Tumor pH-shiftable coating and the nucleus-directed nanoparticles facilitate the targeted chemotherapy and gene therapy against multiple cancers and use thereof

pH-shiftable nanoparticles, comprising:

• solid lipid nanoparticles (SLN) and liposomes (LIP),
• a surface of a nanoparticle core of the SLN and of the LIP, wherein the surface of the nanoparticle core of the SLN and the LIP is modified with a cationic target molecule,
• a therapeutic agent inside the nanoparticle core of the SLN and the LIP;
• and
• an outer layer surrounding the outside surface of the nanoparticle core of the SLN and of the LIP, the outer layer is coated with an acid-detachable polymer, wherein the acid-detachable polymer is pH sensitive and responds to acidic pH;
• wherein the cationic target molecule on the surface of the nanoparticle core of the SLN and of the LIP and the acid-detachable polymer on the outer layer form a space and charge barrier via electrostatic interaction,
• wherein the cationic target molecule of the SLN is a bifunctional peptide, wherein the bifunctional peptide possesses features of a tumor-homing moiety and cell-penetrating properties, wherein the bifunctional peptide is T peptide SEQ ID NO:
• 3,
• wherein the cationic target molecules of the LIP are the bifunctional peptide and a cell nucleus-targeted peptide, wherein the bifunctional peptide is T peptide SEQ ID NO:
• 3, and wherein the cell nucleus-targeted peptide is R peptide SEQ ID NO:
• 4.