Abstract: At present, there is a great need for the development of new tumor pH-shiftable nanoparticles that are effective to reduce side effects, enhance active tumor focusing, improve the cellular uptake, and nuclear/cytoplasmic targeting of chemotherapy and gene therapeutic. Hence, we designed novel solid lipid nanoparticles (SLN) and liposomes (Lip) to deliver microRNA and antineoplastic agent, respectively. The designed SLN and liposomes incorporating microRNA and anticancer drugs in the core, which is surrounded by lipids modified with peptide T (a ligand plus a cell-penetrating peptide) and a nucleus-targeted sequence of peptide R as the inner shell. Moreover, coating a pH-responsive polymer (PGA-PEG) on the outer layer of Lip-TR (PGA-Lip-TR) and SLN-T (PGA-SLN-T) can protect the peptide T and R from degradation by peptidases during systemic circulation and enhance directing to the acidic tumor sites.

Abstract: Currently, the present invention provides a pH-sensitive lipid nanoparticle, comprising: a nanoparticle core composed of a mixture of lipid and/or surfactant, and the surface of the nanoparticle core comprising: a imine-omPEG, the imine is a pH-sensitive linker; and a PEG-peptide, wherein the peptide is selected from the group consisting of a RF peptide, a K peptide, and a H peptide; wherein the RF peptide is a potent CPP, the K peptide is a mitochondria-targeting peptide and the H peptide is a cancer specific binding peptide; a lipid, inside the nanoparticle core; wherein the lipid nanoparticle encapsulating a targeting agent.

Abstract: At present, there is a great need for the development of new tumor pH-shiftable nanoparticles that are effective to reduce side effects, enhance active tumor focusing, improve the cellular uptake, and nuclear/cytoplasmic targeting of chemotherapy and gene therapeutic. Hence, we designed novel solid lipid nanoparticles (SLN) and liposomes (Lip) to deliver microRNA and antineoplastic agent, respectively. The designed SLN and liposomes incorporating microRNA and anticancer drugs in the core, which is surrounded by lipids modified with peptide T (a ligand plus a cell-penetrating peptide) and a nucleus-targeted sequence of peptide R as the inner shell. Moreover, coating a pH-responsive polymer (PGA-PEG) on the outer layer of Lip-TR (PGA-Lip-TR) and SLN-T (PGA-SLN-T) can protect the peptide T and R from degradation by peptidases during systemic circulation and enhance directing to the acidic tumor sites.

Abstract: Currently, the present invention provides a pH-sensitive lipid nanoparticle, comprising: a nanoparticle core composed of a mixture of lipid and/or surfactant, and the surface of the nanoparticle core comprising: a imine-omPEG, the imine is a pH-sensitive linker; and a PEG-peptide, wherein the peptide is selected from the group consisting of a RF peptide, a K peptide, and a H peptide; wherein the RF peptide is a potent CPP, the K peptide is a mitochondria-targeting peptide and the H peptide is a cancer specific binding peptide; a lipid, inside the nanoparticle core; wherein the lipid nanoparticle encapsulating a targeting agent.