University of Central Florida Research Foundation Inc

Jesus Manuel Perez

Santimukul Santra

Sudip Nath

Atul Asati

Charalambos Kaittanis

Annette Khaled

Rania Bassiouni

Disclosed are compositions comprising polymeric nanoparticles and methods of using the same. The polymeric nanoparticles can be conjugated with a targeting ligand that is a substrate for a solid tumor-specific cell protein. The polymeric nanoparticles can also comprises an imaging compound and/or a therapeutic agent encapsulated in the hydrophobic interior of the nanoparticle. A cancer therapeutic composition comprising the nanoparticle is also disclosed. The disclosed nanoparticles can be used to target and deliver imaging and/or therapeutic compounds to cancer cells, thereby identifying and/or treating a solid tumor cell target. Methods for treating cancer, such as lung cancer, using the polymeric nanoparticles are also disclosed.

Bi-dota complex-loaded dendritic polymer nanoparticles

Disclosed herein are compositions comprising a CT20 peptide and methods of using the disclosed compositions to treat cancers expressing chaperonin containing TCP (CCT).

Method and compositions comprising a CT20 peptide

Methods, systems, compositions include biocompatible polymer coated nanoceria that function as aqueous redox catalyst with enhanced activity at an acidic to moderately alkaline pH value between 1 and 8. The compositions are used as oxidizing agents for decomposition, decontamination or 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 fluorescent probe in immunoassays and 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 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.

Oxidase activity of polymeric coated cerium oxide nano-particles

Bi-DOTA complex-loaded dendritic polymer nanoparticles

Differential surface-charge-dependent localization of nanoceria in normal cells and cancer cells plays a critical role in the toxicity profile of a nanoceria particle. Engineered surface-coated cerium oxide nanoparticles with different surface charges that are positive, negative and neutral provide therapeutic results for normal and cancer cell lines. Results show that nanoceria with a positive or neutral charge enters most of the cell lines studied, while nanoceria with a negative charge internalizes mostly in the cancer cell lines. Moreover, upon entry into the cells, nanoceria is localized to different cell compartments (e.g. cytoplasm and lysosomes) depending on the nanoparticle surface charge. The internalization and subcellular localization of nanoceria plays a key role in the nanoparticle cytotoxicity profile, exhibiting significant toxicity when they localize in the lysosomes of the cancer cell lines. In contrast, minimal toxicity is observed when they localize into the cytoplasm or do not enter the cells.

Differential tumor cell cytotoxicity via contact with coated cerium oxide nanoparticles

The invention discloses an aqueous method of making polymer coated superparamagnetic nanoparticles. Nanoparticles made by the method are included in the invention.

Aqueous method for making magnetic iron oxide nanoparticles

Methods, systems and compositions are disclosed wherein normal, non-transformed, healthy biological cells are protected from oxidative stress, radiation therapy and chemotherapy while diseased, transformed cells, such as, cancer cells, are provided no protection by the biocompatible, polymer coated nanoceria composition of the present invention. The polymer-coated nanoceria preparation herein exhibits no toxicity to normal cells and exhibits pH-dependent antioxidant properties at neutral or physiological pH values, between approximately 6.5 to approximately 11.0 and is inactive as an antioxidant at acidic pH values between approximately 2.0 to approximately 6.4. Improved therapeutic agents and cytoprotecting devices are based on the newly discovered, pH dependent properties of polymer-coated nanoceria that provide selective cytoprotection.

Polymer coated ceria nanoparticles for selective cytoprotection

Aqueous method of making magnetic iron oxide nanoparticles

A 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. Embodiment one is a two-chamber 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 a fluorophore capable of fluorescence emission, a chemiluminescent agent, a magnetic relaxation agent and an X-ray contrast agent. Embodiment two is a single chamber device consisting of a multifunctional nanocomposite with a ROS-scavenging nanoparticle constituent (nanoceria) and a multimodal reporting nanoparticle component (i.e. Dex-IO-DiR). The device and system are utilized in treatment of diseases with a pro-inflammatory component, including, but not limited to, Crohn's disease, ulcerative colitis, inflammatory bowel disease, cystic fibrosis, arthritis, and cancer chemotherapy.

Cerium oxide nanoparticle-based device for the detection of reactive oxygen species and monitoring of chronic inflammation

Cerium-oxide nanoparticle based device for the detection of reactive oxygen species and monitoring of chronic inflammation

The invention discloses an aqueous method of making polymer coated superparamagnetic nanoparticles. The method comprises providing a mixture of iron salts in an aqueous solution of hydrochloric acid. A solution of ammonium hydroxide is added to the mixture and stirred. Stirring continues with an aqueous solution of one or more biocompatible polymers so as to promote formation of polymer coated iron nanoparticles in suspension, wherein optionally at least one of the polymers in the coating may be aminated. Centrifuging the suspension leaves a supernatant without large particles. Filtering the supernatant through an ultrafiltration membrane and collecting the filtrate recovers polymer coated nanoparticles. Crosslinking the polymer is effected by treatment with a solution of epichlorohydrin and sodium hydroxide while stirring vigorously for up to about eight hours. Optionally aminating the polymer may be accomplished by treatment with ammonia after crosslinking and then removing remaining free epichlorohydrin. Nanoparticles made by the method are included in the invention.

Procedures and methods for synthesizing biodegradable polymer coated nanoceria result in stable nanoparticle preparations in aqueous systems and physiological relevant colloidal solutions, such as phosphate buffer saline. The coated nanoceria preparations increase the nanoparticle concentration in aqueous or colloidal solutions as most needed for antioxidant, free-radical scavenger, and autocatalytic biomedical applications, including, biological, pharmacological and potential clinical use. To meet this need, a facile synthetic procedure for preparation of a biodegradable polymer-coated nanoceria is disclosed; the preferred biodegradable polymer is dextran. The synthesis method occurs under ambient conditions in an aqueous phase without the use of surfactants and results in a monodispersed preparation that is dextran-coated as determined by dynamic light scattering (DLS). Preliminary characterization of polymer coated nanoceria by XPS, TEM, XRD, and the like shows that these nanoparticles have the necessary physical properties for the desired biological potency, such as Ce/Cemixed valence state.

Growing community of inventors

Orlando, FL, United States of America

Jesus Manuel Perez