

The purposes of the present study were to develop a self-microemulsifying drug delivery system (SMEDDS) containing bortezomib, a proteasome inhibitor. The solubility of the drug was evaluated in 15 pharmaceutical excipients. Combinations of oils, surfactants and cosurfactants were screened by drawing pseudo-ternary phase diagrams.

Photosensitizer-loaded bubble-generating mineralized nanoparticles for ultrasound imaging and photodynamic therapy.

In this work, we have developed photosensitizer-loaded bubble-generating calcium carbonate (CaCO)-mineralized nanoparticles that have potential for ultrasound imaging (US)-guided photodynamic therapy (PDT) of tumors. A photosensitizer, chlorin e6 (Ce6)-loaded CaCO-mineralized nanoparticles (Ce6-BMNs), was prepared using an anionic block copolymer-templated in situ mineralization method. Ce6-BMNs were composed of the Ce6-loaded CaCO core and the hydrated poly(ethylene glycol) (PEG) shell.

Shikonin as an inhibitor of the LPS-induced epithelial-to-mesenchymal transition in human breast cancer cells.

Shikonin (SK), a natural naphthoquinone isolated from the Chinese medicinal herb, has been known to suppress the proliferation of several cancer cells. However, its role in the epithelial mesenchymal transition (EMT) has yet to be demonstrated. The aim of the present study was to examine the effects of SK on EMT.

Shikonin causes apoptosis by up-regulating p73 and down-regulating ICBP90 in human cancer cells.

Shikonin, a natural naphthoquinone isolated from the Chinese traditional medicine Zi Cao (purple gromwell), is known to suppress the growth of several cancer cell types. In this study, we evaluated the pro-apoptotic effects of shikonin on MCF-7 and HeLa cells, and investigated the underlying mechanism. Shikonin-induced apoptosis was associated with activation of caspase-3, poly(ADP-ribose) polymerase (PARP) cleavage, up-regulation of p73, and down-regulation of BCL-2.

Antibacterial Nanofibrous Mats Composed of Eudragit for pH-Dependent Dissolution.

A pH-responsive nanofibrous mesh was prepared for the controlled release of antibiotics in response to pH changes. Eudragit EPO (EPO) and Eudragit L100 (L100) were injected through inner and outer needle and simultaneously electrospun through coaxial nozzles composed of inner and outer needles. Various amounts of EPO and L100 were coejected with tetracycline through the needle and simultaneously electrospun to the fibrous meshes.

Optimization of the surface immobilized folate on the magnetic nanoparticles.

Cancer cells overexpressing folate receptors have been targeted using a folate decorated carriers for anti-cancer drugs in aims to overcome the tissue non-specificity of anti-cancer agents. We here prepared magnetic nanoparticles and surface-decorated them with different amounts of folate to optimize the number of the immobilized folate on the carriers for superior targeting effects. Magnetic nanoparticles were prepared by oxidizing ferric or ferrous chloride solution to iron oxide in the presence of poly(vinyl alcohol).

Cancer-targeted MDR-1 siRNA delivery using self-cross-linked glycol chitosan nanoparticles to overcome drug resistance.

P-glycoprotein (Pgp) mediated multi-drug resistance (MDR) is a major cause of failure in chemotherapy. In this study, small interfering RNA (siRNA) for Pgp down-regulation was delivered to tumors to overcome MDR in cancer. To achieve an efficient siRNA delivery in vivo, self-polymerized 5'-end thiol-modified siRNA (poly-siRNA) was incorporated in tumor targeting glycol chitosan nanoparticles.

Shikonin blocks migration and invasion of human breast cancer cells through inhibition of matrix metalloproteinase-9 activation.

Shikonin, a natural naphthoquinone isolated from a traditional Chinese medicinal herb, has been reported to promote tumor cell death. However, there are few reports concerning its effect on metastasis-related cell invasion and migration behavior. In the present study, we investigated the effect of shikonin on human breast cancer invasion and migration.

DNA amplification in neutral liposomes for safe and efficient gene delivery.

In general, traditional gene carriers contain strong cationic charges to efficiently load anionic genes, but this cationic character also leads to destabilization of plasma membranes and causes severe cytotoxicity. Here, we developed a PCR-based nanofactory as a safe gene delivery system. A few template plasmid DNA can be amplified by PCR inside liposomes about 200 nm in diameter, and the quantity of loaded genes highly increased by more than 8.

pH-responsive robust polymer micelles with metal-ligand coordinated core cross-links.

We report on pH-responsive core-shell polymer micelles with catechol-Fe(3+) coordinated core cross-links, which provide robustness to drug-loaded polymer micelles and allow the facilitated intracellular release of loaded anticancer drugs in response to an endosomal acidic pH.

Cell labeling and tracking method without distorted signals by phagocytosis of macrophages.

Cell labeling and tracking are important processes in understanding biologic mechanisms and the therapeutic effect of inoculated cells in vivo. Numerous attempts have been made to label and track inoculated cells in vivo; however, these methods have limitations as a result of their biological effects, including secondary phagocytosis of macrophages and genetic modification. Here, we investigated a new cell labeling and tracking strategy based on metabolic glycoengineering and bioorthogonal click chemistry.

