Nanotherapeutics Overcoming the Blood-Brain Barrier for Glioblastoma Treatment

Tang, Lin; Feng, Yicheng; Gao, Shuang; Mu, Qingchun; Liu, Chaoyong

doi:10.3389/fphar.2021.786700

Cited by 43 publications

(36 citation statements)

References 102 publications

(106 reference statements)

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“…GBM, with the highest malignancy and worst prognosis, is a common neoplasm of the central nervous system [ 32 , 33 ]. Chemotherapy-induced autophagy is a key factor causing drug resistance in tumor cells; however, the exact mechanism that initiates autophagy is not yet fully understood.…”

Section: Discussionmentioning

confidence: 99%

SOCS5 contributes to temozolomide resistance in glioblastoma by regulating Bcl-2-mediated autophagy

Han

Yang

et al. 2022

Bioengineered

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Temozolomide (TMZ) is the primary chemotherapeutic drug for treating glioblastoma (GBM); however, the final clinical outcome is considerably limited by the poor response and resistance to TMZ. Although autophagy is thought to be associated with chemotherapy resistance and cancer cell survival, the precise molecular mechanisms underlying this process remain elusive. The suppressor of cytokine signaling (SOCS) family is widely distributed in vivo and exerts a range of effects on tumors; however, the expression pattern and role of SOCS in GBM remains unknown. In this study, we determined that high SOCS5 expression level was associated with poor prognosis and TMZ resistance in GBM. TMZ induced an increase in SOCS5 expression level and upregulated autophagy during the acquisition of drug resistance. The observed increase in the extent of autophagy was mediated by SOCS5. Mechanistically, SOCS5 enhances the transcription of Bcl-2. Knockdown of SOCS5 inhibited TMZ chemoresistance in GBM cells through the inhibition of Bcl-2 recruited autophagy; upregulation of Bcl-2 blocked this effect. In summary, our findings revealed the involvement and underlying mechanism of SOCS5 in TMZ resistance. SOCS5 plays a critical role in GBM chemoresistance and may serve as a novel prognostic marker and therapeutic target for chemotherapeutically treating drug-resistant GBM.

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Section: Discussionmentioning

confidence: 99%

SOCS5 contributes to temozolomide resistance in glioblastoma by regulating Bcl-2-mediated autophagy

Han

Yang

et al. 2022

Bioengineered

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“…Adjacent vascular endothelial cells form tight junctions and adherent junctions, effectively plugging the clefts between BMECs. Normally, only particles smaller than 1 nm can passively transmit through the pores, thus limiting drug delivery to the brain parenchyma ( 15 ). In the neurovascular unit of the BBB, immune cells such as perivascular macrophages and microglia can also influence BBB function and play important roles in regulating innate and adaptive immunity ( 34 ).…”

Section: Immune Microenvironment and Immunotherapy Strategies Of Glio...mentioning

confidence: 99%

“…The BBB is one of the main factors limiting the therapeutic effect of ICIs. Because of their large molecular size, the concentration of mAbs that can be delivered to the brain is typically 1000 times lower than in blood without compromising biological activity ( 15 ). Galstyan et al.…”

Section: Immune Microenvironment and Immunotherapy Strategies Of Glio...mentioning

confidence: 99%

“…The emergence of nanotechnologies provides a new development direction for the efficient targeted delivery of drugs to overcome physiological barriers and active targeting of specific cell populations, such as tumor cells/immune cell subsets. We have summarized the advances in the development of nanotechnologies to improve drug delivery across the BBB in our previous review ( 15 ). In this review, we will introduce the CNS immune system, immunosuppressive mechanism of GBM, current GBM immunotherapy, and the development of nanomaterials for GBM immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

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Advances in Nanotechnology-Based Immunotherapy for Glioblastoma

2022

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Glioblastoma (GBM) is the most aggressive type of brain tumor. Despite the multimodal therapies, the effectiveness of traditional treatments is not much satisfying. In recent years, immunotherapy has become the focus of tumor treatment. Unlike traditional treatments that directly target tumor cells, immunotherapy uses the body’s immune system to kill tumors. However, due to the severe immunosuppressive microenvironment of GBM, it generally has a poor response to immunotherapy. In addition, the existence of the blood-brain barrier (BBB) also compromises the immunotherapeutic efficacy. Therefore, effective immunotherapy of GBM requires the therapeutic agents to not only efficiently cross the BBB but also relieve the strong immunosuppression of the tumor microenvironment of GBM. In this review, we will first introduce the CNS immune system, immunosuppressive mechanism of GBM, and current GBM immunotherapy strategies. Then, we will discuss the development of nanomaterials for GBM immunotherapy based on different strategies, roughly divided into four parts: immune checkpoint therapy, targeting tumor-associated immune cells, activating immune cells through immunogenic cell death, and combination therapy, to provide new insights for future GBM immunotherapy.

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“…Despite decades of work aimed at developing new therapies to target GBM, its prognosis remains poor. Worldwide, the median length of survival for GBM patients is approximately 8 months, and even surgical intervention followed by rapid initiation of radiation and chemotherapy standard-of-care treatment only increases the median survival length to 14 months [ 1 , 4 ] with a five-year survival rate of 5–10% [ 3 ]. Similarly, the five-year survival rate for individuals with any form of primary malignant brain tumor is just 20% [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Polymeric Nanoparticles in Brain Cancer Therapy: A Review of Current Approaches

et al. 2022

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Translation of novel therapies for brain cancer into clinical practice is of the utmost importance as primary brain tumors are responsible for more than 200,000 deaths worldwide each year. While many research efforts have been aimed at improving survival rates over the years, prognosis for patients with glioblastoma and other primary brain tumors remains poor. Safely delivering chemotherapeutic drugs and other anti-cancer compounds across the blood–brain barrier and directly to tumor cells is perhaps the greatest challenge in treating brain cancer. Polymeric nanoparticles (NPs) are powerful, highly tunable carrier systems that may be able to overcome those obstacles. Several studies have shown appropriately-constructed polymeric NPs cross the blood–brain barrier, increase drug bioavailability, reduce systemic toxicity, and selectively target central nervous system cancer cells. While no studies relating to their use in treating brain cancer are in clinical trials, there is mounting preclinical evidence that polymeric NPs could be beneficial for brain tumor therapy. This review includes a variety of polymeric NPs and how their associated composition, surface modifications, and method of delivery impact their capacity to improve brain tumor therapy.

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Nanotherapeutics Overcoming the Blood-Brain Barrier for Glioblastoma Treatment

Cited by 43 publications

References 102 publications

SOCS5 contributes to temozolomide resistance in glioblastoma by regulating Bcl-2-mediated autophagy

SOCS5 contributes to temozolomide resistance in glioblastoma by regulating Bcl-2-mediated autophagy

Advances in Nanotechnology-Based Immunotherapy for Glioblastoma

Polymeric Nanoparticles in Brain Cancer Therapy: A Review of Current Approaches

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