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Neurosurgical application of olaparib from a thermo-responsive paste potentiates DNA damage to prolong survival in malignant glioma (2024)
Journal Article
Serra, R., Smith, S. J., Rowlinson, J., Gorelick, N., Moloney, C., McCrorie, P., Veal, G. J., Berry, P., Chalmers, A. J., Suk, I., Shakesheff, K. M., Alexander, C., Grundy, R. G., Brem, H., Tyler, B. M., & Rahman, R. (2024). Neurosurgical application of olaparib from a thermo-responsive paste potentiates DNA damage to prolong survival in malignant glioma. British Journal of Cancer, https://doi.org/10.1038/s41416-024-02878-2

Background: There is increased pan-cancer specific interest in repurposing the poly adenosine diphosphate-ribose polymerase-1 (PARP-1) inhibitor, olaparib, for newly diagnosed or recurrent isocitrate dehydrogenase wild type glioblastoma. We explore w... Read More about Neurosurgical application of olaparib from a thermo-responsive paste potentiates DNA damage to prolong survival in malignant glioma.

Tumour Heterogeneity and Disease Infiltration as Paradigms of Glioblastoma Treatment Resistance (2024)
Journal Article
Malhotra, P., & Rahman, R. (2024). Tumour Heterogeneity and Disease Infiltration as Paradigms of Glioblastoma Treatment Resistance. Onco, 4(4), 349-358. https://doi.org/10.3390/onco4040024

Isocitrate dehydrogenase wild-type glioblastoma, a Grade 4 malignant brain neoplasm, remains resistant to multimodal treatment, with a median survival of 16 months from diagnosis with no geographical bias. Despite increasing appreciation of intra-tum... Read More about Tumour Heterogeneity and Disease Infiltration as Paradigms of Glioblastoma Treatment Resistance.

Supramolecular hydrogels enable co-delivery of chemotherapeutics with synergistic efficacy against patient-derived glioblastoma cells and spheroids (2024)
Journal Article
Cavanagh, R. J., Baquain, S., Alexander, C., Scherman, O. A., & Rahman, R. (2024). Supramolecular hydrogels enable co-delivery of chemotherapeutics with synergistic efficacy against patient-derived glioblastoma cells and spheroids. RSC Advances, https://doi.org/10.1039/D4PM00177J

Drug combinations have been shown to be highly effective in many cancer therapies but the ratios of the individual drugs must be adjusted carefully and formulated appropriately to ensure synergistic action. Here we assessed combinations of doxorubici... Read More about Supramolecular hydrogels enable co-delivery of chemotherapeutics with synergistic efficacy against patient-derived glioblastoma cells and spheroids.

Radiogenomics as an Integrated Approach to Glioblastoma Precision Medicine (2024)
Journal Article
Sanchez, I., & Rahman, R. (2024). Radiogenomics as an Integrated Approach to Glioblastoma Precision Medicine. Current Oncology Reports, https://doi.org/10.1007/s11912-024-01580-z

Purpose of Review
Isocitrate dehydrogenase wild-type glioblastoma is the most aggressive primary brain tumour in adults. Its infiltrative nature and heterogeneity confer a dismal prognosis, despite multimodal treatment. Precision medicine is increa... Read More about Radiogenomics as an Integrated Approach to Glioblastoma Precision Medicine.

Free drug and ROS-responsive nanoparticle delivery of synergistic doxorubicin and olaparib combinations to triple negative breast cancer models (2024)
Journal Article
Cavanagh, R. J., Monteiro, P. F., Moloney, C., Travanut, A., Mehradnia, F., Taresco, V., …Alexander, C. (2024). Free drug and ROS-responsive nanoparticle delivery of synergistic doxorubicin and olaparib combinations to triple negative breast cancer models. Biomaterials Science, 12(7), 1822-1840. https://doi.org/10.1039/d3bm01931d

Combinations of the topoisomerase II inhibitor doxorubicin and the poly (ADP-ribose) polymerase inhibitor olaparib offer potential drug-drug synergy for the treatment of triple negative breast cancers (TNBC). In this study we performed in vitro scree... Read More about Free drug and ROS-responsive nanoparticle delivery of synergistic doxorubicin and olaparib combinations to triple negative breast cancer models.

