Synthesis of Hyperbranched Amphiphylic Polyester and Theranostic Nanoparticles thereof

A method of making a hyperbranched amphiphillic polyester compound includes drying under vacuum a mixture of 2-(4-hydroxybutyl)-malonic acid and p-toulene sulphonic acid as a catalyst. The vacuum is then released with a dry inert gas after drying. The dried mixture is heated under the inert gas at a temperature sufficient for polymerization. The inert gas is evacuated while continuing to heat the mixture. The formed polymer is then dissolved in dimethylformamide and precipitated out by adding methanol. Modifications of the method yield nanoparticles of polyesters having properties suited for coencapsulating fluorescent dyes together with therapeutic drugs, resulting in theranostic nanoparticles, that is, nanoparticles useful in both therapeutic treatments and diagnostics methods

Synthesis of hyperbranched amphiphylic polyester and theranostic nanoparticles thereof

A method of making a hyperbranched amphiphillic polyester compound includes drying under vacuum a mixture of 2-(4-hydroxybutyl)-malonic acid and p-toulene sulphonic acid as a catalyst. The vacuum is then released with a dry inert gas after drying. The dried mixture is heated under the inert gas at a temperature sufficient for polymerization. The inert gas is evacuated while continuing to heat the mixture. The formed polymer is then dissolved in dimethylformamide and precipitated out by adding methanol. Modifications of the method yield nanoparticles of polyesters having properties suited for coencapsulating fluorescent dyes together with therapeutic drugs, resulting in theranostic nanoparticles, that is, nanoparticles useful in both therapeutic treatments and diagnostics methods

Multimodal, Multifunctional Polymer Coated Nanoparticles

Disclosed are nanoparticles having a metallic core consisting essentially of superparamagnetic iron oxide: a polymeric coat surrounding said core, the coat having a matrix of polyacrylic acid and forming an outer periphery of said nanoparticle; a pleurality of hydrophobic pockets formed by the polymeric coat; a plurality of carboxylic groups along an outer periphery of the polymeric coat and effective to conjugate with a predeterminded targeting ligand which functionalizes the nanoparticle; a lipophylic fluorescent dye encapsulated in the pleurality of hydrophobix pockets. Associated methods of making the nanoparticles and of treatments using the nanoparticles are also disclosed

Activatable MR Prodrug for Targeted Delivery and Treatment of Cancer

In this study, a new multimodal theranostic tool is reported utilizing nanoceria delivery system conjugated with the ICAM1 antibody and a magnetic resonance (MR) probe as a prodrug with both MR and cytotoxic properties. The prodrug was synthesized from doxorubicin and phenyl-amine modified DTPA chelated with gadolinium utilizing dithiobis(succinimidyl propionate) (DSP) as a crosslinker. Nanoceria was synthesized from cerium oxide and polyacrylic acid using a water-based alkali precipitation technique. Doxorubicin and the synthesized prodrug were encapsulated separately within the nanoceria polymer matrix using a solvent diffusion method. The drug/prodrug-encapsulated nanoceria’s carboxylated surface was functionalized with the ICAM1 antibody utilizing EDC/NHS chemistries and the resulting formulations were purified and characterized by DLS, zeta potential, UV/Vis, and MR. The efficacy of this platform was measured by treating MDA-MB-231 breast cancer (TNBC) cells and MCF-7 cells with the drug/prodrug-loaded, ICAM1-conjugated nanoceria and analyzing the results of the treatment. Results were evaluated by cytotoxicity assays (MTT), fluorescence microscopy, reactive oxygen species determination, and comet assays. In all, the results show the nanoceria platform is target-specific to TNBC, and the encapsulated prodrug is able to be activated releasing doxorubicin and initiating apoptosis in an in vivo breast cancer model

