Dataset Information

Optimization of critical parameters for coating of polymeric nanoparticles with plasma membrane vesicles by sonication.

ABSTRACT: Top-down functionalization of nanoparticles with cellular membranes imparts nanoparticles with enhanced bio-interfacing capabilities. Initial methods for membrane coating involved physical co-extrusion of nanoparticles and membrane vesicles through a porous membrane; however, recent works employ sonication as the disruptive force to reform membranes around the surface of nanoparticles. Although sonication is widely used, there remains a paucity of information on the effects of sonication variables on coating efficiency, leading to inconsistent membrane coating across studies. In this work, we present a systematic analysis of the sonication parameters that influence the membrane coating. The results showed that sonication amplitude, time, temperature, membrane ratio, sample volume, and density need to be considered in order to optimize membrane coating of polymeric nanoparticles.

SUBMITTER: Yang F

PROVIDER: S-EPMC8671476 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Optimization of critical parameters for coating of polymeric nanoparticles with plasma membrane vesicles by sonication.

Yang Feipeng F Cabe Maleen H MH Ogle Sean D SD Sanchez Veronica V Langert Kelly A KA

Scientific reports 20211214 1

Top-down functionalization of nanoparticles with cellular membranes imparts nanoparticles with enhanced bio-interfacing capabilities. Initial methods for membrane coating involved physical co-extrusion of nanoparticles and membrane vesicles through a porous membrane; however, recent works employ sonication as the disruptive force to reform membranes around the surface of nanoparticles. Although sonication is widely used, there remains a paucity of information on the effects of sonication variabl ...[more]

PMID: 34907240

Similar Datasets

Project description:BackgroundA number of immunotherapeutic approaches have been developed and are entering the clinic. Bispecific antibodies (BsAbs) are one of these modalities and induce robust efficacy by endogenous T cells in several hematological malignancies. However, most of the treated patients experience only a temporary benefit. Currently available BsAbs provide only anti-CD3 antibody-mediated T-cell stimulation, but not the costimulation or cytokine signaling essential for full T-cell activation. Here, we hypothesized that the simultaneous input of more comprehensive signals would elicit more robust and durable effector T-cell functions.MethodsWe genetically engineered the leukemia cell line K562 to express BsAbs, costimulatory ligands, cytokines, and blocking antibodies against immune checkpoint molecules on the cell surface, from which we obtained plasma membrane fractions by mechanical homogenization and subsequent isolation steps. Plasma membranes were reconstituted on the poly (lactic-co-glycolic acid) surface to generate membrane-coated nanoparticles (NPs). Alternatively, nano-sized membrane vesicles (MVs) were generated by ultrasonic dispersion of the isolated membranes. The antitumor function of NPs and MVs loaded with various immunomodulatory factors was evaluated in vitro and in vivo.ResultsBoth membrane-coated NPs and MVs induced BsAb-mediated antigen-specific cytotoxic activity in non-specific T cells, with MVs inducing a slightly better response in vivo. Importantly, T-cell activation was elicited only in the presence of target tumor cells, providing a safety advantage for clinical use. NPs and MVs expressing costimulatory molecules (CD80/4-1BBL) and cytokines (interleukin (IL)-7/IL-15) further enhanced effector T-cell function and induced therapeutic efficacy in vivo. In addition, MVs expressing immune checkpoint antibodies and inflammatory cytokines IL-12 and IL-18 induced objective antitumor responses in solid tumor models partly by converting immunosuppressive macrophages to proinflammatory phenotypes and inducing cytotoxic T-cell infiltration into the tumor. Finally, we showed that MVs were also engineered to activate natural killer (NK) cells by loading multiple ligands. MVs loaded with BsAbs, 4-1BBL, IL-15, and IL-21 induced NK-cell cytotoxic activity in an antigen-specific manner.ConclusionsWe developed antitumor NPs and MVs that efficiently induced antitumor immune responses in vivo by simultaneously delivering multiple immunostimulatory signals to endogenous T cells. This platform enables the delivery of desired combinations of antitumor immune signals into T cells and NK cells.

Dataset Information

Optimization of critical parameters for coating of polymeric nanoparticles with plasma membrane vesicles by sonication.

Publications

Optimization of critical parameters for coating of polymeric nanoparticles with plasma membrane vesicles by sonication.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets