Abstract: In various embodiments drug delivery vehicles and uses thereof are provided. In certain embodiments the drug delivery vehicles comprise: 1) a silicasome comprising a mesoporous silica nanoparticle coated with a lipid bilayer and further comprising a CXCR4 antagonist; or 2) a liposome comprising a lipid bilayer comprising where said liposome further comprises a CXCR4 antagonist. In certain embodiments the CXCR4 antagonists are selected from the group consisting of AMD3100, AMD3465, and AMD070.

Abstract: In various embodiments tolerogenic nanoparticles are provided that induce immune tolerance to one or more desired antigen(s) and/or that reduce an immune response to those antigen(s). In certain embodiments the tolerogenic nanoparticle comprises a nanoparticle comprising a biocompatible polymer; an antigen disposed within or attached to said biocompatible polymer where said antigen comprises an antigen to which immune tolerance is to be induced by administration of said tolerogenic nanoparticle to a mammal; and a first targeting moiety that binds to a scavenger receptor in the liver, and/or a second targeting moiety that binds to a mannose receptor in the liver, and/or a third targeting moiety that binds to hepatocytes, wherein said first and/or second and/or third targeting moiety are attached to the surface of said nanoparticle.

Abstract: 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.

Abstract: In various embodiments tolerogenic nanoparticles are provided that induce immune tolerance to one or more desired antigen(s) and/or that reduce an immune response to those antigen(s). In certain embodiments the tolerogenic nanoparticle comprises a nanoparticle comprising a biocompatible polymer, a cationic lipid, or a combination thereof; an antigen disposed within or attached to said biocompatible polymer or a nucleic acid encoding said antigen, where said antigen comprises an antigen to which immune tolerance is to be induced by administration of said tolerogenic nanoparticle to a mammal; and a targeting moiety that binds to a scavenger receptor in the liver.

Abstract: 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.

Abstract: 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).

Abstract: In various embodiments immunogenic nanoparticles are provided that are capable of raising an immune response directed against SARS-CoV-2. In certain embodiments the immunogenic nanoparticles comprise mRNA multi-epitope vaccines that can be used in combination with or independent of other covid-19 vaccines (e.g., the spike protein mRNA vaccine(s)) to invoke a strong CD8+ or CD4+ T-cell as well as neutralizing antibody producing B-cell responses. In certain embodiments this vaccine is based on the rational combination of well-conserved T- and B-cell epitopes identified COVID-19 and viral variants.

Abstract: In various embodiments, drug delivery vehicles are provided for co-delivery of a chemotherapeutic agent and a TLR7/8 agonist and/or a lipoxin to a cancer. In certain embodiments the vehicles comprise a silicasome comprising: a porous nanoparticle encapsulated in a lipid bilayer, where the lipid bilayer contains a lipoxin and/or a lipid compatible TLR7/8 agonist disposed in the lipid bilayer, and the chemotherapeutic agent is contained in pores comprising the porous nanoparticle and the chemotherapeutic agent comprises a chemotherapeutic agent that induces immunogenic cell death (ICD); or a liposome comprising a lipid bilayer where the lipid bilayer contains a lipoxin and/or a lipid compatible a TLR7/8 agonist disposed in the lipid bilayer; and the chemotherapeutic agent is inside the liposome and the chemotherapeutic agent comprises a chemotherapeutic agent that induces immunogenic cell death (ICD).

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: In various embodiments, drug delivery vehicles that contain one or more metal-based therapeutic agents are provided. In certain embodiments, the drug delivery vehicle comprises: a silica nanoparticle comprising one or more cavities disposed within the nanoparticle and an outside surface where the one or more cavities are in fluid communication with the outside surface of the nanoparticle; a metal-based (e.g., platinum-based) chemotherapeutic drug disposed on the surface of the nanoparticle and/or within the one or more cavities of the nanoparticle where the drug comprises a cationic, metal-based drug; and a lipid bilayer disposed on the surface of the nanoparticle where the lipid bilayer fully encapsulates and seals the nanoparticle.

Abstract: In various embodiments, methods of treating a cancer are provided. In certain embodiments, the methods comprise administering to a mammal in need thereof i) one or more checkpoint inhibitor(s); and ii) one or more camptothecin analogs, and, optionally, or one or more autophagy inhibitors wherein said camptothecin analog, and one or more autophagy inhibitors, when present, are provided inside a delivery vehicle where said delivery vehicle comprises: a nanoparticle comprising one or more cavities disposed within said nanoparticle and an outside surface where said one or more cavities are in fluid communication the outside surface of said nanoparticle; said one or more camptothecin analog, one or more autophagy inhibitors, when present, are disposed within said one or more cavities; and a lipid bilayer is disposed on the surface of said nanoparticle where said lipid bilayer fully encapsulates the nanoparticle.

Abstract: In various embodiments nanoparticle drug delivery vehicles are provided herein for the effective delivery of a GSK3 inhibitor. In certain embodiments the drug delivery vehicle comprises a nanoparticle comprising one or more cavities disposed within the nanoparticle and an outside surface where the one or more cavities are in fluid communication the outside surface of the nanoparticle; a GSK3 inhibitor disposed within said one or more cavities; and a lipid bilayer disposed on the surface of said nanoparticle where said lipid bilayer fully encapsulates said nanoparticle.

Abstract: 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.

Abstract: In various embodiments immunogenic nanoparticles are provided that are capable of raising an immune response directed against one or more viral proteins and/or protein fragments. In certain embodiments the immunogenic nanoparticles raise an immune response directed against a virus (e.g., SARS-CoV-2 (2019-nCoV), SARS-CoV-2, and MERS-CoV, and the like). In certain embodiments the immunogenic nanoparticles comprise a nanoparticle formed from one or more biocompatible polymer(s), one or more viral proteins or fragments thereof encapsulated within or attached to the biocompatible polymer(s) where the viral protein or fragment thereof comprises an antigen to which an immune response is to be induced by administration of the immunogenic nanoparticle to a mammal and where the immunogenic nanoparticle further comprises an adjuvant (e.g., a STING agonist).

Abstract: In various embodiments tolerogenic nanoparticles are provided that induce immune tolerance to one or more desired antigen(s) and/or that reduce an immune response to those antigen(s). In certain embodiments the tolerogenic nanoparticle comprises a nanoparticle comprising a biocompatible polymer; an antigen disposed within or attached to said biocompatible polymer where said antigen comprises an antigen to which immune tolerance is to be induced by administration of said tolerogenic nanoparticle to a mammal; and a first targeting moiety that binds to a scavenger receptor in the liver, and/or a second targeting moiety that binds to a mannose receptor in the liver, and/or a third targeting moiety that binds to hepatocytes, wherein said first and/or second and/or third targeting moiety are attached to the surface of said nanoparticle.

Abstract: 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.

Abstract: 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.