Nanotherapeutic treatment of the invasive glioblastoma tumor microenvironment

Pandey, Nikhil; Anastasiadis, Pavlos; Carney, Christine P.; Kanvinde, Pranjali; Woodworth, Graeme F.; Winkles, Jeffrey A.; Kim, Anthony J.

doi:10.1016/j.addr.2022.114415

Cited by 28 publications

(24 citation statements)

References 277 publications

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“…Endogenous transport processes such as receptor-mediated transcytosis (RMT), carrier-mediated transcytosis, adsorptive-mediated transcytosis, and cell-mediated transcytosis can be utilized to deliver the nanoparticles across the BBB. Among these RMT is primarily exploited by utilizing nanoparticles modified with various ligands that can bind specific receptors on the BBB [ 141 , 142 ]. These receptors include transferrin receptor, low-density lipoprotein receptor, low-density lipoprotein receptor-related protein, folate receptor, lactoferrin receptor, insulin receptor, diphtheria toxin receptor, neonatal Fc receptor, nicotinic acetylcholine receptor, nucleolin receptor, scavenger receptor class B type, and leptin receptor [ 141 ].…”

Section: Strategies To Achieve Targeted Delivery Of Tkismentioning

confidence: 99%

Tyrosine Kinase Inhibitors for Glioblastoma Multiforme: Challenges and Opportunities for Drug Delivery

Brar

Jose

et al. 2022

Pharmaceutics

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Glioblastoma multiforme (GBM) is an aggressive brain tumor with high mortality rates. Due to its invasiveness, heterogeneity, and incomplete resection, the treatment is very challenging. Targeted therapies such as tyrosine kinase inhibitors (TKIs) have great potential for GBM treatment, however, their efficacy is primarily limited by poor brain distribution due to the presence of the blood–brain barrier (BBB). This review focuses on the potential of TKIs in GBM therapy and provides an insight into the reasons behind unsuccessful clinical trials of TKIs in GBM despite the success in treating other cancer types. The main section is dedicated to the use of promising drug delivery strategies for targeted delivery to brain tumors. Use of brain targeted delivery strategies can help enhance the efficacy of TKIs in GBM. Among various drug delivery approaches used to bypass or cross BBB, utilizing nanocarriers is a promising strategy to augment the pharmacokinetic properties of TKIs and overcome their limitations. This is because of their advantages such as the ability to cross BBB, chemical stabilization of drug in circulation, passive or active targeting of tumor, modulation of drug release from the carrier, and the possibility to be delivered via non-invasive intranasal route.

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Section: Strategies To Achieve Targeted Delivery Of Tkismentioning

confidence: 99%

Tyrosine Kinase Inhibitors for Glioblastoma Multiforme: Challenges and Opportunities for Drug Delivery

Brar

Jose

et al. 2022

Pharmaceutics

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“…Invasive glioma cells are resistant to clinical standard-of-care chemotherapy, along with radiation [ 15 ]. The emerging molecular target implicated in invasive glioma biology is the TNF receptor superfamily member named fibroblast growth factor-inducible 14 (Fn14) [ 5 , 38 ]. Additional, mural-like tumor cells differentiate from GSCs.…”

Section: Resultsmentioning

confidence: 99%

“…Recently, nano-assisted therapies such as nano-immunotherapy, nano-stem cell therapy, and nano-gene therapy have been investigated for brain cancer treatment [ 5 , 6 , 7 ]. The safety of GBM treatments has been considered as a priority.…”

Section: Introductionmentioning

confidence: 99%

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Hydrogel on a Smart Nanomaterial Interface to Carry Therapeutics for Digitalized Glioma Treatment