Shikonin inhibits the growth of human prostate cancer cells via modulation of the androgen receptor.

Shikonin, a natural naphthoquinone isolated from the traditional Chinese medicine Zi Cao (gromwell), has been shown to possess tumor cell killing activity. The human androgen receptor (AR) is a nuclear transcription factor that serves as a major therapeutic target for prostate cancer. However, AR regulation by shikonin has not been reported.

Chemical tumor-targeting of nanoparticles based on metabolic glycoengineering and click chemistry.

Tumor-targeting strategies for nanoparticles have been predominantly based on optimization of physical properties or conjugation with biological ligands. However, their tumor-targeting abilities remain limited and insufficient. Furthermore, traditional biological binding molecules have intrinsic limitations originating from the limited amount of cellular receptors and the heterogeneity of tumor cells.

Non-invasive optical imaging of cathepsin B with activatable fluorogenic nanoprobes in various metastatic models.

An increasing number of treatments of metastases rely on diagnostics and imaging these days. The facts that the activity of cathepsin B (CB) is markedly linked to the metastatic process and that CB is found highly expressed in the pericellular regions in this process make CB an attractive target for diagnosing metastases. We have developed a CB-sensitive nanoprobe (CB-CNP) consisting of self-quenched CB-sensitive fluorogenic peptide probes conjugated onto the surface of tumor-targeting glycol chitosan nanoparticles (CNPs).

Tumor-targeting transferrin nanoparticles for systemic polymerized siRNA delivery in tumor-bearing mice.

Transferrin (TF) is widely used as a tumor-targeting ligand for the delivery of anticancer drugs because the TF receptor is overexpressed on the surface of various fast-growing cancer cells. In this article, we report on TF nanoparticles as an siRNA delivery carrier for in vivo tumor-specific gene silencing. To produce siRNA carrying TF nanoparticles (NPs), both TF and siRNA were chemically modified with sulfhydryl groups that can build up self-cross-linked siRNA-TF NPs.

Self-crosslinked human serum albumin nanocarriers for systemic delivery of polymerized siRNA to tumors.

The safe and effective systemic delivery of siRNA is a prerequisite for the successful development of siRNA-based cancer therapeutics. For the enhanced delivery of siRNA, cationic lipids and polymers have been widely used as siRNA carriers to form electrolyte complexes with anionic siRNA. However, the considerable toxicity of strong cationic-charged molecules hampers their clinical use.

Calcium phosphate-reinforced photosensitizer-loaded polymer nanoparticles for photodynamic therapy.

Calcium phosphate-reinforced photosensitizer-loaded polymer nanoparticles have been developed for photodynamic therapy. Chlorin e6 (Ce6)-loaded core-shell-corona polymer micelles of poly(ethylene glycol)-b-poly(L-aspartic acid)-b-poly(L-phenylalanine) (PEG-PAsp-PPhe) were employed as template nanoparticles for mineralization with calcium phosphate (CaP). CaP deposition was performed by the electrostatic localization of calcium ions at the anionic PAsp middle shells and the subsequent addition of phosphate anions.

Enhanced drug-loading and therapeutic efficacy of hydrotropic oligomer-conjugated glycol chitosan nanoparticles for tumor-targeted paclitaxel delivery.

Enhanced drug-loading and therapeutic efficacies are highly essential properties for nanoparticles as tumor-targeting drug carriers. Herein, we developed the glycol chitosan nanoparticles with hydrotropic oligomers (HO-CNPs) as a new tumor targeting drug delivery system. For enhancing drug-loading efficiency of paclitaxel in drug carriers, hydrotropic 2-(4-(vinylbenzyloxy)-N,N-diethylnicotinamide) (VBODENA-COOH) oligomers, that were used for enhancing the aqueous solubility of paclitaxel, were directly conjugated to glycol chitosan polymers.

Biocompatible glycol chitosan-coated gold nanoparticles for tumor-targeting CT imaging.

Purpose: The application of gold nanoparticles (AuNPs) in biomedical field was limited due to the low stability in the biological condition. Herein, to enhance stability and tumor targeting ability of AuNPs, their surface was modified with biocompatible glycol chitosan (GC) and the in vivo biodistribution of GC coated AuNPs (GC-AuNPs) were studied through computed tomography (CT).

Methods: Polymer-coated gold nanoparticles were produced using GC as a reducing agent and a stabilizer.

Ischemic brain imaging using fluorescent gold nanoprobes sensitive to reactive oxygen species.

Fluorescein-labeled hyaluronic acids (HA) were immobilized on gold nanoparticles for reactive oxygen species (ROS) detection. The efficacy of HA immobilized gold nanoparticles (HHAuNPs) was evaluated in a stroke animal model. The stroke rat model was produced by transient middle cerebral artery occlusion (MCAO), which induced transient ischemia and reperfusion (I/R) in the brain.