Synchronous Disintegration of Ferroptosis Defense Axis via Engineered Exosome‐Conjugated Magnetic Nanoparticles for Glioblastoma Therapy

Chen, Xin; Qiu, Wei; Zhao, Rongrong; Duan, Jiazhi; Zhang, Shouji; Pan, Ziwen; Zhao, Shulin; Guo, Qindong; Qi, Yanhua; Wang, Wenhan; Deng, Lin; Ni, Shilei; Sang, Yuanhua; Xue, Hao; Liu, Hong; Li, Gang

doi:10.1002/advs.202105451

Cited by 72 publications

(63 citation statements)

References 53 publications

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“…Coating pure drug self-assembled NPs with endogenous membranes helps delay their circulation time in vivo and improves their targeting to the lesion site. GBM cell membranes, macrophage membranes, and EXO membranes have been used to construct excellent GBM-targeted drug delivery systems. − …”

Section: Resultsmentioning

confidence: 99%

Immune Exosomes Loading Self-Assembled Nanomicelles Traverse the Blood–Brain Barrier for Chemo-immunotherapy against Glioblastoma

Cui

Wang

et al. 2023

ACS Nano

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Effective drug delivery and prevention of postoperative recurrence are significant challenges for current glioblastoma (GBM) treatment. Poor drug delivery is mainly due to the presence of the blood–brain barrier (BBB), and postoperative recurrence is primarily due to the resistance of GBM cells to chemotherapeutic drugs and the presence of an immunosuppressive microenvironment. Herein, a biomimetic nanodrug delivery platform based on endogenous exosomes that could efficiently target the brain without targeting modifications and co-deliver pure drug nanomicelles and immune adjuvants for safe and efficient chemo-immunotherapy against GBM is prepared. Inspired by the self-assembly technology of small molecules, tanshinone IIA (TanIIA) and glycyrrhizic acid (GL), which are the inhibitors of signal transducers and activators of transcription 3 from traditional Chinese medicine (TCM), self-assembled to form TanIIA-GL nanomicelles (TGM). Endogenous serum exosomes are selected to coat the pure drug nanomicelles, and the CpG oligonucleotides, agonists of Toll-like receptor 9, are anchored on the exosome membrane to obtain immune exosomes loaded with TCM self-assembled nanomicelles (CpG-EXO/TGM). Our results demonstrate that CpG-EXO/TGM can bind free transferrin in blood, prolong blood circulation, and maintain intact structures when traversing the BBB and targeting GBM cells. In the GBM microenvironment, the strong anti-GBM effect of CpG-EXO/TGM is mainly attributed to two factors: (i) highly efficient uptake by GBM cells and sufficient intracellular release of drugs to induce apoptosis and (ii) stimulation of dendritic cell maturation and induction of tumor-associated macrophages polarization by CpG oligonucleotides to generate anti-GBM immune responses. Further research found that CpG-EXO/TGM can not only produce better efficacy in combination with temozolomide but also prevent a postoperative recurrence.

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Section: Resultsmentioning

confidence: 99%

Immune Exosomes Loading Self-Assembled Nanomicelles Traverse the Blood–Brain Barrier for Chemo-immunotherapy against Glioblastoma

Cui

Wang

et al. 2023

ACS Nano

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“…Ang, derived from the Kunitz domain of aprotinin, 181 facilitates drug crossing the BBB and targeting glioma cells and has been widely used in treating GBM. [182][183][184][185] nAchR is a receptor transporter highly expressed in both the BBB and neurons and is thus the preferred choice for CNS diseases such as NDs. RVG29 (YTIWMPENPRPGTPC-DIFTNSRGKRASNG), a rabies virus glycoprotein (RVG)-derived peptide containing 29 amino acids, 186 is the most representative ligand peptide for nAchR.…”