Zhao

Javed

Tian

et al. 2022

Gels

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Glioma is considered the primary brain tumor to cause brain illnesses, and it is difficult to treat and shows resistance to various routine therapeutics. The most common treatments to cure glioma are the surgical removal of tumors followed by adjuvant chemotherapy and radiation therapy. The latest biocompatible interfaces have been incorporated into therapeutic modalities such as the targeted delivery of drugs using hydrogels to treat and manage brain glioma. This review illustrates the applications of the multimodal hydrogel as the carrier of therapeutics, gene therapy, therapeutic tactics, and glioma devices. The scientific articles were retrieved from 2019 to 2022 on Google Scholar and the Scopus database and screened to determine whether they were suitable for review. The 20 articles that fit the study are summarized in this review. These studies indicated that the sizes of the hydrogel range from 28 nm to 500 nm. There are 16 out of 20 articles that also explain the post-surgical application of hydrogels, and 13 out of 20 articles are employed in 3D culture and other structural manifestations of hydrogels. The pros of the hydrogel include the quick formulation for a sufficient filling of irregular damage sites, solubilizing hydrophobic drugs, continuously slowing drug release, provision of a 3D cell growth environment, improving efficacy, targetability of soluble biomolecules, increasing patient compliance, and decreased side effects. The cons of the hydrogel include difficult real-time monitoring, genetic manipulations, the cumbersome synchronized release of components, and lack of safety data. The prospects of the hydrogel may include the development of electronic hydrogel sensors that can be used to enhance guidance for the precise targeting patterns using patient-specific pathological idiosyncrasies. This technology has the potential to revolutionize the precision medicine approaches that would aid in the early detection and management of solid brain tumors.

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“…In Addition to current therapy, immunotherapy and targeted therapy are also promising fields for further study 7 , 8 . In regard to medicines, bevacizumab was once believed to be a promising therapeutic agent and was approved by the US Food and Drug Administration (FDA) in 2009.…”

Section: Introductionmentioning

confidence: 99%

Prodigiosin inhibits the proliferation of glioblastoma by regulating the KIAA1524/PP2A signaling pathway

Zhao

Gao

Ning

et al. 2022

Sci Rep

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Prodigiosin (PG), a member of a family of natural red pigments produced by a variety of bacteria, was first discovered in Serratia marcescens. PG has been reported to have an apoptosis-inducing effect in many cancers, such as lymphoma, colon cancer and nasopharyngeal carcinoma. For this study, we used three glioblastoma (GBM) cell lines (LN229, U251 and A172) to explore the effect of prodigiosin on GBM cells. A CCK8 assay was used to evaluate cell viability. We determinedthe cell cycle distribution by flow cytometry and measured proliferation by an EdU incorporation assay. The expression of different molecules was investigated by western blotting and RT-PCR. We further confirmed our results by plasmid transfection and lentiviral transduction. The LN229 xenograft model was used to study the effect of prodigiosin in vivo. We confirmed that prodigiosin played an anticancer role in several GBM cell lines through the KIAA1524/PP2A/Akt signalling pathway. Prodigiosin inhibited the protein expression of KIAA1524 by suppressing its transcription, which led to activation of PP2A. Afterward, PP2A inhibited the phosphorylation of Akt, thereby inducing increased expression of p53/p21. Furthermore, it was verified that prodigiosin inhibited the KIAA1524/PP2A/Akt axis in vivo in the LN229 xenograft model. These data improve the understanding of the anticancer effects of prodigiosin and further highlight the potential of prodigiosin for the development of anti-glioma drugs.

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Nanotherapeutic treatment of the invasive glioblastoma tumor microenvironment

Cited by 28 publications

References 277 publications

Tyrosine Kinase Inhibitors for Glioblastoma Multiforme: Challenges and Opportunities for Drug Delivery

Tyrosine Kinase Inhibitors for Glioblastoma Multiforme: Challenges and Opportunities for Drug Delivery

Hydrogel on a Smart Nanomaterial Interface to Carry Therapeutics for Digitalized Glioma Treatment

Prodigiosin inhibits the proliferation of glioblastoma by regulating the KIAA1524/PP2A signaling pathway

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