The present disclosure is directed, in some embodiments, to methods and compositions of comprising a cell having a non-internalizing receptor, and a nanoparticle surface-modified with a ligand that binds to the non-internalizing receptor.

Engineered nano-liposomes (immuno-nanoliposomes) and their preparation process, for use as a treatment in atherosclerosis therapy, containing therapeutic mono-clonal antibodies and having poly-anions and/or poly-cations on the external surface, to which monoclonal antibodies specific for atheromatous plaques capable of guiding said nano-liposomes are grafted.

In one aspect, the disclosure provides mesoporous silica nanoparticles (MSNPs), monodisperse populations of MSNPs and related protocells which exhibit cell binding specificity. For example, MSNPs and protocells of the disclosure may be used to target specific delivery of therapeutic agents to CD19 or EGFR expressing cancer cells, or target specific delivery of therapeutic agents to other cell types. Related protocells, pharmaceutical compositions and therapeutic and diagnostic methods are also provided.

The disclosure relates generally to polyglutamated antifolates, formulations containing liposomes filled with alpha or D-gamma polyglutamated antifolates, methods of making the polyglutamated antifolates and liposome containing formulations, and methods of using polyglutamated antifolates and liposome containing formulations to treat hyerproliferative disorders (e.g., cancer) and disorders of the immune system (e.g., an autoimmune disease such as rheumatoid arthritis).

Methods for sensitizing tumors and/or cancers in subjects to therapeutic agents are provided. In some embodiments, the methods include administering to the subject one or more compositions that include an effective amount of an inhibitor of TRIM37 activity. Also provided are methods for sensitizing tumors and/or cancers in subjects to therapeutic agents by administering to the subjects one or more compositions that include an effective amount of an inhibitor of TRIM37 activity and purified and isolated antibodies and fragments thereof that have at least one paratope and further have a linker sequence through which the antibody can be conjugated to a carrier in which the linker sequence includes the amino acid sequence ((X).sub.3Cys(X).sub.3, wherein each X is independently any amino acid.

The disclosure relates generally to alpha polyglutamated pralatrexate, formulations containing liposomes filled with alpha polyglutamated pralatrexate, methods of making the alpha polyglutamated pralatrexate and liposome containing formulations, and methods of using polyglutamated alpha polyglutamated pralatrexate and liposome containing formulations to treat hyperproliferative disorders (e.g., cancer) and disorders of the immune system (e.g., an autoimmune disease such as rheumatoid arthritis).

Provided herein is a liposome comprising: a) a conjugate comprising a lysophospholipid and a photosensitizer; b) a first derivatized phospholipid comprising a first phospholipid and a strained cyclooctyne moiety; c) a second derivatized phospholipid comprising a second phospholipid and a polyethylene glycol polymer; and d) a cationic or anionic lipid. Also provided herein is a liposome comprising: a) a conjugate comprising a lysophospholipid and a photosensitizer; b) a first derivatized phospholipid comprising a first phospholipid and a targeting moiety; c) a second derivatized phospholipid comprising a second phospholipid and a polyethylene glycol polymer; and d) a cationic or anionic lipid. The liposomes provided herein can be used, for example, in the treatment of cancer or in the imaging of cancer tumors.

Amyloid precursor protein (APP) dysfunction is a key feature in Alzheimer's disease (AD). The sortilin-related receptor 1 (SORLA) functions as a chaperone protein to APP and has reduced expression in AD brains. The APP and SORLA dysfunction results in homeostasis destabilization. Herpesviruses are suspected to be involved in AD pathogenesis. Using a strategic nucleotide BLAST to query SORL1 and APP nucleotide alignment on all Herpesviridae genomes identified similarity sequences from the Epstein-Barr virus and herpes simplex virus 2. The invention describes a treatment to alleviate EBV and HSV2-mediated neurodegeneration by delivering antisense oligonucleotides sequences that target the EBV and HSV2 non-coding sequences to block SORLA and APP disruption. The invention further describes methods to eradicate EBV infection by delivering inducible expression of antisense oligonucleotides targeting EBV genes or an inducible CRISPR/Cas gene-editing system, together with an expression construct encoding anti-apoptotic proteins or with anti-apoptotic proteins for the prevention of cell-mediated apoptosis.

A method of recovering a population of extracellular vesicles from a biological sample comprising extracellular vesicles and contaminants is described. In one embodiment, the method comprises: a) removing contaminants from the sample, wherein the contaminants are relatively larger or more dense than the extracellular vesicles; b) contacting the sample of step a) with a plurality of binding compositions, each binding composition having first and/or second moieties capable of binding a recognition motif of the target entities under conditions to allow complexing of the extracellular vesicles with the plurality of binding compositions to form a complexed population of extracellular vesicles, the complexed population of extracellular vesicles having an increased volume and/or higher density in comparison to the extracellular vesicles in individual form; and c) recovering the complexed population of extracellular vesicles.

The present disclosure provides target nanodrugs comprising nanocarriers, such as nanodiscs and/or liposomes, encapsulating a therapeutic agent. The nanodrugs may be conjugated to a targeting antibody, such as for delivery of the nanodrug across the blood brain barrier. The nanodrugs may comprise anti-retroviral therapy. Further provided herein are methods for the treatment of a disease or disorder by administering the target nanodrugs, such as for the treatment of HIV.