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An erythrocyte membrane coated mimetic nano-platform for chemo-phototherapy and multimodal imaging.

ABSTRACT: The tumor variability and low efficiency associated with conventional chemical drugs provide an impetus to develop drug-carrying systems with targeted accumulation and controllable release behavior. Herein, DOX-loaded Prussian blue (PB) nano-composites are developed after coating with erythrocyte membrane (EM) and modifying with folic acid (FA). In these nano-composites, PB nanoparticles mixture with different shapes were adopted to improve the photothermal performance, which is highly helpful for cancer photothermal ablation and controllable drug release. In addition, the nano-composites were endowed with high biocompatibility, immune evading capacity, pH-/photo-responsive release behavior, and markedly prolonged blood circulation time, which was reflected by a 99.6% cervical tumor growth inhibition value (TGI) in vivo. Meanwhile, they functioned as multimodal bioimaging agents for photothermal, fluorescence, and photoacoustic imaging of tumors. The reported strategy can be applied for personalized therapy of various tumors by modifying the tumor-targeting molecule on the surface of nanoparticles.

SUBMITTER: Xiao F

PROVIDER: S-EPMC9070788 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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An erythrocyte membrane coated mimetic nano-platform for chemo-phototherapy and multimodal imaging.

Xiao Feng F Fan Jialong J Tong Chunyi C Xiao Chang C Wang Zhou Z Liu Bin B Daniyal Muhammad M Wang Wei W

RSC advances 20190904 48

The tumor variability and low efficiency associated with conventional chemical drugs provide an impetus to develop drug-carrying systems with targeted accumulation and controllable release behavior. Herein, DOX-loaded Prussian blue (PB) nano-composites are developed after coating with erythrocyte membrane (EM) and modifying with folic acid (FA). In these nano-composites, PB nanoparticles mixture with different shapes were adopted to improve the photothermal performance, which is highly helpful f ...[more]

PMID: 35530495

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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

An erythrocyte membrane coated mimetic nano-platform for chemo-phototherapy and multimodal imaging.

Publications

An erythrocyte membrane coated mimetic nano-platform for chemo-phototherapy and multimodal imaging.

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