Cerium-Oxide-Nanoparticle-Based Device for the Detection of Reactive Oxygen Species and Monitoring of Chronic Inflammation DIV

polymer-coated cerium oxide based device and system is disclosed for detecting reactive oxygen species and monitoring chronic inflammation. The device and system encapsulate free therapeutic nanoparticle elements not present in a living body in a prosthetic or implantable unit. In one embodiment, the unit is a structure with a reactive oxygen species (ROS) scavenging component on one end and at the opposite end is an imaging agent consisting of at least one of the fluorophore capable of fluorescence emission, a chemiluminescent agent, a magnetic relaxation agent and an X-ray contrast agent. In a second embodiment, a single chamber device consisting of a multifunctional nanocomposite has a ROS-scavenging nanoparticle constituent (nanoceria) and a multimodal reporting nanoparticle component (i.e. Dex-IR-DiR). The device and system is utilized in treatment of diseases with a pro-inflammatory component, including, but not limited to, Crohn\u27s disease, ulcerative colitis, inflammatory bowel disease, cystic fibrosis, arthritis, and cancer chemotherapy

Oxidase Activity of Polymeric Coated Cerium Oxide Nanoparticles

methods, systems, compositions include biocompatible polymer coated nanoceria that function as aqeous redox catalyst with enhanced activity at an acidic to moderaly alkaline pH value between 1 and 8. The compositions are used as oxidizing agents for decompostion, decontamination and inactivation of organic contaminants, such as, pesticides and chemical warfare agents. Another use includes nanoceria as targetable nanocatalyst prepared by conjugating various targeting ligands to the nanoparticle coating to form a colorimetric or fuorescent probe in immunoassays or other molecule binding assays that involve the use of a molecule in solution that changes the color of the solution or emits a fluorescent signal, where localization of the nanoceria to organs or tissue is assessed by treatment with an oxidation sensitive dye or other detection devices. Versatility and uses of the nanoceria compositions are controlled by pH value, choice of dye substrate and thickness of the polymer coating on the ceria nanoparticles

Detection of Food-Borne Pathogens Using Nanozyme Technology

The recurrent outbreak of E. coli necessitates the need of rapid and sensitive technology to detect bacteria in the food samples. E. coli O157:H7 is infectious at very low CFU counts (10-100 viable cells). Herein, we report a unique combination of magnetic and plasmonic properties in a single nanoplatform, which have superior peroxidase-like activity. This new nanosensor platform, magneto-plasmonic nanosensor (MPnS), is composed of superparamagnetic iron oxide nanoparticles (IONPs) and gold nanoparticles (GNPs) and stabilized with polyacrylic acid polymer, providing surface -COOH functional groups. By using EDC/NHS bioconjugation chemistry, the surface of MPnS is decorated with E. coli O157:H7-specific antibodies. We compared the catalytic activities of MPnS with that of GNPs, IONPs and traditional HRP and calculated Michaelis-Menten kinetics, which showed highest catalytic activity for MPnS. The ELISA-like experiments were performed using MPnS to detect E. coli within 30 min with higher sensitivity. We extended this detection study using milk and spinach samples. Various spectrophotometric and colorimetric experimental results in the specific detection of E. coli will be detailed in this presentation

Rapid and Sensitive Detection of an Intracellular Pathogen in Human Peripheral Leukocytes with Hybridizing Magnetic Relaxation Nanosensors

Bacterial infections are still a major global healthcare problem. The quick and sensitive detection of pathogens responsible for these infections would facilitate correct diagnosis of the disease and expedite treatment. Of major importance are intracellular slow-growing pathogens that reside within peripheral leukocytes, evading recognition by the immune system and detection by traditional culture methods. Herein, we report the use of hybridizing magnetic nanosensors (hMRS) for the detection of an intracellular pathogen, Mycobacterium avium spp. paratuberculosis (MAP). The hMRS are designed to bind to a unique genomic sequence found in the MAP genome, causing significant changes in the sample’s magnetic resonance signal. Clinically relevant samples, including tissue and blood, were screened with hMRS and results were compared with traditional PCR analysis. Within less than an hour, the hMRS identified MAP-positive samples in a library of laboratory cultures, clinical isolates, blood and homogenized tissues. Comparison of the hMRS with culture methods in terms of prediction of disease state revealed that the hMRS outperformed established culture methods, while being significantly faster (1 hour vs 12 weeks). Additionally, using a single instrument and one nanoparticle preparation we were able to detect the intracellular bacterial target in clinical samples at the genomic and epitope levels. Overall, since the nanoparticles are robust in diverse environmental settings and substantially more affordable than PCR enzymes, the potential clinical and field-based use of hMRS in the multiplexed identification of microbial pathogens and other disease-related biomarkers via a single, deployable instrument in clinical and complex environmental samples is foreseen

