Albumin-stabilized manganese-based nanocomposites with sensitive tumor microenvironment responsivity and their application for efficient SiRNA delivery in brain tumors

Xu, Kai; Zhao, Zhenghuan; Zhang, Junfeng; Xue, Wei; Tong, Haipeng; Liu, Heng; Zhang, Weiguo

doi:10.1039/c9tb02341k

Cited by 25 publications

(13 citation statements)

References 43 publications

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“…Fluorescence spectroscopic analysis of BSA after treatment with graded Mn 2+ concentrations showed that the BSA-characteristic emission at 336 nm gradually decreased with increasing Mn 2+ feeding ratios (Fig. 2g ), which was ascribed to the binding between Mn 2+ and aspartic acid or histidine residues in BSA and consistent with the observations in previous reports 34 – 36 . According to the DLS analysis, the hydrodynamic size of BSA-Man@Mn 2+ was around 8 nm in aqueous solution (Fig.…”

Section: Resultssupporting

confidence: 90%

A protein-based cGAS-STING nanoagonist enhances T cell-mediated anti-tumor immune responses

et al. 2022

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AbstractcGAS-STING pathway is a key DNA-sensing machinery and emerges as a promising target to overcome the immunoresistance of solid tumors. Here we describe a bovine serum albumin (BSA)/ferritin-based nanoagonist incorporating manganese (II) ions and β-lapachone, which cooperatively activates cGAS-STING signaling in dendritic cells (DCs) to elicit robust adaptive antitumor immunity. Mn2+-anchored mannose-modified BSAs and β-lapachone-loaded ferritins are crosslinked to afford bioresponsive protein nanoassemblies, which dissociate into monodispersive protein units in acidic perivascular tumor microenvironment (TME), thus enabling enhanced tumor penetration and spatiotemporally controlled Mn2+ and β-lapachone delivery to DCs and tumor cells, respectively. β-lapachone causes immunogenic tumor cell apoptosis and releases abundant dsDNA into TME, while Mn2+ enhances the sensitivity of cGAS to dsDNA and augments STING signaling to trigger downstream immunostimulatory signals. The cGAS-STING nanoagonist enhances the tumor-specific T cell-mediated immune response against poorly immunogenic solid tumors in vivo, offering a robust approach for immunotherapy in the clinics.

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Section: Resultssupporting

confidence: 90%

A protein-based cGAS-STING nanoagonist enhances T cell-mediated anti-tumor immune responses

et al. 2022

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“…Moreover, the designed NPs showed minimal toxicity against normal human astrocytes [ 173 , 174 ]. Another recent study reported the enhancement of metallic NPs stability in siRNAs delivery and glioblastoma treatment via decoration with albumin [ 175 ]. In this regard, bovine serum albumin-stabilized manganese-based NPs were fabricated to efficiently deliver VEGF-siRNAs in brain tumor treatment.…”

Section: Modern Rna-based Therapeutic Modalitiesmentioning

confidence: 99%

Molecular Engines, Therapeutic Targets, and Challenges in Pediatric Brain Tumors: A Special Emphasis on Hydrogen Sulfide and RNA-Based Nano-Delivery

Fahmy¹,

Dawoud

Zeinelabdeen

et al. 2022

Cancers

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Pediatric brain tumors represent a formidable challenge in the field of oncology. Pediatric brain tumors are sub-classified into several molecular sub-types, where each one is characterized by an array of hyperactivated oncogenic molecular engines. However, there have been great efforts dedicated to portray the involved signaling pathways driving pediatric brain tumors. Yet, a full understanding of the intertwined oncogenic pathways involved is still obscure. In this review, the authors shed light on novel therapeutic targets tailored for several sub-types of pediatric brain tumors and point out the limitations of such therapeutic approaches. Hydrogen Sulfide (H2S) has recently been cast as an oncogenic driver in several solid malignancies, yet its role in brain tumors is still under investigation. The authors also highlight the possible involvement of H2S in pediatric brain tumors and propose promising brain-delivery strategies for the sake of achieving better therapeutic results for brain tumors patients.Abstract: Pediatric primary brain tumors represent a real challenge in the oncology arena. Besides the psychosocial burden, brain tumors are considered one of the most difficult-to-treat malignancies due to their sophisticated cellular and molecular pathophysiology. Notwithstanding the advances in research and the substantial efforts to develop a suitable therapy, a full understanding of the molecular pathways involved in primary brain tumors is still demanded. On the other hand, the physiological nature of the blood–brain barrier (BBB) limits the efficiency of many available treatments, including molecular therapeutic approaches. Hydrogen Sulfide (H2S), as a member of the gasotransmitters family, and its synthesizing machinery have represented promising molecular targets for plentiful cancer types. However, its role in primary brain tumors, generally, and pediatric types, particularly, is barely investigated. In this review, the authors shed the light on the novel role of hydrogen sulfide (H2S) as a prominent player in pediatric brain tumor pathophysiology and its potential as a therapeutic avenue for brain tumors. In addition, the review also focuses on the challenges and opportunities of several molecular targeting approaches and proposes promising brain-delivery strategies for the sake of achieving better therapeutic results for brain tumor patients.

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“…Mn(iii) and Mn(iv) integrated nanocomposites were prepared with good stability and excellent biocompatibility. These NPs show superior advantages of siRNA delivery in gliomas, including increasing tumor uptake, improving tumor accumulation, and enhancing the therapeutic effect by adjusting TME (Xu et al, 2020).…”

Section: Inorganic Nanoparticlesmentioning

confidence: 99%

Small Interfering RNA for Gliomas Treatment: Overcoming Hurdles in Delivery

Teng

et al. 2022

Front. Cell Dev. Biol.

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Gliomas are central nervous system tumors originating from glial cells, whose incidence and mortality rise in coming years. The current treatment of gliomas is surgery combined with chemotherapy or radiotherapy. However, developing therapeutic resistance is one of the significant challenges. Recent research suggested that small interfering RNA (siRNA) has excellent potential as a therapeutic to silence genes that are significantly involved in the manipulation of gliomas’ malignant phenotypes, including proliferation, invasion, metastasis, therapy resistance, and immune escape. However, it is challenging to deliver the naked siRNA to the action site in the cells of target tissues. Therefore, it is urgent to develop delivery strategies to transport siRNA to achieve the optimal silencing effect of the target gene. However, there is no systematic discussion about siRNAs’ clinical potential and delivery strategies in gliomas. This review mainly discusses siRNAs’ delivery strategies, especially nanotechnology-based delivery systems, as a potential glioma therapy. Moreover, we envisage the future orientation and challenges in translating these findings into clinical applications.

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Albumin-stabilized manganese-based nanocomposites with sensitive tumor microenvironment responsivity and their application for efficient SiRNA delivery in brain tumors

Abstract: Synthesis of Mn(iii)/Mn(iv) integrated nanocomposites to realize sensitive MRI performance in weakly acidic environments and efficient siRNA delivery.

Cited by 25 publications

References 43 publications

A protein-based cGAS-STING nanoagonist enhances T cell-mediated anti-tumor immune responses

A protein-based cGAS-STING nanoagonist enhances T cell-mediated anti-tumor immune responses

Molecular Engines, Therapeutic Targets, and Challenges in Pediatric Brain Tumors: A Special Emphasis on Hydrogen Sulfide and RNA-Based Nano-Delivery

Small Interfering RNA for Gliomas Treatment: Overcoming Hurdles in Delivery

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