The present invention relates to a cationic lipid having one or more biodegradable groups located in a lipidic moiety (e.g., a hydrophobic chain) of the cationic lipid. These cationic lipids may be incorporated into a lipid particle for delivering an active agent, such as a nucleic acid. The invention also relates to lipid particles comprising a neutral lipid, a lipid capable of reducing aggregation, a cationic lipid of the present invention, and optionally, a sterol. The lipid particle may further include a therapeutic agent such as a nucleic acid.

##STR00001##

The present invention belongs to the field of microbiology, and particularly relates to an application of a Pseudomonas aeruginosa vaccine in prevention and treatment of burn and scald complicated with bacterial infection. The burn and scald of the present invention include burns and scalds, and degree of the scalds includes I degree, superficial II degree, deep II degree, or III degree scalds. Site of the scalds includes skin, mucosa or other tissues. The Pseudomonas aeruginosa vaccine of the present invention can effectively prevent and treat burn and scald complicated with Pseudomonas aeruginosa infection caused by multidrug-resistant Pseudomonas aeruginosa by activating the specific immune response of the body. The Pseudomonas aeruginosa vaccine of the present invention can reduce the bacterial load in the immunized subject through the established immunization procedures, thereby providing a technical solution that can effectively prevent burn and scald complicated with Pseudomonas aeruginosa infection, which avoids the technical problems caused by the use of antibiotics such as poor effectiveness, difficulty in curing and proneness to drug resistance in the prior art to a certain degree.

The present disclosure is generally directed to spherical nucleic acids (SNAs) comprising multiple TLR agonists that enable the simultaneous activation of multiple TLR pathways for maximally synergistic immune activation. In some aspects, the present disclosure provides a spherical nucleic acid (SNA) comprising: (a) a nanoparticle core; (b) one or more toll-like receptor 3 (TLR3) agonists encapsulated in the nanoparticle core; and (c) a shell of oligonucleotides attached to the external surface of the nanoparticle core, the shell of oligonucleotides comprising one or more toll-like receptor 9 (TLR9) agonist oligonucleotides. Methods of using the SNAs are also provided herein.

Embodiments disclosed herein relates to ganglioside GM3-containing mixed lipids nanoparticles having an overall size between 60-100 nm, the making thereof and the uses. The nanoparticles selectively targeted to CD169+ expressing cells such as dendritic cells and macrophage. The nanoparticles are endocytosed by the CD169+ expressing cells.

Provided are a method for preparing liposomes comprising ultrasound reactive microbubbles for drug delivery, comprising (a) a step of producing ultrasound reactive microbubbles comprising an inert gas therein and having a first shell formed on the outer surface thereof, followed by forming a uniform size distribution of the ultrasound reactive microbubbles through an extruder; and (b) a step of producing liposomes comprising the ultrasound reactive microbubbles distributed in a uniform size and a medicament therein and having a second shell formed on the outer surface thereof, followed by forming a uniform size distribution of the liposomes through an extruder; and a liposome using same.

A natural immune agonist complex, consisting of an immune agonist and a targeted liposome, where the immune agonist is M(cGAMP)L.sub.n. The targeted liposome is formed by a nanobody targeting a tumor microenvironment, a cell membrane-targeted penetrating peptide, or a blood-brain barrier-targeted penetrating peptide with a liposome through chemical bonding. This application further provides a preparation and application of the natural immune agonist complex.

The present application is directed to the intravitreal use of spherical nucleic acid (SNA) molecules in the treatment of eye disorders including dry-eye, retinal edema, retinopathy, macular degeneration and glaucoma among others. SNAs have a liposomal core with a plurality of oligonucleotides on the surface forming a shell, wherein the oligonucleotide preferably a TNF-alpha antisense oligonucleotide.

Disclosed are compositions and methods for treating disease or condition caused or exacerbated by S100A9 activity, such as myelodysplastic syndromes (MDS) using a composition comprising an effective amount of a CD33/S100A9 inhibitor.

Methods and compositions are provided for oligonucleotides that bind targets of interest. The targets include cells and microvesicles, such as those derived from various diseases. The oligonucleotides can be used for diagnostic and therapeutic purposes. The target of the oligonucleotides can be a target such as PARP1, HIST1H1B, HIST1H1D, NCL, FBL, SFPQ, RPL12, ACTB, HIST1H4A, SSBP1, NONO, H2AFJ, and DDX21, or a complex, subunit or fragment thereof.

New aminooxylipids of general formula I, wherein n.sub.1=5-30 and X is polymethylene linker of the general formula II where n.sub.2=2-10, or X is polyethylene glycol linker of the general formula III, wherein n.sub.3=1-14 are provided. A method of preparation of the aminooxylipids of general formula I characterized in that the acylation of N-tert-butoxycarbonyl-polymethylenediamine {(CH.sub.3).sub.3C—O—(C═O)—HN—(CH.sub.2).sub.n—NH.sub.2, n=2-13}, or N-tert-butoxycarbonyl-polyethyleglycoldiamine {(CH.sub.3).sub.3C—O—(C═O)—HN—(CH.sub.2).sub.2—[O—(CH.sub.2)].sub.n—O—(CH.sub.2).sub.2NH.sub.2, n=1-14} with in position C(2) symmetrically branched fatty acids of general formula IV, wherein n.sub.1=5-30, in the presence of condensation reagent, or from acid of general formula IV derived acylchloride of general formula V wherein n.sub.1=5-30, produces N-Boc-aminolipids of general formula VI, wherein n.sub.1=5-30 a X is polymethylene linker of the general formula II or X is polyethylene glycol linker of the general formula III.