Engineering magnetotactic bacteria MVs to synergize chemotherapy, ferroptosis and immunotherapy for augmented antitumor therapy

Jiang, Gexuan; Xiang, Zhichu; Fang, Qiaojun

doi:10.1039/d3nh00061c

Cited by 6 publications

(3 citation statements)

References 51 publications

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“…This hybrid nanoformulation further enhanced tumor cytotoxicity and suppressed tumor development and metastatic nodules in several preclinical mouse tumor models [ 108 ]. DSPE-PEG-RGD-based targeting was also employed on bEVs from the magnetotactic bacterium Magnetospirillum gryphiswaldense , cultured in the presence of iron and doxorubicin to generate bEVs loaded with all 3 of these components [ 109 ]. These bEVs resulted in ferroptosis of targeted cancer cells and immune activation and displayed preclinical therapeutic efficacy in primary and metastic breast cancer models [ 109 ].…”

Section: Microbiome Revelations Spur Interest In Bugs-as-drugs For Ca...mentioning

confidence: 99%

“…DSPE-PEG-RGD-based targeting was also employed on bEVs from the magnetotactic bacterium Magnetospirillum gryphiswaldense , cultured in the presence of iron and doxorubicin to generate bEVs loaded with all 3 of these components [ 109 ]. These bEVs resulted in ferroptosis of targeted cancer cells and immune activation and displayed preclinical therapeutic efficacy in primary and metastic breast cancer models [ 109 ]. Cui et al also generated a hybrid nanoformulation consisting of miRNA encapsulated in a zeolitic imidazolate framework-8 and then coated with E. coli bEVs expressing surface PD-1/Cytolysin A fusion protein as a tumor-targeting ligand [ 110 ].…”

Section: Microbiome Revelations Spur Interest In Bugs-as-drugs For Ca...mentioning

confidence: 99%

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Harnessing Bacterial Extracellular Vesicle Immune Effects for Cancer Therapy

Karaman,

Pathak,

Bayik

et al. 2024

PAI

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There are a growing number of studies linking the composition of the human microbiome to disease states and treatment responses, especially in the context of cancer. This has raised significant interest in developing microbes and microbial products as cancer immunotherapeutics that mimic or recapitulate the beneficial effects of host-microbe interactions. Bacterial extracellular vesicles (bEVs) are nano-sized, membrane-bound particles secreted by essentially all bacteria species and contain a diverse bioactive cargo of the producing cell. They have a fundamental role in facilitating interactions among cells of the same species, different microbial species, and even with multicellular host organisms in the context of colonization (microbiome) and infection. The interaction of bEVs with the immune system has been studied extensively in the context of infection and suggests that bEV effects depend largely on the producing species. They thus provide functional diversity, while also being nonreplicative, having inherent cell-targeting qualities, and potentially overcoming natural barriers. These characteristics make them highly appealing for development as cancer immunotherapeutics. Both natively secreted and engineered bEVs are now being investigated for their application as immunotherapeutics, vaccines, drug delivery vehicles, and combinations of the above, with promising early results. This suggests that both the intrinsic immunomodulatory properties of bEVs and their ability to be modified could be harnessed for the development of next-generation microbe-inspired therapies. Nonetheless, there remain major outstanding questions regarding how the observed preclinical effectiveness will translate from murine models to primates, and humans in particular. Moreover, research into the pharmacology, toxicology, and mass manufacturing of this potential novel therapeutic platform is still at early stages. In this review, we highlight the breadth of bEV interactions with host cells, focusing on immunologic effects as the main mechanism of action of bEVs currently in preclinical development. We review the literature on ongoing efforts to develop natively secreted and engineered bEVs from a variety of bacterial species for cancer therapy and finally discuss efforts to overcome outstanding challenges that remain for clinical translation.

