Purpose Design and synthesis of a tumor responsive nanoparticlebased\nsystem for imaging and treatment of various cancers.\nMethods Manganese oxide nanoparticles (Mn3O4 NPs) were synthesized\nand modified with LHRH targeting peptide or antimelanoma\nantibodies (cancer targeting moieties) and a MMP2 cleavable\npeptide (a possible chemotactic factor). Nanostructured lipid\ncarriers (NLCs) were used to entrap the BRAF inhibitor,\nvemurafenib, and enhance cytotoxicity of the drug. Size distribution,\nstability, drug entrapment, cytotoxicity and genotoxicity of synthesized\nnanoparticles were studied in vitro. Enhancement of MRI signal by\nnanoparticles and their body distribution were examined in vivo on\nmouse models of melanoma, ovarian and lung cancers.\nResults Uniform, stable cancer-targeted nanoparticles\n(PEGylated water-soluble Mn3O4 NPs and NLCs) were synthesized.\nNo signs of cyto-,genotoxicity and DNA damage were\ndetected for nanoparticles that do not contain an anticancer drug.\nEntrapment of vemurafenib into nanoparticles significantly enhanced\ndrug toxicity in cancer cells with targeted V600E mutation.\nThe developed nanoparticles containing LHRH and MMP2 peptides\nshowed preferential accumulation in primary and metastatic\ntumors increasing theMRI signal in mice with melanoma, lung and\novarian cancers.\nConclusions The proposed nanoparticle-based systems provide\nthe foundation for building an integrated MRI diagnostic and\ntherapeutic approach for various types of cancer.
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