Local delivery to malignant brain tumors: potential biomaterial-based therapeutic/adjuvant strategies

Alghamdi, Majed; Gumbleton, Mark; Newland, Ben

doi:10.1039/d1bm00896j

Cited by 19 publications

(17 citation statements)

References 145 publications

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“…Analysis of the hydrogel sizes indicated that they swelled by approximately 112% of their original template size once removed from the template (Figure 3f). Local drug delivery as a strategy for therapeutic delivery to brain cancers would allow the administration of drugs that cannot pass the blood-brain barrier [32]. Local delivery therefore vastly increases the range of potential chemotherapeutic drugs that can be utilized.…”

Section: Resultsmentioning

confidence: 99%

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Well-Defined Polyethylene Glycol Microscale Hydrogel Blocks Containing Gold Nanorods for Dual Photothermal and Chemotherapeutic Therapy

et al. 2022

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Local drug delivery offers a means of achieving a high concentration of therapeutic agents directly at the tumor site, whilst minimizing systemic toxicity. For heterogenous cancers such as glioblastoma, multimodal therapeutic approaches hold promise for better efficacy. Herein, we aimed to create a well-defined and reproducible drug delivery system that also incorporates gold nanorods for photothermal therapy. Solvent-assisted micromolding was used to create uniform sacrificial templates in which microscale hydrogels were formed with and without gold nanorods throughout their structure. The microscale hydrogels could be loaded with doxorubicin, releasing it over a period of one week, causing toxicity to glioma cells. Since these microscale hydrogels were designed for direct intratumoral injection, therefore bypassing the blood–brain barrier, the highly potent breast cancer therapeutic doxorubicin was repurposed for use in this study. By contrast, the unloaded hydrogels were well tolerated, without decreasing cell viability. Irradiation with near-infrared light caused heating of the hydrogels, showing that if concentrated at an injection site, these hydrogels maybe able to cause anticancer activity through two separate mechanisms.

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Section: Resultsmentioning

confidence: 99%

“…Local drug delivery as a strategy for therapeutic delivery to brain cancers would allow the administration of drugs that cannot pass the blood–brain barrier [ 32 ]. Local delivery therefore vastly increases the range of potential chemotherapeutic drugs that can be utilized.…”

Section: Resultsmentioning

confidence: 99%

Well-Defined Polyethylene Glycol Microscale Hydrogel Blocks Containing Gold Nanorods for Dual Photothermal and Chemotherapeutic Therapy

et al. 2022

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“…Compared with systemic medication, loading drugs in the internal sustained-release carrier of the implant can enable the slow release of the drugs into the microenvironment around the implant, which can not only reduce drug dosage and complications but also achieve better therapeutic effects [ 48 ]. Based on the above ideas, this study proposed a drug sustained-release system for osteoporosis treatment with Mg-MOF-74 as the drug carrier, and icariin was loaded to obtain ICA@MOF.…”

Section: Discussionmentioning

confidence: 99%

A novel hierarchical biofunctionalized 3D-printed porous Ti6Al4V scaffold with enhanced osteoporotic osseointegration through osteoimmunomodulation

