title: Immune Cell-Mediated Biodegradable Theranostic Nanoparticles for Melanoma Targeting and Drug Delivery.
abstract: Although tremendous efforts have been made on targeted drug delivery systems, current therapy outcomes still suffer from low circulating time and limited targeting efficiency. The integration of cell-mediated drug delivery and theranostic nanomedicine can potentially improve cancer management in both therapeutic and diagnostic applications. By taking advantage of innate immune cell's ability to target tumor cells, the authors develop a novel drug delivery system by using macrophages as both nanoparticle (NP) carriers and navigators to achieve cancer-specific drug delivery. Theranostic NPs are fabricated from a unique polymer, biodegradable photoluminescent poly (lactic acid) (BPLP-PLA), which possesses strong fluorescence, biodegradability, and cytocompatibility. In order to minimize the toxicity of cancer drugs to immune cells and other healthy cells, an anti-BRAF V600E mutant melanoma specific drug (PLX4032) is loaded into BPLP-PLA nanoparticles. Muramyl tripeptide is also conjugated onto the nanoparticles to improve the nanoparticle loading efficiency. The resulting nanoparticles are internalized within macrophages, which are tracked via the intrinsic fluorescence of BPLP-PLA. Macrophages carrying nanoparticles deliver drugs to melanoma cells via cell-cell binding. Pharmacological studies also indicate that the PLX4032 loaded nanoparticles effectively kill melanoma cells. The "self-powered" immune cell-mediated drug delivery system demonstrates a potentially significant advancement in targeted theranostic cancer nanotechnologies.
authors.affiliation: Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, 16802, USA.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, 16802, USA.
authors.forename: Yixue
authors.initials: Y
authors.lastname: Su
authors.affiliation: Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, 16802, USA.
authors.forename: Gloria B
authors.initials: GB
authors.lastname: Kim
authors.affiliation: Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, 16802, USA.
authors.forename: Erhan
authors.initials: E
authors.lastname: Selvi
authors.affiliation: Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, 16802, USA.
authors.forename: Chuying
authors.initials: C
authors.lastname: Ma
authors.affiliation: Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, 16802, USA.
authors.forename: Virginia
authors.initials: V
authors.lastname: Aragon-Sanabria
authors.affiliation: Department of Urology, The University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
authors.forename: Jer-Tsong
authors.initials: JT
authors.lastname: Hsieh
authors.affiliation: Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, 16802, USA.
authors.forename: Cheng
authors.initials: C
authors.lastname: Dong
authors.affiliation: Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, 16802, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
mesh_terms: D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D000068936:Theranostic Nanomedicine / Q000379:methods*
chemical_list: D004337:Drug Carriers; D011108:Polymers
keywords: drug delivery; immune cells; melanoma; nanoparticles; theranostics