| Nanotechnology has played an important role in cancer therapy in recent years. The nano-drugs can elevate therapeutic efficacy of drugs through longer retention time in the body and specific accumulation at tumor sites via enhanced permeability and retention(EPR) effect. Peptide drugs have attracted increasing attention of researchers because they are readily synthesized, easily degradable in body, and do not cause serious toxic side effects.So, we prepared cytotoxic peptide(KLAKLAK)2(called KLAK) conjugated pHresponsive PEG-poly(β-amino)-esters by 1,4-conjugate addition. The copolymers could self-assemble into micelle-like nanoparticles with pH-responsive property at pH7.4, which were measured by dynamic light scattering(DLS) and transmission electron microscopy(TEM). The endocytosis pathway of P2-KLAK micelles was proved by lysosome colocalization, the mitochondria-regulated apoptosis were proved by JC-1 assay and cytotoxicity of P2-KLAK micelles were proved by CCK-8 assay in MCF-7 cancer cells. The cytotoxicity of P2-KLAK micelles were higher than that of free peptide KLAK, which could be attributed to the efficiently entering into cells by endocytosis pathway and subsequent disruption of mitochondria in cells. Encapsulation of anti-cancer drug DOX into P2-KLAK micelles realized the co-delivery of chemotherapeutic drug and peptide drug and acid-triggered release in cells. The cytotoxicity of DOX-loaded P2-KLAK micelles was higher than that of DOX-loaded P2 micelles and blank P2-KLAK micelles, indicating the enhanced ability to kill MCF-7 cancer cells. Finally, In vivo tumor imaging and growth inhibition was evaluated in MCF-7 cell-xenografted nude mice, demonstrating that DOXloaded P2-KLAK micelles could inhibit tumor growth effectively, which was attributed to the specific accumulation in tumor sites, efficient cellular entry and controlled intracellular release of therapeutic drugs. |
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