Nanoparticle and use thereof for the combinatorial therapy of endoplasmic reticulum stress inducer and immunotherapeutic to tumors and immune cells
AssigneeNational Yang Ming Chiao Tung University
InventorYu-Li Lo
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Abstract
Multifunctional nanoparticles incorporate an ERS inducer (p97 inhibitors) and immunotherapeutics (immune-modulating miR or aptamer plus immunoadjuvants) to address the poor aqueous solubility and toxicity associated with p97 inhibitors and immunotherapeutics while also enhancing the immune activation of these therapeutics. The nanoformulation offers several advantages, such as pH-sensitivity, self-detachable coating, active targeting, and intracellular localization in tumors, and has the potential to overcome the limitations of systemic administration, such as the degradation of nucleic acid therapeutics and toxicities associated with ERS inducer.
Claims21
A target nanoparticle, comprising:
- a nanoparticle core, wherein the surface of the nanoparticle core is modified with a target molecule;
- a therapeutic agent inside the nanoparticle core;
- and
- an outer shell layer surrounding the outside surface of the nanoparticle core, the outer shell layer is coated with a tumor microenvironment acid-detachable polymer;
- wherein the target molecule of the surface of the nanoparticle core and the tumor microenvironment acid-detachable polymer on the outer layer form a space and charge barrier via the electrostatic interaction;
- wherein the target molecule comprises a cation target peptide and/or an anion target aptamer;
- wherein the cation target peptide comprises a tumor target peptide, an immune cell target peptide, an endoplasmic reticulum target peptide or a combination thereof;
- wherein the anion target aptamer comprises a tumor target aptamer, an immune cell target aptamer or a combination thereof;
- wherein the therapeutic agent comprises an ERS inducer and a nucleic acid immunomodulator;
- wherein the tumor target peptide of the target molecule comprises C peptide (SEQ ID NO 2).
Dependencies are inferred from the claim text.