et al. 2022

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Background Femoral stem of titanium alloy has been widely used for hip arthroplasty with considerable efficacy; however, the application of this implant in patients with osteoporosis is limited due to excessive bone resorption. Macrophages participate in the regulation of inflammatory response and have been a topic of increasing research interest in implant field. However, few study has explored the link between macrophage polarization and osteogenic–osteoclastic differentiation. The present study aims to develop a novel hierarchical biofunctionalized 3D-printed porous Ti6Al4V scaffold with enhanced osteoporotic osseointegration through immunotherapy. Method To improve the osteointegration under osteoporosis, we developed a hierarchical biofunctionalized 3D-printed porous Ti6Al4V scaffold (PT). Biomimetic extracellular matrix (ECM) was constructed inside the interconnected pores of PT in micro-scale. And in nano-scale, a drug cargo icariin@Mg-MOF-74 (ICA@MOF) was wrapped in ECM-like structure that can control release of icariin and Mg2+. Results In this novel hierarchical biofunctionalized 3D-printed porous Ti6Al4V scaffold, the macroporous structure provides mechanical support, the microporous structure facilitates cell adhesion and enhances biocompatibility, and the nanostructure plays a biological effect. We also demonstrate the formation of abundant new bone at peripheral and internal sites after intramedullary implantation of the biofunctionalized PT into the distal femur in osteoporotic rats. We further find that the controlled-release of icariin and Mg2+ from the biofunctionalized PT can significantly improve the polarization of M0 macrophages to M2-type by inhibiting notch1 signaling pathway and induce the secretion of anti-inflammatory cytokines; thus, it significantly ameliorates bone metabolism, which contributes to improving the osseointegration between the PT and osteoporotic bone. Conclusion The therapeutic potential of hierarchical PT implants containing controlled release system are effective in geriatric orthopaedic osseointegration. Graphical Abstract

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“…Metastasis occurs within approximately ∼2 cm of the tumor's original site, which means it is close to where the drugs were loaded locally; the administration of the drugs will no longer face the BBB limitations [249]. Different strategies for local delivery to improve the GBM survival rate have been developed, including intranasal drugs delivery, convection enhanced delivery, and direct injection of the drugs including rigid implants and hydrogels [250].…”

Section: Local Deliverymentioning

confidence: 99%

Drug Delivery Systems in the Development of Novel Strategies for Glioblastoma Treatment

et al. 2022

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Glioblastoma multiforme (GBM) is a grade IV glioma considered the most fatal cancer of the central nervous system (CNS), with less than a 5% survival rate after five years. The tumor heterogeneity, the high infiltrative behavior of its cells, and the blood–brain barrier (BBB) that limits the access of therapeutic drugs to the brain are the main reasons hampering the current standard treatment efficiency. Following the tumor resection, the infiltrative remaining GBM cells, which are resistant to chemotherapy and radiotherapy, can further invade the surrounding brain parenchyma. Consequently, the development of new strategies to treat parenchyma-infiltrating GBM cells, such as vaccines, nanotherapies, and tumor cells traps including drug delivery systems, is required. For example, the chemoattractant CXCL12, by binding to its CXCR4 receptor, activates signaling pathways that play a critical role in tumor progression and invasion, making it an interesting therapeutic target to properly control the direction of GBM cell migration for treatment proposes. Moreover, the interstitial fluid flow (IFF) is also implicated in increasing the GBM cell migration through the activation of the CXCL12-CXCR4 signaling pathway. However, due to its complex and variable nature, the influence of the IFF on the efficiency of drug delivery systems is not well understood yet. Therefore, this review discusses novel drug delivery strategies to overcome the GBM treatment limitations, focusing on chemokines such as CXCL12 as an innovative approach to reverse the migration of infiltrated GBM. Furthermore, recent developments regarding in vitro 3D culture systems aiming to mimic the dynamic peritumoral environment for the optimization of new drug delivery technologies are highlighted.

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Local delivery to malignant brain tumors: potential biomaterial-based therapeutic/adjuvant strategies

Abstract: Glioblastoma (GBM) is the most aggressive malignant brain tumor and is associated with a very poor prognosis. The standard treatment for newly diagnosed patients involves total tumor surgical resection (if...

Cited by 19 publications

References 145 publications

Well-Defined Polyethylene Glycol Microscale Hydrogel Blocks Containing Gold Nanorods for Dual Photothermal and Chemotherapeutic Therapy

Well-Defined Polyethylene Glycol Microscale Hydrogel Blocks Containing Gold Nanorods for Dual Photothermal and Chemotherapeutic Therapy

A novel hierarchical biofunctionalized 3D-printed porous Ti6Al4V scaffold with enhanced osteoporotic osseointegration through osteoimmunomodulation

Drug Delivery Systems in the Development of Novel Strategies for Glioblastoma Treatment

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