Wireless electrical–molecular quantum signalling for cancer cell apoptosis (2023)
Journal Article
Jain, A., Gosling, J., Liu, S., Wang, H., Stone, E. M., Chakraborty, S., …Rawson, F. J. (2024). Wireless electrical–molecular quantum signalling for cancer cell apoptosis. Nature Nanotechnology, 19, 106-114. https://doi.org/10.1038/s41565-023-01496-y

Quantum biological tunnelling for electron transfer is involved in controlling essential functions for life such as cellular respiration and homoeostasis. Understanding and controlling the quantum effects in biology has the potential to modulate biol... Read More about Wireless electrical–molecular quantum signalling for cancer cell apoptosis.

Chain-extension in hyperbranched polymers alters tissue distribution and cytotoxicity profiles in orthotopic models of triple negative breast cancers (2023)
Journal Article
Moloney, C., Mehradnia, F., Cavanagh, R. J., Ibrahim, A., Pearce, A. K., Ritchie, A. A., …Alexander, C. (2023). Chain-extension in hyperbranched polymers alters tissue distribution and cytotoxicity profiles in orthotopic models of triple negative breast cancers. Biomaterials Science, 11, 6545-6560. https://doi.org/10.1039/d3bm00609c

The therapeutic efficacy of nanomedicines is highly dependent on their access to target sites in the body, and this in turn is markedly affected by their size, shape and transport properties in tissue. Although there have been many studies in this ar... Read More about Chain-extension in hyperbranched polymers alters tissue distribution and cytotoxicity profiles in orthotopic models of triple negative breast cancers.

Spatially resolved transcriptomic profiles reveal unique defining molecular features of infiltrative 5ALA-metabolizing cells associated with glioblastoma recurrence (2023)
Journal Article
Andrieux, G., Das, T., Griffin, M., Straehle, J., Paine, S. M., Beck, J., …Chakraborty, S. (2023). Spatially resolved transcriptomic profiles reveal unique defining molecular features of infiltrative 5ALA-metabolizing cells associated with glioblastoma recurrence. Genome Medicine, 15, Article 48. https://doi.org/10.1186/s13073-023-01207-1

Background

Spatiotemporal heterogeneity originating from genomic and transcriptional variation was found to contribute to subtype switching in isocitrate dehydrogenase-1 wild-type glioblastoma (GBM) prior to and upon recurrence. Fluorescence-guide... Read More about Spatially resolved transcriptomic profiles reveal unique defining molecular features of infiltrative 5ALA-metabolizing cells associated with glioblastoma recurrence.

Untargeted Metabolomic Characterization of Glioblastoma Intra-Tumor Heterogeneity Using OrbiSIMS (2023)
Journal Article
He, W., Edney, M. K., Paine, S. M. L., Griffiths, R. L., Scurr, D. J., Rahman, R., & Kim, D.-H. (2023). Untargeted Metabolomic Characterization of Glioblastoma Intra-Tumor Heterogeneity Using OrbiSIMS. Analytical Chemistry, 95(14), 5994-6001. https://doi.org/10.1021/acs.analchem.2c05807

Glioblastoma (GBM) is an incurable brain cancer with a median survival of less than two years from diagnosis. The standard treatment of GBM is multimodality therapy comprising surgical resection, radiation, and chemotherapy. However, prognosis remain... Read More about Untargeted Metabolomic Characterization of Glioblastoma Intra-Tumor Heterogeneity Using OrbiSIMS.

Evaluation of cannabidiol nanoparticles and nanoemulsion biodistribution in the central nervous system after intrathecal administration for the treatment of pain (2023)
Journal Article
Muresan, P., Woodhams, S., Smith, F., Taresco, V., Shah, J., Wong, M., …Marlow, M. (2023). Evaluation of cannabidiol nanoparticles and nanoemulsion biodistribution in the central nervous system after intrathecal administration for the treatment of pain. Nanomedicine: Nanotechnology, Biology and Medicine, 49, Article 102664. https://doi.org/10.1016/j.nano.2023.102664

We investigated how the biodistribution of cannabidiol (CBD) within the central nervous system (CNS) is influenced by two different formulations, an oil-in-water (O/W) nanoemulsion and polymer-coated nanoparticles (PCNPs). We observed that both CBD f... Read More about Evaluation of cannabidiol nanoparticles and nanoemulsion biodistribution in the central nervous system after intrathecal administration for the treatment of pain.