Innovative Anti-Oxidant Nanoceria for early Early Diagnosis and Treatment of Lung Cancer

Cerium oxide nanoparticles (nanoceria, NC) has emerged as an important nanomaterial due to its 1) unique redox property of switching oxidation states between Ce3+ and Ce4+ depending upon the environment and 2) higher surface to volume ratio for better oxygen exchange and higher reactivity. Over the past decade, these exceptional redox properties of NC were extensively used in various biological studies including neuroprotective, anti-inflammatory, anti-aging, cardio protection and other oxidative-stress related complications. In addition, the anti-oxidant NC showed exceptional anti-tumor activity when incubated with carcinomas. According to the American Cancer Society 1,665,540 new cases of cancer and 585,720 deaths were reported in 2014. Non-Small-Cell Lung Cancer (NSCLC) is a major cause of death amongst smokers. Nanotechnology in cancer therapy has earned popularity because of their potential to cross biological barriers and to deliver therapeutic drugs specifically to the disease site in higher concentrations. We have discovered novel polyacrylic acid-coated functional NC for the targeted diagnosis and treatment of lung cancers. In this study, we have designed NC-based theranostics to be used as personalized nanomedicine specifically for the heavy smokers. Combination therapy was used to deliver two therapeutic drugs, doxorubicin and Hsp90 inhibitor Ganetespib for the effective treatment of lung cancer. In this project, we have introduced an innovative nanotechnology for the timely detection and simultaneous delivery of two therapeutic drugs to the lung cancer cells. The surface functional groups of NC were decorated with folic acid to target folate-receptor over-expressing A549 lung cancer cells. Experimental results showed more than 80% cell death within 24 h of incubation using drugs-encapsulating NC-based nanotheranostics. Detailed synthesis protocols, cytotoxicity, controlled drug release and microscopic results will be discussed in this presentation

Selective N -Alkylation Of Β-Alanine Facilitates The Synthesis Of A Poly(Amino Acid)-Based Theranostic Nanoagent

The development of functional amino acid-based polymeric materials is emerging as a platform to create biodegradable and nontoxic nanomaterials for medical and biotechnology applications. In particular, facile synthetic routes for these polymers and their corresponding polymeric nanomaterials would have a positive impact in the development of novel biomaterials and nanoparticles. However, progress has been hampered by the need to use complex protection-deprotection methods and toxic phase transfer catalysts. In this study, we report a facile, single-step approach for the synthesis of an N-alkylated amino acid as an AB-type functional monomer to generate a novel pseudo-poly(amino acid), without using the laborious multistep, protection-deprotection methods. This synthetic strategy is reproducible, easy to scale up, and does not produce toxic byproducts. In addition, the synthesized amino acid-based polymer is different from conventional linear polymers as the butyl pendants enhance its solubility in common organic solvents and facilitate the creation of hydrophobic nanocavities for the effective encapsulation of hydrophobic cargos upon nanoparticle formation. Within the nanoparticles, we have encapsulated a hydrophobic DiI dye and a therapeutic drug, Taxol. In addition, we have conjugated folic acid as a folate receptor-targeting ligand for the targeted delivery of the nanoparticles to cancer cells expressing the folate receptor. Cell cytotoxicity studies confirm the low toxicity of the polymeric nanoparticles, and drug-release experiments with the Taxol-encapsulated nanoparticles only exhibit cytotoxicity upon internalization into cancer cells expressing the folate receptor. Taken together, these results suggested that our synthetic strategy can be useful for the one-step synthesis of amino acid-based small molecules, biopolymers, and theranostic polymeric nanoagents for the targeted detection and treatment of cancer. © 2011 American Chemical Society