title: Cell source determines the immunological impact of biomimetic nanoparticles.
abstract: Recently, engineering the surface of nanotherapeutics with biologics to provide them with superior biocompatibility and targeting towards pathological tissues has gained significant popularity. Although the functionalization of drug delivery vectors with cellular materials has been shown to provide synthetic particles with unique biological properties, these approaches may have undesirable immunological repercussions upon systemic administration. Herein, we comparatively analyzed unmodified multistage nanovectors and particles functionalized with murine and human leukocyte cellular membrane, dubbed Leukolike Vectors (LLV), and the immunological effects that may arise in vitro and in vivo. Previously, LLV demonstrated an avoidance of opsonization and phagocytosis, in addition to superior targeting of inflammation and prolonged circulation. In this work, we performed a comprehensive evaluation of the importance of the source of cellular membrane in increasing their systemic tolerance and minimizing an inflammatory response. Time-lapse microscopy revealed LLV developed using a cellular coating derived from a murine (i.e., syngeneic) source resulted in an active avoidance of uptake by macrophage cells. Additionally, LLV composed of a murine membrane were found to have decreased uptake in the liver with no significant effect on hepatic function. As biomimicry continues to develop, this work demonstrates the necessity to consider the source of biological material in the development of future drug delivery carriers.
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Evangelopoulos
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA; Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan 20133, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Parodi
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors.forename: Jonathan O
authors.initials: JO
authors.lastname: Martinez
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors.forename: Iman K
authors.initials: IK
authors.lastname: Yazdi
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA; Department of Molecular Medicine and Medical Biotechnology, University of Naples "Federico II", Via Pansini 5, 80131 Naples, Italy; CEINGE-Biotecnologie Avanzate s.c.a.r.l., Via Gaetano Salvatore 486, 80145 Naples, Italy.
authors.forename: Armando
authors.initials: A
authors.lastname: Cevenini
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors.forename: Anne L
authors.initials: AL
authors.lastname: van de Ven
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Quattrocchi
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA; Escuela de Medicina y Ciencias de la Salud, Tecnologico de Monterrey, Monterrey, Nuevo Leon, Mexico.
authors.forename: Christian
authors.initials: C
authors.lastname: Boada
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors.forename: Nima
authors.initials: N
authors.lastname: Taghipour
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors.forename: Claudia
authors.initials: C
authors.lastname: Corbo
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors.forename: Brandon S
authors.initials: BS
authors.lastname: Brown
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors.forename: Shilpa
authors.initials: S
authors.lastname: Scaria
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors.forename: Xuewu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors.forename: Mauro
authors.initials: M
authors.lastname: Ferrari
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA. Electronic address: etasciotti@tmhs.org.
authors.forename: Ennio
authors.initials: E
authors.lastname: Tasciotti
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000633:toxicity*; D040761:Biomimetic Materials / Q000633:toxicity*; D002478:Cells, Cultured; D007113:Immunity, Innate / Q000276:immunology*; D007962:Leukocytes / Q000187:drug effects* / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D053769:Nanocapsules / Q000633:toxicity*
chemical_list: D001672:Biocompatible Materials; D053769:Nanocapsules
keywords: Biomimicry; Drug delivery; Immunobiology; Leukolike Vector; Multistage nanovector; Nanoparticles