The disclosure relates to nanoparticle drug conjugates (NDC) that comprise ultrasmall nanoparticles, folate receptor (FR) targeting ligands, and linker-drug conjugates, and methods of making and using them to treat cancer.

Peptides and Peptide-lipid conjugates are provided in which the peptide has the general Formula (I)

##STR00001## wherein, A.sup.1 is selected from serine, threonine, O—C.sub.1-6 alkyl serine, and O—C.sub.1-6 alkyl threonine; A.sup.2 is selected from serine, threonine, O—C.sub.1-6 alkyl serine, and O—C.sub.1-6 alkyl threonine; A.sup.3 is selected from glutamic acid, glutamine, asparagine, and aspartic acid; A.sup.4 is proline; each A.sup.5 is independently selected from a natural or modified amino acid;
The peptide-lipid conjugates can be used in lipid formulations for the delivery of nucleic acids.

Disclosed are peptides and peptidomimetics that in some embodiments include the amino acid sequence KRGARST or (SEQ ID NO: 1), AKRGARSTA or (SEQ ID NO: 2), or CKRGARSTC (SEQ ID NO: 3). Also disclosed are conjugates and compositions that include the peptides and/or peptidomimetics, methods for directing a moiety to tumor lymphatic vasculature, methods for imaging tumor lymphatic vasculature, methods for reducing or inhibiting tumor metastasis, methods for reducing the number of tumor lymphatic vessels, methods for treating cancer, methods for treating a disease or disorder associated with a gC1q/p32 receptor biological activity, methods for detecting the presence of a gC1q/p32 receptor, methods for detecting interactions between gC1q/p32 receptors and the presently disclosed conjugates and compositions, methods for delivering the presently disclosed conjugates and compositions to gC1q/p32 receptors, methods for assessing gC1q/p32 receptor levels in cells, methods for identifying subjects having diseases associated with gC1q/p32 receptor biological activities, and methods for screening for compounds that interact with gC1q/p32 receptors.

The description provides a molecular switch comprising at least two nanoparticles, wherein a first nanoparticle comprises DNA and/or RNA oligonucleotides, and a second nanoparticle which is complementary to the first nanoparticle comprises reverse complementary DNA and/or RNA oligonucleotides of the first nanoparticle; wherein the complementary nanoparticles interact under physiological conditions leading to thermodynamically driven conformational changes in the first and second nanoparticles leading to their re-association to release one or more duplexes comprising said DNA and/or RNA oligonucleotides and the reverse complementary DNA and/or RNA oligonucleotides, and wherein the nanoparticles are not rings and have no single stranded toeholds.

Provided are targeted nanoparticles. In certain embodiments, the targeted nanoparticles comprise a nanoparticle and a myeloid cell (MC) targeting moiety stably associated with the outer surface of the nanoparticle. According to some embodiments, the MC targeting moiety is an immunosuppressive myeloid cell (isMC) targeting moiety. In certain embodiments, the targeted nanoparticles further comprise a detectable label (e.g., an in vivo imaging agent), a drug, or both. Also provided are compositions comprising the targeted nanoparticles of the present disclosure. Methods of using the targeted nanoparticles to image MCs (e.g., isMCs) and/or to modulate and/or disrupt MCs (e.g., isMCs) are also provided.

Disclosed herein are compositions and methods for targeted treatment of liver cancers with Paclitaxel and miR-122. The disclosed composition comprises RNA nanostructure conjugated to a hepatocyte targeting ligand, paclitaxel, and miR-122 for use in intracellular drug delivery to liver cancer cells. The RNA nanoparticle can involve three or more self-assembled synthetic RNA oligonucleotides that form a central core domain and at least three double-stranded arms arranged around the core domain and extending away from the central core domain.

A lipid composition containing a nucleic acid, wherein the lipid composition comprises a peptide-lipid conjugate, is provided. The peptide of the peptide-lipid conjugates can be from 4 to 52 amino acids in length. Methods of using the lipid composition in the in vivo delivery of nucleic acids are further provided.

Disclosed are visible light-activatable antitumor self-assembled nanoparticles or antitumor immunity-inducing self-assembled nanoparticles. The self-assembled nanoparticles induce potent apoptosis in cancer cells and increase their own anticancer immunogenicity, thereby maximizing their therapeutic efficacy for cancer.

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.

Described herein are methods, formulations and kits for treating a patient with triple-negative breast cancer with nanoparticle complexes comprising a carrier protein (e.g., albumin), paclitaxel and a binding agent specific for a target antigen expressed by the cells (e.g., an anti-VEGF antibody).