Enhancement of Therapies for Glioblastoma (GBM) Using Nanoparticle-based Delivery Systems

Wiwatchaitawee, Kanawat; Quarterman, Juliana C.; Geary, Sean M.; Salem, Aliasger K.

doi:10.1208/s12249-021-01928-9

Cited by 36 publications

(21 citation statements)

References 179 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…GBM is one of the most aggressive forms of brain cancer that affects thousands of people and is notable for its poor prognoses. Since current strategies lack specificity, which leads to toxicity in healthy tissues and does not inhibit recurrences, targeted nanomedicines (NMeds) are being widely investigated as promising new tools, as demonstrated by an abundance of reviews in the last two years [ 70 , 71 , 72 , 73 , 74 , 75 , 76 ]. One of the most important aspects to consider when optimising a targeted NMed is selecting an appropriate targeting ligand.…”

Section: Discussionmentioning

confidence: 99%

Glioblastoma Multiforme Selective Nanomedicines for Improved Anti-Cancer Treatments

et al. 2022

View full text Add to dashboard Cite

Glioblastoma Multiforme (GBM) is a devastating disease with a low survival rate and few efficacious treatment options. The fast growth, late diagnostics, and off-target toxicity of currently used drugs represent major barriers that need to be overcome to provide a viable cure. Nanomedicines (NMeds) offer a way to overcome these pitfalls by protecting and loading drugs, increasing blood half-life, and being targetable with specific ligands on their surface. In this study, the FDA-approved polymer poly (lactic-co-glycolic) acid was used to optimise NMeds that were surface modified with a series of potential GBM-specific ligands. The NMeds were fully characterised for their physical and chemical properties, and then in vitro testing was performed to evaluate cell uptake and GBM cell specificity. While all targeted NMeds showed improved uptake, only those decorated with the-cell surface vimentin antibody M08 showed specificity for GBM over healthy cells. Finally, the most promising targeted NMed candidate was loaded with the well-known chemotherapeutic, paclitaxel, to confirm targeting and therapeutic effects in C6 GBM cells. These results demonstrate the importance of using well-optimised NMeds targeted with novel ligands to advance delivery and pharmaceutical effects against diseased cells while minimising the risk for nearby healthy cells.

show abstract

Section: Discussionmentioning

confidence: 99%

Glioblastoma Multiforme Selective Nanomedicines for Improved Anti-Cancer Treatments

et al. 2022

View full text Add to dashboard Cite

show abstract

“…However, there is little consensus on the physiochemical constraints that govern “optimal” BBB penetration and drug delivery for GBM. For example, some studies report better active passage through the BBB with neutral structures ( Wiwatchaitawee et al, 2021 ), while anionic nanoparticles show dose-dependent effects on BBB penetration ( Lockman et al, 2004 ). On the contrary, cationic drug vehicles can facilitate brain uptake by adsorptive-mediated transcytosis or endocytosis ( Vieira and Gamarra, 2016 ) ( Joshi et al, 2014 ), while amphiphilic nanoparticles can take advantage of active and passive accumulation ( He et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Boosting Natural Killer Cell Therapies in Glioblastoma Multiforme Using Supramolecular Cationic Inhibitors of Heat Shock Protein 90

Saha

Vliet²,

Cui³

et al. 2021

Front. Mol. Biosci.

View full text Add to dashboard Cite

Allogeneic natural killer (aNK) cell adoptive therapy has the potential to dramatically impact clinical outcomes of glioblastoma multiforme (GBM). However, in order to exert therapeutic activity, NK cells require tumor expression of ligands for activating receptors, such as MHC Class I peptide A/B (MICA/B) and ULBPs. Here, we describe the use of a blood–brain barrier (BBB) permissive supramolecular cationic drug vehicle comprising an inhibitor of the chaperone heat shock protein 90 (Hsp90), which sustains a cytotoxic effect on GBM cells, boosts the expression of MICA/B and ULBPs on the residual population, and augments the activity of clinical-grade aNK cells (GTA002). First, we identify Hsp90 mRNA transcription and gain of function as significantly upregulated in GBM compared to other central nervous system tumors. Through a rational chemical design, we optimize a radicicol supramolecular prodrug containing cationic excipients, SCI-101, which displays >2-fold increase in relative BBB penetration compared to less cationic formulations in organoids, in vitro. Using 2D and 3D biological models, we confirm SCI-101 sustains GBM cytotoxicity 72 h after drug removal and induces cell surface MICA/B protein and ULBP mRNA up to 200% in residual tumor cells compared to the naked drug alone without augmenting the shedding of MICA/B, in vitro. Finally, we generate and test the sequential administration of SCI-101 with a clinical aNK cell therapy, GTA002, differentiated and expanded from healthy umbilical cord blood CD34+ hematopoietic stem cells. Using a longitudinal in vitro model, we demonstrate >350% relative cell killing is achieved in SCI-101–treated cell lines compared to vehicle controls. In summary, these data provide a first-of-its-kind BBB-penetrating, long-acting inhibitor of Hsp90 with monotherapy efficacy, which improves response to aNK cells and thus may rapidly alter the treatment paradigm for patients with GBM.

show abstract

“…The combination of FeNP-based MHT with local injection of nano-adjuvants and systemic injection of anti-CTLA4 can lead to systemic therapeutic responses to inhibit tumor metastasis (75). In addition, nano-drugs, especially NPs combined with hyperthermia, are being studied as potential ways to enhance tumor drug delivery in patients with GBM (105).…”

Section: Brain Cancermentioning

confidence: 99%

Hyperthermia combined with immune checkpoint inhibitor therapy in the treatment of primary and metastatic tumors

Yang

Gao

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

According to the difference in temperature, thermotherapy can be divided into thermal ablation and mild hyperthermia. The main advantage of thermal ablation is that it can efficiently target tumors in situ, while mild hyperthermia has a good inhibitory effect on distant metastasis. There are some similarities and differences between the two therapies with respect to inducing anti-tumor immune responses, but neither of them results in sustained systemic immunity. Malignant tumors (such as breast cancer, pancreatic cancer, nasopharyngeal carcinoma, and brain cancer) are recurrent, highly metastatic, and highly invasive even after treatment, hence a single therapy rarely resolves the clinical issues. A more effective and comprehensive treatment strategy using a combination of hyperthermia and immune checkpoint inhibitor (ICI) therapies has gained attention. This paper summarizes the relevant preclinical and clinical studies on hyperthermia combined with ICI therapies and compares the efficacy of two types of hyperthermia combined with ICIs, in order to provide a better treatment for the recurrence and metastasis of clinically malignant tumors.

show abstract

Enhancement of Therapies for Glioblastoma (GBM) Using Nanoparticle-based Delivery Systems

Cited by 36 publications

References 179 publications

Glioblastoma Multiforme Selective Nanomedicines for Improved Anti-Cancer Treatments

Glioblastoma Multiforme Selective Nanomedicines for Improved Anti-Cancer Treatments

Boosting Natural Killer Cell Therapies in Glioblastoma Multiforme Using Supramolecular Cationic Inhibitors of Heat Shock Protein 90

Hyperthermia combined with immune checkpoint inhibitor therapy in the treatment of primary and metastatic tumors

Contact Info

Product

Resources

About