Compositions and methods for enhancing targeted gene editing and methods of use thereof are disclosed. In the most preferred embodiments, gene editing is carried out utilizing a gene editing composition such as triplex-forming oligonucleotides, CRISPR, zinc finger nucleases, TALENS, or others, in combination with a gene modification potentiating agent such as stem cell factor (SCF), a CHK1 or ATR inhibitor, or a combination thereof. A particular preferred gene editing composition is triplex-forming peptide nucleic acids (PNAs) substituted at the γ position for increased DNA binding affinity. Nanoparticle compositions for intracellular delivery of the gene editing composition are also provided and particular advantageous for use with in vivo applications.

In some aspects, the present disclosure provides vaccine compositions comprising an antigen and a diblock copolymer wherein the diblock copolymer is pH responsive. In some embodiments, these compositions activate the STING and/or the interferon receptor pathways. In some embodiments, the diblock copolymer has a pKa from about 6 to about 7.5. Also provided herein are methods of treatment using these compositions to treat an infectious disease or cancer.

Disclosed are methods useful for the topical therapeutic treatment of skin malignancies including skin cancers and cutaneous metastases using compositions containing nanoparticles of paclitaxel or other taxanes.

Disclosed are methods useful for the topical therapeutic treatment of vulvar intraepithelial neoplasia (VIN) and /or genital warts using compositions containing nanoparticles of paclitaxel or other taxanes.

Hypotonic formulations and methods for delivering drugs to bladder, improving drug absorption and retention therein, and minimizing systemic toxicity, are provided. The formulation includes particles formed from the assembly or association between biocompatible polymers with and without low or high grafting density of polyethylene glycol (PEG) and a wide range of drugs. A hypotonic medium or water allows the particles to penetrate and distribute within bladder tissue, where the particles are capable of dissolution to release drugs for absorption and retention. A reduced level of local and systemic toxicity and side effects of the formulation, compared to delivery of drugs in their free form, provides an effective and safe drug delivery platform for treating bladder or associated diseases or disorders.

The disclosure features novel lipids and compositions involving the same. Nanoparticle compositions include a novel lipid as well as additional lipids such as phospholipids, structural lipids, and PEG lipids. Nanoparticle compositions further including therapeutic and/or prophylactics such as RNA are useful in the delivery of therapeutic and/or prophylactics to mammalian cells or organs to, for example, regulate polypeptide, protein, or gene expression.

The disclosure features novel lipids and compositions involving the same. Nanoparticle compositions include an ionizable lipid, a phospholipid, a first sterol or a tocopherol, and optionally a second sterol different from the first sterol. Nanoparticle compositions further including therapeutic and/or prophylactics such as RNA are useful in the delivery of therapeutic and/or prophylactics to mammalian cells or organs to, for example, regulate polypeptide, protein, or gene expression.

Disclosed are methods useful for the topical therapeutic treatment of skin keratoses including precancerous skin keratoses such as actinic keratosis using compositions containing nanoparticles of paclitaxel or other taxanes.

Compositions and their use are described for delivery of drugs to desired tissues via a light responsive quantum dot (QD) drug delivery system (QD-DDS). The QD-DDS comprises water soluble QD nanoparticles loaded with drug molecules that are releasable from the QD-DDS upon light administration at a wavelength absorbed by the QD.

The invention relates to nanoparticles comprising a solid matrix, wherein the solid matrix comprises albumin and certain xanthophylls, and wherein the xanthophyll is distributed throughout the solid matrix. The present invention also relates to the method for obtaining the nanoparticles and to the products and compositions incorporating them.

The disclosure relates to herpes simplex virus (HSV) ribonucleic acid (RNA) vaccines, as well as methods of using the vaccines and compositions comprising the vaccines. In a preferred embodiment, the vaccine is formulated as a lipid nanoparticle comprising at least one cationic lipid.

The disclosure relates to broad spectrum influenza virus ribonucleic acid (RNA) vaccines, as well as methods of using the vaccines and compositions comprising the vaccine. In a preferred embodiment, the vaccine is formulated as a lipid nanoparticle comprising at least one cationic lipid.