Stimuli-Responsive Multifunctional Nanomedicine for Enhanced Glioblastoma Chemotherapy Augments Multistage Blood-to-Brain Trafficking and Tumor Targeting (2023)
Journal Article
Martins, C., Araújo, M., Malfanti, A., Pacheco, C., Smith, S. J., Ucakar, B., …Sarmento, B. (in press). Stimuli-Responsive Multifunctional Nanomedicine for Enhanced Glioblastoma Chemotherapy Augments Multistage Blood-to-Brain Trafficking and Tumor Targeting. Small, Article 2300029. https://doi.org/10.1002/smll.202300029

Minimal therapeutic advances have been achieved over the past two decades for glioblastoma (GBM), which remains an unmet clinical need. Here, hypothesis-driven stimuli-responsive nanoparticles (NPs) for docetaxel (DTX) delivery to GBM are reported, w... Read More about Stimuli-Responsive Multifunctional Nanomedicine for Enhanced Glioblastoma Chemotherapy Augments Multistage Blood-to-Brain Trafficking and Tumor Targeting.

Low-Density Lipoprotein Pathway Is a Ubiquitous Metabolic Vulnerability in High Grade Glioma Amenable for Nanotherapeutic Delivery (2023)
Journal Article
Adekeye, A. O., Needham, D., & Rahman, R. (2023). Low-Density Lipoprotein Pathway Is a Ubiquitous Metabolic Vulnerability in High Grade Glioma Amenable for Nanotherapeutic Delivery. Pharmaceutics, 15(2), Article 599. https://doi.org/10.3390/pharmaceutics15020599

Metabolic reprogramming, through increased uptake of cholesterol in the form of low-density lipoproteins (LDL), is one way by which cancer cells, including high grade gliomas (HGG), maintain their rapid growth. In this study, we determined LDL recept... Read More about Low-Density Lipoprotein Pathway Is a Ubiquitous Metabolic Vulnerability in High Grade Glioma Amenable for Nanotherapeutic Delivery.

Childhood Brain Tumors: A Review of Strategies to Translate CNS Drug Delivery to Clinical Trials (2023)
Journal Article
Rahman, R., Janowski, M., Killick-Cole, C. L., Singleton, W. G. B., Campbell, E., Walczak, P., …Walker, D. A. (2023). Childhood Brain Tumors: A Review of Strategies to Translate CNS Drug Delivery to Clinical Trials. Cancers, 15(3), Article 857. https://doi.org/10.3390/cancers15030857

Brain and spinal tumors affect 1 in 1000 people by 25 years of age, and have diverse histological, biological, anatomical and dissemination characteristics. A mortality of 30–40% means the majority are cured, although two-thirds have life-long disabi... Read More about Childhood Brain Tumors: A Review of Strategies to Translate CNS Drug Delivery to Clinical Trials.

Development of nanoparticle loaded microneedles for drug delivery to a brain tumour resection site (2022)
Journal Article
Muresan, P., McCrorie, P., Smith, F., Vasey, C., Taresco, V., Scurr, D. J., …Marlow, M. (2023). Development of nanoparticle loaded microneedles for drug delivery to a brain tumour resection site. European Journal of Pharmaceutics and Biopharmaceutics, 182, 53-61. https://doi.org/10.1016/j.ejpb.2022.11.016

Systemic drug delivery to the central nervous system (CNS) has been historically impeded by the presence of the blood brain barrier rendering many therapies inefficacious to any cancer cells residing within the brain. Therefore, local drug delivery s... Read More about Development of nanoparticle loaded microneedles for drug delivery to a brain tumour resection site.

Histopathological impact of Redox-responsive methacrylamide based micellar nanoparticles on Orthotopic Models of Triple Negative Breast Cancers (2022)
Journal Article
Mehradnia, F., Moloney, C., Cavanagh, R., Pearce, A. K., Ritchie, A., Clarke, P., …Alexander, C. (2022). Histopathological impact of Redox-responsive methacrylamide based micellar nanoparticles on Orthotopic Models of Triple Negative Breast Cancers. British Journal of Pharmacy, 7(2), https://doi.org/10.5920/bjpharm.1173

The therapeutic efficacy of anticancer nanocarriers ishighly dependent on their size, shape, targeting ability, and stimuli-responsiveness. Herein, we studied the in vivo therapeutic efficacy ofDoxorubicin (Dox) loaded redox responsive micellar-like... Read More about Histopathological impact of Redox-responsive methacrylamide based micellar nanoparticles on Orthotopic Models of Triple Negative Breast Cancers.