Section: Degradation and Clearance In Circulationmentioning

confidence: 99%

Nucleic acid drug vectors for diagnosis and treatment of brain diseases

Lü

Shen

Yang

et al. 2023

Sig Transduct Target Ther

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Nucleic acid drugs have the advantages of rich target selection, simple in design, good and enduring effect. They have been demonstrated to have irreplaceable superiority in brain disease treatment, while vectors are a decisive factor in therapeutic efficacy. Strict physiological barriers, such as degradation and clearance in circulation, blood-brain barrier, cellular uptake, endosome/lysosome barriers, release, obstruct the delivery of nucleic acid drugs to the brain by the vectors. Nucleic acid drugs against a single target are inefficient in treating brain diseases of complex pathogenesis. Differences between individual patients lead to severe uncertainties in brain disease treatment with nucleic acid drugs. In this Review, we briefly summarize the classification of nucleic acid drugs. Next, we discuss physiological barriers during drug delivery and universal coping strategies and introduce the application methods of these universal strategies to nucleic acid drug vectors. Subsequently, we explore nucleic acid drug-based multidrug regimens for the combination treatment of brain diseases and the construction of the corresponding vectors. In the following, we address the feasibility of patient stratification and personalized therapy through diagnostic information from medical imaging and the manner of introducing contrast agents into vectors. Finally, we take a perspective on the future feasibility and remaining challenges of vector-based integrated diagnosis and gene therapy for brain diseases.

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“…Exosomes are classified as a group of extracellular vesicles ranging from 30–150 nm containing different materials including protein, lipid, and nucleic acid, depending on their origin cells and having significant roles in intercellular communication and also treating a wide range of diseases ( Broekman et al, 2018 ; Pegtel and Gould, 2019 ; Zhai et al, 2020 ). Moreover, they pose the advantage of crossing BBB, making them good choices for treating brain diseases ( Li et al, 2022b ). Because of their BBB penetration features, they could help design novel therapeutic approaches targeting GBM.…”

Section: An Overview On Cm-coating Technologymentioning

confidence: 99%

The role of cell membrane-coated nanoparticles as a novel treatment approach in glioblastoma

Allami

Heidari²,

Rezaei³

2023

Front. Mol. Biosci.

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Glioblastoma multiform (GBM) is the most prevalent and deadliest primary brain malignancy in adults, whose median survival rate does not exceed 15 months after diagnosis. The conventional treatment of GBM, including maximal safe surgery followed by chemotherapy and radiotherapy, usually cannot lead to notable improvements in the disease prognosis and the tumor always recurs. Many GBM characteristics make its treatment challenging. The most important ones are the impermeability of the blood-brain barrier (BBB), preventing chemotherapeutic drugs from reaching in adequate amounts to the tumor site, intratumoral heterogeneity, and roles of glioblastoma stem cells (GSCs). To overcome these barriers, the recently-developed drug-carrying approach using nanoparticles (NPs) may play a significant role. NPs are tiny particles, usually less than 100 nm showing various diagnostic and therapeutic medical applications. In this regard, cell membrane (CM)-coated NPs demonstrated several promising effects in GBM in pre-clinical studies. They benefit from fewer adverse effects due to their specific targeting of tumor cells, biocompatibility because of their CM surfaces, prolonged half-life, easy penetrating of the BBB, and escaping from the immune reaction, making them an attractive option for GBM treatment. To date, CM-coated NPs have been applied to enhance the effectiveness of major therapeutic approaches in GBM treatment, including chemotherapy, immunotherapy, gene therapy, and photo-based therapies. Despite the promising results in pre-clinical studies regarding the effectiveness of CM-coated NPs in GBM, significant barriers like high expenses, complex preparation processes, and unknown long-term effects still hinder its mass production for the clinic. In this regard, the current study aims to provide an overview of different characteristics of CM-coated NPs and comprehensively investigate their application as a novel treatment approach in GBM.

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Synchronous Disintegration of Ferroptosis Defense Axis via Engineered Exosome‐Conjugated Magnetic Nanoparticles for Glioblastoma Therapy

Cited by 72 publications

References 53 publications

Immune Exosomes Loading Self-Assembled Nanomicelles Traverse the Blood–Brain Barrier for Chemo-immunotherapy against Glioblastoma

Immune Exosomes Loading Self-Assembled Nanomicelles Traverse the Blood–Brain Barrier for Chemo-immunotherapy against Glioblastoma

Nucleic acid drug vectors for diagnosis and treatment of brain diseases

The role of cell membrane-coated nanoparticles as a novel treatment approach in glioblastoma

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