Detoxification of Organophosphate Poisoning Using Nanoparticle Bioscavengers.

Organophosphate poisoning is highly lethal as organophosphates, which are commonly found in insecticides and nerve agents, cause irreversible phosphorylation and inactivation of acetylcholinesterase (AChE), leading to neuromuscular disorders via accumulation of acetylcholine in the body. Direct interception of organophosphates in the systemic circulation thus provides a desirable strategy in treatment of the condition. Inspired by the presence of AChE on red blood cell (RBC) membranes, we explored a biomimetic nanoparticle consisting of a polymeric core surrounded by RBC membranes to serve as an anti-organophosphate agent.

D-SP5 Peptide-Modified Highly Branched Polyethylenimine for Gene Therapy of Gastric Adenocarcinoma.

Peptide-mediated targeting of tumors has become an effective strategy for cancer therapy. Retro-inverso peptides resist protease degradation and maintain their bioactivity. We used the retro-inverso peptide D(PRPSPKMGVSVS) (D-SP5) as a targeting ligand to develop gene therapy for gastric adenocarcinoma.

Toxins and derivatives in molecular pharmaceutics: Drug delivery and targeted therapy.

Protein and peptide toxins offer an invaluable source for the development of actively targeted drug delivery systems. They avidly bind to a variety of cognate receptors, some of which are expressed or even up-regulated in diseased tissues and biological barriers. Protein and peptide toxins or their derivatives can act as ligands to facilitate tissue- or organ-specific accumulation of therapeutics.

Conjugating influenza a (H1N1) antigen to n-trimethylaminoethylmethacrylate chitosan nanoparticles improves the immunogenicity of the antigen after nasal administration.

As one of the most serious infectious respiratory diseases, influenza A (H1N1) is a great threat to human health, and it has created an urgent demand for effective vaccines. Nasal immunization can induce both systemic and mucosal immune responses against viruses, and it can serve as an ideal route for vaccination. However, the low immunogenicity of antigens on nasal mucosa is a high barrier for the development of nasal vaccines.

Adding vitamin E-TPGS to the formulation of Genexol-PM: specially mixed micelles improve drug-loading ability and cytotoxicity against multidrug-resistant tumors significantly.

Genexol-PM, produced by Samyang Company (Korea) is an excellent preparation of paclitaxel (PTX) for clinical cancer treatment. However, it cannot resolve the issue of multidrug resistance (MDR)-a significant problem in the administration of PTX to cancer patients. To increase the efficacy of Genexol-PM against MDR tumors, a mixed micelle capable of serving as a vehicle for PTX was developed, and two substances were chosen as carrier materials: 1) Polyethylene glycol-polylactic acid (PEG-PLA), the original vehicle of Genexol-PM.

Linear-dendritic copolymer composed of polyethylene glycol and all-trans-retinoic acid as drug delivery platform for paclitaxel against breast cancer.

A new linear-dendritic copolymer composed of poly(ethylene glycol) (PEG) and all-trans-retinoic acid (ATRA) was synthesized as the anticancer drug delivery platform (PEG-G3-RA8). It can self-assemble into core-shell micelles with a low critical micelle concentration (CMC) at 3.48 mg/L.

Reversal of P-glycoprotein-mediated multidrug resistance by CD44 antibody-targeted nanocomplexes for short hairpin RNA-encoding plasmid DNA delivery.

Multidrug resistance (MDR) remains one of the major reasons for the reductions in efficacy of many chemotherapeutic agents in cancer therapy. As a classical MDR phenotype of human malignancies, the adenosine triphosphate binding cassette (ABC)-transporter P-glycoprotein (MDR1/P-gp) is an efflux protein with aberrant activity that has been linked to multidrug resistance in cancer. For the reversal of MDR by RNA interference (RNAi) technology, an U6-RNA gene promoter-driven expression vector encoding anti-MDR1/P-gp short hairpin RNA (shRNA) molecules was constructed (abbreviated pDNA-iMDR1-shRNA).

Recent advances in lymphatic targeted drug delivery system for tumor metastasis.