Some aspects of the present disclosure provide nanoparticles comprising a non- cationic liposome with ligands conjugated to its surface and a hydrogel encapsulated in the liposome. In some embodiments, the nanoparticle is used as a delivery system to deliver an agent (e.g., a therapeutic agent or a genome-editing agents) to a cell (e.g., a diseased cell such as a cancer cell). The ligands on the surface of the cationic liposome targets the liposome to cells that express proteins targeted by the ligands on their surface. Methods of treating diseases and disorders, as well as methods of genome-editing are also provided.

Aco-drug is represented by Formula (I) or Formula (II), R-X-NH-CO-CO-OR1 (I) R-X-CO-O-CH2-CO-OR1 (II) where R is a tocol moiety, a tocol analog moiety, or a capsaicinoid moiety; X is a direct bond or a linking group; and OR1 is the residue of an anticancer or antirestenotic agent bearing at least one hydroxyl group by which the CO-OR1 ester linkage is formed. Nanoparticles that include the abovementioned co-drug are also provided, as well as a method of treating a cancer patient that includes administering an effective amount of the co-drug or nanoparticles.

The disclosure relates to respiratory syncytial virus (RSV) ribonucleic acid (RNA) vaccines, as well as methods of using the vaccines and compositions comprising the vaccines.

The invention provides an improved lipid-based nanoparticle, which can be used to deliver a therapeutic agent to a subject, such as but not limited to a mammal, such as but not limited to a human. In certain embodiments, the nanoparticle of the invention has reduced aggregation properties as compared to those taught in the prior art.

Provided are a multispecific antibody targeting the HER2 extracellular domain II and an antigen on an immune effector cell, and a conjugate of the antibody and a nanoparticle, wherein the conjugate can further comprise a binding portion specifically binding to the HER2 extracellular domain IV. Also provided are a pharmaceutical composition comprising the multispecific antibody or the conjugate thereof, and the use of the multispecific antibody or the conjugate thereof in the preparation of a drug for treating HER2-positive tumours.

Compositions and methods are described for delivery of drugs to desired tissues via soluble quantum dots.

The disclosure provides pharmaceutical compositions and method of using the compositions, wherein the compositions comprise liposomes that contain two or more anticancer drugs. In various embodiments the components of the liposomes can include a) a phospholipid, b) a pegylated lipid, c) an aqueous core, and d) at least one covalently-linked drug-conjugated lipid, an encapsulated drug, or a combination thereof, wherein the drug of the lipid-drug conjugate, encapsulated drug, or both, are anticancer drugs.

The method for the production of these nanoparticles and the applications thereof in imaging and in therapy also form part of the invention.

The invention generally relates to compositions and methods for transporting substances across mucosal barriers. The invention also relates to methods of making and using such substances.

The present disclosure relates to an antimicrobial peptide conjugated with nanoparticles, in particular the antimicrobial peptide LL37-conjugated gold nanoparticles for use in medicine or cosmetic, for human or animals, namely in the treatment of wound healing or in the treatment of ischemic or vascular diseases, comprising a gold nanoparticle and a plurality of LL-37 peptides, wherein the plurality of LL-37 peptides is bound to the gold nanoparticle surface.

The nanoparticles of the present invention consist of a molecular aggregate containing an amphipathic block polymer that has a hydrophilic block and a hydrophobic block. It is preferable that the amphipathic block polymer be biodegradable. The nanoparticles of the present invention are obtained by granulating into particles an amphipathic block polymer in the presence of an amino acid whose isoelectric point is 7 or less. In one embodiment, the granulation is done by bringing a solution containing an amphipathic block polymer or the dried product thereof into contact with an aqueous liquid. Granulation can be done in the presence of an amino acid by including an amino acid whose isoelectric point is 7 or less in either a solution that contains an amphipathic block polymer or in an aqueous liquid, or in both.

A multi-component nanoconstruct for use in diagnostic and therapeutic applications includes at least three nanoparticles linked together to form the nanochain. The nanoparticles are linked to form the nanochain by linking first linkers and/or second linkers disposed on separate nanoparticles.

Resumen de: US2018264130A1

The present invention features methods of directly targeting specific cell surface receptors on the M2 macrophage for antibody or nanoparticle directed therapy.