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Section: Microbiome Revelations Spur Interest In Bugs-as-drugs For Ca...mentioning

confidence: 99%

Section: Microbiome Revelations Spur Interest In Bugs-as-drugs For Ca...mentioning

confidence: 99%

Harnessing Bacterial Extracellular Vesicle Immune Effects for Cancer Therapy

Karaman,

Pathak,

Bayik

et al. 2024

PAI

View full text Add to dashboard Cite

show abstract

“…A major cause of recurrence, metastasis and drug resistance in breast cancers lacking effective anti-hormonal targets is the formation of immunosuppression in the tumor microenvironment, and clinical breast cancer treatment strategies have shown great interest in single agent co-immunosuppressive therapy [ 110 ]. Crosstalk between FBXW7 and related binding proteins regulates immune cell numbers, metastasis, and the premetastatic niche, playing a role in breast cancer immunosuppression [ 111 , 112 ] (Fig.…”

Section: Crosstalk Between Fbxw7 and Binding Proteins In Bc Progressionmentioning

confidence: 99%

FBXW7 in breast cancer: mechanism of action and therapeutic potential

Chen,

Leng,

Guo

et al. 2023

J Exp Clin Cancer Res

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Breast cancer is one of the frequent tumors that seriously endanger the physical and mental well-being in women. F-box and WD repeat domain-containing 7 (FBXW7) is a neoplastic repressor. Serving as a substrate recognition element for ubiquitin ligase, FBXW7 participates in the ubiquitin–proteasome system and is typically in charge of the ubiquitination and destruction of crucial oncogenic proteins, further performing a paramount role in cell differentiation, apoptosis and metabolic processes. Low levels of FBXW7 cause abnormal stability of pertinent substrates, mutations and/or deletions in the FBXW7 gene have been reported to correlate with breast cancer malignant progression and chemoresistance. Given the lack of an effective solution to breast cancer's clinical drug resistance dilemma, elucidating FBXW7's mechanism of action could provide a theoretical basis for targeted drug exploration. Therefore, in this review, we focused on FBXW7's role in a range of breast cancer malignant behaviors and summarized the pertinent cellular targets, signaling pathways, as well as the mechanisms regulating FBXW7 expression. We also proposed novel perspectives for the exploitation of alternative therapies and specific tumor markers for breast cancer by therapeutic strategies aiming at FBXW7.

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Nanoformula Design for Inducing Non‐Apoptotic Cell Death Regulation: A Powerful Booster for Cancer Immunotherapy

Hu,

Yu,

et al. 2024

Adv Healthcare Materials

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Cancer treatment has witnessed revolutionary advancements marked by the emergence of immunotherapy, specifically immune checkpoint blockade (ICB). However, the inherent low immunogenicity of tumor cells and the intricate immunosuppressive network within the tumor microenvironment (TME) pose significant challenges to the further development of immunotherapy. Nanotechnology has ushered in unprecedented opportunities and vast prospects for tumor immunotherapy. Nevertheless, traditional nano‐formulations often rely on inducing apoptosis to kill cancer cells, which encounters the issue of immune silencing, hindering effective tumor immune activation.The non‐apoptotic modes of regulated cell death (RCD), including pyroptosis, ferroptosis, autophagy, necroptosis, and cuproptosis, have gradually garnered attention. These non‐apoptotic cell death pathways can induce effective immunogenic cell death (ICD), enhancing cancer immunotherapy. This review comprehensively explores advanced nano‐formulation design strategies and their applications in enhancing cancer immunotherapy by promoting non‐apoptotic RCD in recent years. It also discusses the potential advantages of these strategies in inducing tumor‐specific non‐apoptotic RCD. By deeply understanding the significance of non‐apoptotic RCD in synergistic cancer immunotherapy, this article provides valuable insights for developing more advanced nano‐delivery systems that can robustly induce highly immunogenic non‐apoptotic modes, offering novel research and development avenues to address the clinical challenges encountered by immunotherapy represented by ICB.

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Engineering magnetotactic bacteria MVs to synergize chemotherapy, ferroptosis and immunotherapy for augmented antitumor therapy

Abstract: A magnetotactic bacteria membrane vesicle-based nanovaccine integrating chemotherapy/immunotherapy/ferroptosis-inducing capability in one, may provide an efficacious treatment option for enhancing tumor synergistic therapy.

Cited by 6 publications

References 51 publications

Harnessing Bacterial Extracellular Vesicle Immune Effects for Cancer Therapy

Harnessing Bacterial Extracellular Vesicle Immune Effects for Cancer Therapy

FBXW7 in breast cancer: mechanism of action and therapeutic potential

Nanoformula Design for Inducing Non‐Apoptotic Cell Death Regulation: A Powerful Booster for Cancer Immunotherapy

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