Intracranial nanomedicine-gel with deep brain-penetration for glioblastoma therapy

Das, Debraj; Narayanan, Dhanya; Ramachandran, Ranjith Karuparambil; Gowd, Genekehal Siddaramana; Manohar, Maneesh; Arumugam, Thennavan; Panikar, Dilip; Nair, Shantikumar V.; Koyakutty, Manzoor

doi:10.1016/j.jconrel.2023.01.085

Cited by 13 publications

(6 citation statements)

References 38 publications

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“…Surgical debulking has emerged as the preferred therapeutic approach for individuals with GBM 41 . The brain parenchymal infiltration and rapid proliferation of GBM cells result in a relapse of the tumor within 2-3 cm from the surgical margin in approximately 90% of patients within 8 months after the operation 42 – 44 . Optimizing surgical resection while preserving the integrity of normal brain function is a challenging goal for neurosurgeons.…”

Section: Discussionmentioning

confidence: 99%

Stimulation of tumoricidal immunity via bacteriotherapy inhibits glioblastoma relapse

Zhang,

Xi,

et al. 2024

Nat Commun

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Glioblastoma multiforme (GBM) is a highly aggressive brain tumor characterized by invasive behavior and a compromised immune response, presenting treatment challenges. Surgical debulking of GBM fails to address its highly infiltrative nature, leaving neoplastic satellites in an environment characterized by impaired immune surveillance, ultimately paving the way for tumor recurrence. Tracking and eradicating residual GBM cells by boosting antitumor immunity is critical for preventing postoperative relapse, but effective immunotherapeutic strategies remain elusive. Here, we report a cavity-injectable bacterium-hydrogel superstructure that targets GBM satellites around the cavity, triggers GBM pyroptosis, and initiates innate and adaptive immune responses, which prevent postoperative GBM relapse in male mice. The immunostimulatory Salmonella delivery vehicles (SDVs) engineered from attenuated Salmonella typhimurium (VNP20009) seek and attack GBM cells. Salmonella lysis-inducing nanocapsules (SLINs), designed to trigger autolysis, are tethered to the SDVs, eliciting antitumor immune response through the intracellular release of bacterial components. Furthermore, SDVs and SLINs administration via intracavitary injection of the ATP-responsive hydrogel can recruit phagocytes and promote antigen presentation, initiating an adaptive immune response. Therefore, our work offers a local bacteriotherapy for stimulating anti-GBM immunity, with potential applicability for patients facing malignancies at a high risk of recurrence.

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Section: Discussionmentioning

confidence: 99%

Stimulation of tumoricidal immunity via bacteriotherapy inhibits glioblastoma relapse

Zhang,

Xi,

et al. 2024

Nat Commun

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“…Alternative administration routes can also benefit from nanoparticles’ properties, such as formulations designed for nose-to-brain drug delivery, where drugs can be directly transported into the brain parenchyma, permeating through the nasal mucosa and reaching the brain through trigeminal and vague nerves [ 194 ]. The intracranial administration after GBM resection is another important strategy being studied, where the formulation – such as hydrogels or scaffolds, is administered directly into the cranial cavity, enhancing the drug concentration into the tumor tissue, that can be further improved with the controlled release property of nanocarriers [ 195 ].…”

Section: Discussionmentioning

confidence: 99%

A receptor-mediated landscape of druggable and targeted nanomaterials for gliomas

Filippo

Carvalho

Duarte

et al. 2023

Materials Today Bio

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“…1−3 The insensitivities of GBM to surgery and postoperative radioand chemotherapy are the main limitations that lead to a 5year survival rate that is less than 8%; thus, the development of GBM therapies is urgently needed. 4,5 Immunotherapy has shown promising outcomes in selected solid tumors. 6,7 However, the substandard immunogenicity of GBM hampers surveillance by the immune system, allowing tumor growth and their evasion of immune responses.…”

Section: Introductionmentioning

confidence: 99%

“…Glioblastoma multiforme (GBM) is recognized as the most prevalent type of primary brain tumor and is known to be difficult to completely resect and has a dismal prognosis. − The insensitivities of GBM to surgery and postoperative radio- and chemotherapy are the main limitations that lead to a 5-year survival rate that is less than 8%; thus, the development of GBM therapies is urgently needed. , Immunotherapy has shown promising outcomes in selected solid tumors. , However, the substandard immunogenicity of GBM hampers surveillance by the immune system, allowing tumor growth and their evasion of immune responses. , Provoking the immunogenicity of GBM is imperative, as it can ameliorate the impaired local immune response, activate adaptive immunity, and bolster the sustained effectiveness of immune cells.…”

Section: Introductionmentioning

confidence: 99%

Blood–Brain Barrier Penetrating Nanovehicles for Interfering with Mitochondrial Electron Flow in Glioblastoma

Zhang,

Xi,

Zhang

et al. 2024

ACS Nano

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Glioblastoma multiforme (GBM) is the most aggressive and lethal form of human brain tumors. Dismantling the suppressed immune microenvironment is an effective therapeutic strategy against GBM; however, GBM does not respond to exogenous immunotherapeutic agents due to low immunogenicity. Manipulating the mitochondrial electron transport chain (ETC) elevates the immunogenicity of GBM, rendering previously immune-evasive tumors highly susceptible to immune surveillance, thereby enhancing tumor immune responsiveness and subsequently activating both innate and adaptive immunity. Here, we report a nanomedicine-based immunotherapeutic approach that targets the mitochondria in GBM cells by utilizing a Trojan-inspired nanovector (ABBPN) that can cross the blood−brain barrier. We propose that the synthetic photosensitizer IrPS can alter mitochondrial electron flow and concurrently interfere with mitochondrial antioxidative mechanisms by delivering si-OGG1 to GBM cells. Our synthesized ABBPN coloaded with IrPS and si-OGG1 (ISA) disrupts mitochondrial electron flow, which inhibits ATP production and induces mitochondrial DNA oxidation, thereby recruiting immune cells and endogenously activating intracranial antitumor immune responses. The results of our study indicate that strategies targeting the mitochondrial ETC have the potential to treat tumors with limited immunogenicity.

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Intracranial nanomedicine-gel with deep brain-penetration for glioblastoma therapy

Cited by 13 publications

References 38 publications

Stimulation of tumoricidal immunity via bacteriotherapy inhibits glioblastoma relapse

Stimulation of tumoricidal immunity via bacteriotherapy inhibits glioblastoma relapse

A receptor-mediated landscape of druggable and targeted nanomaterials for gliomas

Blood–Brain Barrier Penetrating Nanovehicles for Interfering with Mitochondrial Electron Flow in Glioblastoma

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