title: Doxorubicin-triggered self-assembly of native amphiphilic peptides into spherical nanoparticles.
abstract: In this study, we designed and fabricated self-assembly nanospheres, which consisted of a P45 peptide and doxorubicin (Dox). P45 is a hybrid peptide composed of an Arg-Gly-Asp motif linked to the human matrilin-1 C-terminal domain by a serine linker. The fabricated nanospheres had a uniform mulberry-like spherical shape, a diameter of 63 nm, excellent polydispersity, and high Dox drug-loading efficiency. In the presence of the RGD motif, the Dox/P45 nanospheres could specifically target A549 cells, which have high integrin αvβ3 expression. Confocal laser scanning microscopy and flow cytometry results showed the enhanced cellular uptake of Dox/P45, and the CCK8 assay indicated the low cytotoxicity of the nanospheres to normal human embryonic kidney 293 cells. Furthermore, the fabricated nanospheres were stable in a physiological environment, but they disassembled and exhibited a rapid Dox release in an acidic atmosphere, allowing for a specific pH-sensitive release into cytosol after cellular uptake. These results suggest that natural amphiphilic peptides can be used as carriers of nanodrugs for targeting delivery as well as controlled drug release for cancer therapy.
authors.affiliation: Center of Clinical Laboratory Medicine of Zhongda Hospital, Southeast University, Nanjing, 210009, China.|Medical School, Southeast University, Nanjing, 210009, China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Fan
authors.affiliation: Medical School, Southeast University, Nanjing, 210009, China.
authors.forename: Fengfeng
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Medical School, Southeast University, Nanjing, 210009, China.
authors.forename: Xiyong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Center of Clinical Laboratory Medicine of Zhongda Hospital, Southeast University, Nanjing, 210009, China.|Medical School, Southeast University, Nanjing, 210009, China.
authors.forename: Guoqiu
authors.initials: G
authors.lastname: Wu
mesh_terms: D000072283:A549 Cells; D020816:Amino Acid Motifs; D002942:Circular Dichroism; D003600:Cytosol / Q000378:metabolism; D003692:Delayed-Action Preparations; D004317:Doxorubicin / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D005434:Flow Cytometry; D057809:HEK293 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D061986:MCF-7 Cells; D008823:Micelles; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy; D009842:Oligopeptides / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008823:Micelles; D009842:Oligopeptides; D010455:Peptides; D011108:Polymers; C047981:arginyl-glycyl-aspartic acid; D004317:Doxorubicin
keywords: cancer therapy; drug delivery; matrilin-1 C-terminal peptide; nanosphere; self-assembly