University of California

Northwestern University

Andre E Nel

Huan Meng

Jeffrey I Zink

Xiangsheng Liu

Monty Liong

Tian Xia

Mark C Hersam

Nikhita Mansukhani

Fuyuhiko Tamanoi

Linda M Guiney

Jie Lu

Ruibin Li

Zongxi Li

Min Xue

Kuo-Ching Mei

Zhaoxia Ji

Derrick Y Tarn

Sanaz Gardner

In order to facilitate the approval and commercialization of silicasome drug delivery systems (e.g. irinotecan silicasomes) it is necessary to scale up synthesis of the drug-loaded silicasomes. In this regard, it was discovered that the synthesis protocols used for laboratory synthesis of drug-loaded silicasomes (e.g., 500 mg/batch) do not scale to large scale silicasome production, because the resulting products were too heterogeneous for use as pharmaceuticals. Accordingly, new methods are provided herein that effectively afford the large-scale production of mesoporous silica nanoparticles (MSNPs) and lipid bilayer coated MSNPs (silicasomes).

Scale up synthesis of silicasome nanocarriers

A nanocarrier including a silica body having a surface and defining a plurality of pores that are suitable to receive molecules therein is described. The nanocarrier also includes a lipid bilayer coating the surface, and a cargo-trapping agent within the phospholipid bilayer. The phospholipid bilayer stably seals the plurality of pores. The cargo-trapping reagent can be selected to interact with a desired cargo, such as a drug.

Mesoporous silica nanoparticles with lipid bilayer coating for cargo delivery

In various embodiments functionalized graphene oxide(s) are provided that demonstrate improved antimicrobial activity, where the graphene oxide(s) are functionalized to increase carbon radical (·C) density.

Identification and optimization of carbon radicals on hydrated graphene oxide for ubiquitous antibacterial coatings

A submicron structure comprising a silica body defining a plurality of pores that are suitable to receive molecules therein, and having a surface, and a phospholipid bilayer coating the surface, wherein said submicron structure has a maximum dimension of less than one micron, and wherein the phospholipid bilayer stably seals the plurality of pores; and wherein the submicron structure is a member of a monodisperse population of submicron structures.

Lipid bilayer coated mesoporous silica nanoparticles with a high loading capacity for one or more anticancer agents

In certain embodiments a platform technology for the facilitating immune therapy in the treatment of cancer is provided. In certain embodiments nanocarriers are provided that facilitate delivery of an IDO inhibitor in conjunction with an inducer of cell death (ICD-inducer). In certain embodiments the IDO inhibitor is conjugated to a component of a lipid bilayer forming a nanovesicle. In still another embodiment, methods and compositions are provided where an ICD-inducing agent (e.g., doxorubicin, oxaliplatin, mitoxantrone etc.) and an IDO pathway inhibitor (e.g., an IDO inhibitor-prodrug) are integrated into a nanocarrier (e.g. a lipid-bilayer (LB)-coated nanoparticle), that allows systemic delivery to orthotopic pancreatic cancer site.

Nano-enabled immunotherapy in cancer

In various embodiments functionalized graphene oxide(s) are provided that demonstrate improved antimicrobial activity, where the graphene oxide(s) are functionalized to increase carbon radical (.C) density.

Mesoporous silica nanoparticles with a lipid bilayer coating for cargo delivery

A submicron structure includes a silica body defining a plurality of pores that are suitable to receive molecules therein, the silica body further defining an outer surface between pore openings of said plurality of pores; and a plurality of anionic molecules attached to the outer surface of the silica body. The anionic molecules provide hydrophilicity to the submicron structure and are suitable to provide repulsion between other similar submicron structures, and the submicron structure has a maximum dimension less than one micron.

Mesoporous silica nanoparticles for biomedical applications

A submicron structure having a silica body defining a plurality of pores is described. The submicron body may be spherical or non-spherical, and may include a cationic polymer or co-polymer on the surface of said silica body. The submicron structure may further include an oligonucleotide and be used to deliver the oligonucleotide to a cell. The submicron structure may further include a therapeutic agent and be used to deliver the therapeutic agent to a cell. An oligonucleotide and therapeutic agent may be used together. For example, when the oligonucleotide is an siRNA, the composition may be used to decrease cellular resistance to the therapeutic agent by decreasing translation of a resistance gene.

Cationic polymer coated mesoporous silica nanoparticles and uses thereof

A submicron structure includes a silica body defining a plurality of pores that are suitable to receive molecules therein, the silica body further defining an outer surface between pore openings of the plurality of pores; and a plurality of anionic molecules attached to the outer surface of the silica body. The anionic molecules provide hydrophilicity to the submicron structure and are suitable to provide repulsion between other similar submicron structures, and the submicron structure has a maximum dimension less than one micron.

A method based is provided for determining the toxicity of engineered nanomaterials (NM). The method comprises in vitro assays for oxidative stress associated with exposure to engineered NM, which comprise assays for: reactive oxygen species production; phase II and glutathione antioxidant molecule expression; activation of MAP and NF-kappa B kinase signaling cascades; production of cytokines, chemokines and adhesion molecules; mitochondrial perturbation and apoptosis; and cellular uptake and subcellular localization of the NM. The method further comprises in vivo assays for oxidative stress in subjects exposed to NM.

Growing community of inventors

Sherman Oaks, CA, United States of America

Andre E Nel