The disclosure provides methods and compositions for delivering RNA constructs to cells for functional expression and/or activity. In some aspects, the disclosure provides a composition comprising a multi-functionalized nanoparticle. The multi-functionalized nanoparticles comprise a core functionalized with at least one RNA molecule, at least one cell penetrating peptide (CPP), and at least one positively charged moiety, each of which is independently attached to the core, optionally with linker moieties. In some embodiments, the RNA molecule is an uncapped mRNA molecule with the 5′ end attached to a linker moiety that is attached to the core. The multi-functionalized nanoparticle is substantially neutral, negatively or positively charged. The multi-functionalized nanoparticle can be used in methods of delivering and causing the expression of polypeptides of interest in a cell for various purposes, including vaccination, cancer treatment, extension of telomeres, modification of cellular signaling pathways, and the like.

The disclosure provides methods and compositions for delivering RNA constructs to cells for functional expression and/or activity. In some aspects, the disclosure provides a composition comprising a multi-functionalized nanoparticle. The multi-functionalized nanoparticles comprise a core functionalized with at least one RNA molecule, at least one cell penetrating peptide (CPP), and at least one positively charged moiety, each of which is independently attached to the core, optionally with linker moieties. In some embodiments, the RNA molecule is an uncapped mRNA molecule with the 5′ end attached to a linker moiety that is attached to the core. The multi-functionalized nanoparticle is substantially neutral, negatively or positively charged. The multi-functionalized nanoparticle can be used in methods of delivering and causing the expression of polypeptides of interest in a cell for various purposes, including vaccination, cancer treatment, extension of telomeres, modification of cellular signaling pathways, and the like.

A microporous gel system for certain applications, including biomedical applications, includes an aqueous solution containing plurality of microgel particles including a biodegradable crosslinker. In some aspects, the microgel particles act as gel building blocks that anneal to one another to form a covalently-stabilized scaffold of microgel particles having interstitial spaces therein. In certain aspects, annealing of the microgel particles occurs after exposure to an annealing agent that is endogenously present or exogenously added. In some embodiments, annealing of the microgel particles requires the presence of an initiator such as exposure to light. In particular embodiments, the chemical and physical properties of the gel building blocks can be controlled to allow downstream control of the resulting assembled scaffold. In one or more embodiments, cells are able to quickly infiltrate the interstitial spaces of the assembled scaffold.

A microporous gel system for certain applications, including biomedical applications, includes an aqueous solution containing plurality of microgel particles including a biodegradable crosslinker. In some aspects, the microgel particles act as gel building blocks that anneal to one another to form a covalently-stabilized scaffold of microgel particles having interstitial spaces therein. In certain aspects, annealing of the microgel particles occurs after exposure to an annealing agent that is endogenously present or exogenously added. In some embodiments, annealing of the microgel particles requires the presence of an initiator such as exposure to light. In particular embodiments, the chemical and physical properties of the gel building blocks can be controlled to allow downstream control of the resulting assembled scaffold. In one or more embodiments, cells are able to quickly infiltrate the interstitial spaces of the assembled scaffold.

Provided in the present invention are highly stable D-configuration polypeptides DVAP and SVAP having a high binding activity to the GRP78 protein, and also provided are an L-configuration polypeptide LVAP and a DVAP-or SVAP-modified model drug and a macromolecule carrier material, and the use thereof in the construction of a tumour image and a drug-delivery system for targeted treatment.

Disclosed herein are compositions and methods for treating a subject having cancer and other ferroptosis disorders with high density lipoprotein-like nanoparticles that induce ferroptosis.

A novel nucleic acid delivery system is provided containing a linear histidine-lysine rich cysteine-containing peptide bearing a targeting function, and a four branched histidine-lysine rich polypeptide. The delivery system includes a nucleic acid, such as an siRNA. The components form a nanoparticle complex through multiple non-covalent interactions between the phosphates of siRNA and histidine/lysine of the polypeptide, with reduced toxicity. The stable complex selectively delivers the genetic material to cells. The targeting function enhances the efficiency of the nucleic acid delivery and transfection.

Carrier molecules also are provided that have the ability to deliver a therapeutic molecule to a specific cell within a tissue in the body. The carrier molecule is modified with a targeting ligand capable of binding to specific receptors present or upregulated on the cell to be targeted. The therapeutic molecule is an siRNA, miRNA, or other oligonucleotide. The targeting moiety is a small molecule, peptide, or protein that shows an affinity for a receptor present on the cell to be targeted.

The present disclosure provides compositions comprising protein encapsulated nanoparticles, and methods of making said compositions. In an aspect, a composition may comprise a drug delivery vector and a therapeutic substance, wherein the composition elutes at least 1.0 pg of the therapeutic substance per 100,000 particles of the drug delivery vector over a period of time under conditions of a drug delivery vector release buffer, wherein the therapeutic substance, drug delivery vector and drug delivery vector release buffer comprise a solution, wherein the solution is centrifuged and a portion stored at about 1 to 10° C., and wherein the elution of the therapeutic substance is determined by ELISA assay. This disclosure further describes a method of controlling an immunophenotype in a patient suffering from a disease which impacts the immune system.

The present disclosure provides compositions comprising protein encapsulated nanoparticles, and methods of making said compositions. In an aspect, a composition may comprise a drug delivery vector and a therapeutic substance, wherein the composition elutes at least 1.0 pg of the therapeutic substance per 100,000 particles of the drug delivery vector over a period of time under conditions of a drug delivery vector release buffer, wherein the therapeutic substance, drug delivery vector and drug delivery vector release buffer comprise a solution, wherein the solution is centrifuged and a portion stored at about 1 to 10° C., and wherein the elution of the therapeutic substance is determined by ELISA assay. This disclosure further describes a method of controlling an immunophenotype in a patient suffering from a disease which impacts the immune system.

The present invention provides a compound of Formula (I) as defined herein. The present invention also provides a nanoparticle comprising a plurality of the conjugates of the present invention, and methods of using the nanoparticles for drug delivery, treating a disease, and methods of imaging.