The lymphatic system has an important defensive role in the human body. The metastasis of most tumors initially spreads through the surrounding lymphatic tissue and eventually forms lymphatic metastatic tumors; the tumor cells may even transfer to other organs to form other types of tumors. Clinically, lymphatic metastatic tumors develop rapidly.

A D-peptide ligand of nicotine acetylcholine receptors for brain-targeted drug delivery.

Lysosomes of brain capillary endothelial cells are implicated in nicotine acetylcholine receptor (nAChR)-mediated transcytosis and act as an enzymatic barrier for the transport of peptide ligands to the brain. A D-peptide ligand of nAChRs (termed (D)CDX), which binds to nAChRs with an IC50 value of 84.5 nM, was developed by retro-inverso isomerization.

Tumor homing cell penetrating peptide decorated nanoparticles used for enhancing tumor targeting delivery and therapy.

Specific targeting ability and good tissue penetration are two critical requirements for tumor targeted delivery systems. Systematical selected peptides from a library may meet these two requirements. RLW was such a cell penetrating peptide that could specifically target to non-small cell lung cancer cells (A549).

Fluorescent carbonaceous nanospheres as biological probe for noninvasive brain imaging.

Fluorescent carbonaceous nanospheres (CDs) have generated much excitement in bioimaging because of their impressive fluorescent properties and good biocompatibility. In this study, we evaluated the potential application of CDs in noninvasive brain imaging. A new kind of CDs was prepared by a heat treating method using glutamic acid and glucose as the precursors.

Isomeric folate-conjugated polymeric micelles bind to folate receptors and display anticancer effects.

The present study aimed to prepare and evaluate polymeric micelles conjugated with folic acid through α- or γ-carboxyl groups for antitumor efficacy. The isomeric block copolymers, α- and γ-folate-polyethyleneglycol- distearoyl phosphatidylethanolamine (α- and γ-Fol-PEG-DSPE), were produced by solid phase peptide synthesis. Three types of doxorubicin (DOX)-loaded polymeric micelles (MPEG-DSPE-DOX and α- / γ-Fol-PEG-DSPE- DOX micelles) were prepared via the film formation method.

Enhancement in bioavailability of ketorolac tromethamine via intranasal in situ hydrogel based on poloxamer 407 and carrageenan.

The objective of this study was to construct a new in situ gel system based on the combination of poloxamer 407 and carrageenan (carrageenan-poloxamer 407 hydrogel, CPH) for intranasal delivery of ketorolac tromethamine. CPH showed potassium ion concentration - dependent erosion characteristics which ensured slow erosion in aqueous environment containing potassium ion at the physiological level. Loading with ketorolac tromethamine influenced erosion, drug release and thermosensitive properties of CPH.

The potential use of H102 peptide-loaded dual-functional nanoparticles in the treatment of Alzheimer's disease.

Alzheimer's disease (AD) is a complex neurodegenerative disease with few effective treatments. The non-targeted distribution of drugs decreases drug efficiency and cause side effects. The cascade targeting strategy has been suggested for precise drug delivery.

Angiopep-2 and activatable cell-penetrating peptide dual-functionalized nanoparticles for systemic glioma-targeting delivery.

Gliomas are hard to treat because of the two barriers involved: the blood-brain barrier and blood-tumor barrier. In this study, a dual-targeting ligand, angiopep-2, and an activatable cell-penetrating peptide (ACP) were functionalized onto nanoparticles for glioma-targeting delivery. The ACP was constructed by conjugating RRRRRRRR (R8) with EEEEEEEE through a matrix metalloproteinase-2 (MMP-2)-sensitive linker.

Antigen-conjugated N-trimethylaminoethylmethacrylate chitosan nanoparticles induce strong immune responses after nasal administration.

Purpose: Antigens were conjugated on the surface of N-trimethylaminoethylmethacrylate chitosan (TMC) nanoparticles to induce systemic and mucosal immune responses after nasal immunization.

Methods: TMC was synthesized by free radical polymerization and blank nanoparticles were prepared by ionic crosslinking of TMC and sodium tripolyphosphate. The model antigen (ovalbumin) was conjugated on the surface of blank nanoparticles (OVA-NP) through thioester bond formation.

Preparation and biological evaluation of photoluminescent carbonaceous nanospheres.