Electric field responsive nanotransducers for glioblastoma (2022)
Journal Article
Jain, A., Jobson, I., Griffin, M., Rahman, R., Smith, S., & Rawson, F. J. (2022). Electric field responsive nanotransducers for glioblastoma. Bioelectronic Medicine, 8(1), Article 17. https://doi.org/10.1186/s42234-022-00099-7

Background

Electric field therapies such as Tumor Treating Fields (TTFields) have emerged as a bioelectronic treatment for isocitrate dehydrogenase wild-type and IDH mutant grade 4 astrocytoma Glioblastoma (GBM). TTFields rely on alternating curre... Read More about Electric field responsive nanotransducers for glioblastoma.

Lipoprotein Deprivation Reveals a Cholesterol-Dependent Therapeutic Vulnerability in Diffuse Glioma Metabolism (2022)
Journal Article
Wood, J., Abdelrazig, S., Evseev, S., Ortori, C., Castellanos-Uribe, M., May, S. T., …Rahman, R. (2022). Lipoprotein Deprivation Reveals a Cholesterol-Dependent Therapeutic Vulnerability in Diffuse Glioma Metabolism. Cancers, 14(16), Article 3873. https://doi.org/10.3390/cancers14163873

Poor outcomes associated with diffuse high-grade gliomas occur in both adults and children, despite substantial progress made in the molecular characterisation of the disease. Targeting the metabolic requirements of cancer cells represents an alterna... Read More about Lipoprotein Deprivation Reveals a Cholesterol-Dependent Therapeutic Vulnerability in Diffuse Glioma Metabolism.

Metabolic modeling-based drug repurposing in Glioblastoma (2022)
Journal Article
Tomi-Andrino, C., Pandele, A., Winzer, K., King, J., Rahman, R., & Kim, D.-H. (2022). Metabolic modeling-based drug repurposing in Glioblastoma. Scientific Reports, 12, Article 11189. https://doi.org/10.1038/s41598-022-14721-w

The manifestation of intra- and inter-tumor heterogeneity hinders the development of ubiquitous cancer treatments, thus requiring a tailored therapy for each cancer type. Specifically, the reprogramming of cellular metabolism has been identified as a... Read More about Metabolic modeling-based drug repurposing in Glioblastoma.

EPCT-03. Working together to accelerate the preclinical to clinical translation of drug delivery systems for children’s brain tumours (2022)
Presentation / Conference Contribution
Campbell, E., Aquilina, K., Dandapani, M., Walker, D., & Rahman, R. (2022). EPCT-03. Working together to accelerate the preclinical to clinical translation of drug delivery systems for children’s brain tumours. Neuro-Oncology, 24(Supplement 1), i36-i36. https://doi.org/10.1093/neuonc/noac079.131

Children's brain tumours are the biggest cancer killer in children and young adults. Several techniques, such as intra-cerebrospinal fluid chemotherapy, ultrasound-mediated blood-brain barrier disruption, convection enhanced delivery, polymer deliver... Read More about EPCT-03. Working together to accelerate the preclinical to clinical translation of drug delivery systems for children’s brain tumours.

Detection of Label-Free Drugs within Brain Tissue Using Orbitrap Secondary Ion Mass Spectrometry as a Complement to Neuro-Oncological Drug Delivery (2022)
Journal Article
McCrorie, P., Rowlinson, J., Scurr, D. J., Marlow, M., & Rahman, R. (2022). Detection of Label-Free Drugs within Brain Tissue Using Orbitrap Secondary Ion Mass Spectrometry as a Complement to Neuro-Oncological Drug Delivery. Pharmaceutics, 14(3), Article 571. https://doi.org/10.3390/pharmaceutics14030571

Historically, pre-clinical neuro-oncological drug delivery studies have exhaustively relied upon overall animal survival as an exclusive measure of efficacy. However, with no adopted methodology to both image and quantitate brain parenchyma penetrati... Read More about Detection of Label-Free Drugs within Brain Tissue Using Orbitrap Secondary Ion Mass Spectrometry as a Complement to Neuro-Oncological Drug Delivery.