Carbon nanospheres (CNP) possess several unique properties that render CNP superior to traditional organic dyes and quantum dots in the biological application. However, the interaction of CNP with biological systems was far from well-known. In this study, a simple method using cocoon silk was used to synthesize photoluminescent CNP.

Brain tumor-targeted drug delivery strategies.

Despite the application of aggressive surgery, radiotherapy and chemotherapy in clinics, brain tumors are still a difficult health challenge due to their fast development and poor prognosis. Brain tumor-targeted drug delivery systems, which increase drug accumulation in the tumor region and reduce toxicity in normal brain and peripheral tissue, are a promising new approach to brain tumor treatments. Since brain tumors exhibit many distinctive characteristics relative to tumors growing in peripheral tissues, potential targets based on continuously changing vascular characteristics and the microenvironment can be utilized to facilitate effective brain tumor-targeted drug delivery.

Kidney-specific drug delivery system for renal fibrosis based on coordination-driven assembly of catechol-derived chitosan.

Renal fibrosis is a common progressive kidney disease, and there is a lack of efficient treatment for the condition. In this study, we designed a kidney-specific nanocomplex by forming coordination-driven assembly from catechol-derived low molecular weight chitosan (HCA-Chi), metal ions and active drug molecules. The coordination activities of various metals and ligands, cytotoxicity, immunogenicity and biodistribution of HCA-Chi were investigated.

In vitro, ex vivo, and in vivo evaluation of the effect of saturated fat acid chain length on the transdermal behavior of ibuprofen-loaded microemulsions.

In this study, the effect of the saturated fatty acid (FA) chain length in the oil phase on the behavior of Ibuprofen (IBU)-loaded transdermal microemulsion (ME) was evaluated in vitro, ex vivo, and in vivo. Three oils classified as long (LFA), medium (MFA), and short (SFA) chain length oils, Cremophor RH40 (surfactant) and Transcutol P (cosurfactant) were selected after experimental optimization. The physicochemical properties of ME were characterized, including IBU solubility in excipients, pseudo-ternary phase diagram construction, particle size, zeta potential, viscosity, and stability.

Preparation and evaluation of antigen/N-trimethylaminoethylmethacrylate chitosan conjugates for nasal immunization.

The frequent outbreak of respiratory infectious diseases such as influenza and pulmonary tuberculosis calls for new immunization strategies with high effectiveness. Nasal immunization is one of the most potential methods to prevent the diseases infected through the respiratory tract. In this study, we designed a water-soluble system based on antigen/N-trimethylaminoethylmethacrylate chitosan conjugates for nasal immunization.

Pretreatment with chemotherapeutics for enhanced nanoparticles accumulation in tumor: the potential role of G2 cycle retention effect.

Ligands were anchored onto nanoparticles (NPs) to improve the cell internalization and tumor localization of chemotherapeutics. However, the clinical application was shadowed by the complex preparation procedure and the immunogenicity and poor selectivity and stability of ligands. In this study, a novel strategy was developed to elevate the tumor cellular uptake and tumor localization of NPs utilizing the G2/M phase retention effect of docetaxel, one of the most common chemotherapeutics.

A simple one-step method for preparation of fluorescent carbon nanospheres and the potential application in cell organelles imaging.

Highly fluorescent carbon nanospheres with a quantum yield of 17.6% have been prepared by a one-step method with hydrothermal treatment of spider silk. Due to the high photostability, low toxicity and well blood compatibility, these carbon nanospheres could be used as an excellent probes for cancer cell imaging.

In vitro and in vivo intracellular distribution and anti-glioblastoma effects of docetaxel-loaded nanoparticles functioned with IL-13 peptide.

An active targeting delivery system helps increase intracellular drug delivery, which is promising for the treatment of glioblastoma. Interleukin 13 (IL-13) peptide which was derived from IL-13 protein could specially bind with IL-13Rα2, a receptor highly expressed on glioblastoma cells but not on normal brain cells, suggesting IL-13 peptide is an optional ligand for glioblastoma targeted therapy. In this contribution, IL-13 peptide was functionalized to nanoparticles (ILNP) to form a glioblastoma targeted drug delivery system where docetaxel was used as a model drug.