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    Local delivery to malignant brain tumors: potential biomaterial-based therapeutic/adjuvant strategies
    (Cambridge : RSC, 2021) Alghamdi, Majed; Gumbleton, Mark; Newland, Ben
    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 possible), plus irradiation and adjuvant chemotherapy. Despite treatment, the prognosis is still poor, and the tumor often recurs within two centimeters of the original tumor. A promising approach to improving the efficacy of GBM therapeutics is to utilize biomaterials to deliver them locally at the tumor site. Local delivery to GBM offers several advantages over systemic administration, such as bypassing the blood-brain barrier and increasing the bioavailability of the therapeutic at the tumor site without causing systemic toxicity. Local delivery may also combat tumor recurrence by maintaining sufficient drug concentrations at and surrounding the original tumor area. Herein, we critically appraised the literature on local delivery systems based within the following categories: polymer-based implantable devices, polymeric injectable systems, and hydrogel drug delivery systems. We also discussed the negative effect of hypoxia on treatment strategies and how one might utilize local implantation of oxygen-generating biomaterials as an adjuvant to enhance current therapeutic strategies. © 2021 The Royal Society of Chemistry.
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    Mechanochemical activation of disulfide-based multifunctional polymers for theranostic drug release
    (Cambridge : RSC, 2021) Shi, Zhiyuan; Song, Qingchuan; Göstl, Robert; Herrmann, Andreas
    Drug delivery systems responsive to physicochemical stimuli allow spatiotemporal control over drug activity to overcome limitations of systemic drug administration. Alongside, the non-invasive real-time tracking of drug release and uptake remains challenging as pharmacophore and reporter function are rarely unified within one molecule. Here, we present an ultrasound-responsive release system based on the mechanochemically induced 5-exo-trigcyclization upon scission of disulfides bearing cargo molecules attachedviaβ-carbonate linker within the center of a water soluble polymer. In this bifunctional theranostic approach, we release one reporter molecule per drug molecule to quantitatively track drug release and distribution within the cell in real-time. We useN-butyl-4-hydroxy-1,8-naphthalimide and umbelliferone as fluorescent reporter molecules to accompany the release of camptothecin and gemcitabine as clinically employed anticancer agents. The generality of this approach paves the way for the theranostic release of a variety of probes and drugs by ultrasound. © The Royal Society of Chemistry 2020.
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    Sonopharmacology: controlling pharmacotherapy and diagnosis by ultrasound-induced polymer mechanochemistry
    (Cambridge : RSC, 2022) Yildiz, Deniz; Göstl, Robert; Herrmann, Andreas
    Active pharmaceutical ingredients are the most consequential and widely employed treatment in medicine although they suffer from many systematic limitations, particularly off-target activity and toxicity. To mitigate these effects, stimuli-responsive controlled delivery and release strategies for drugs are being developed. Fueled by the field of polymer mechanochemistry, recently new molecular technologies enabled the emergence of force as an unprecedented stimulus for this purpose by using ultrasound. In this research area, termed sonopharmacology, mechanophores bearing drug molecules are incorporated within biocompatible macromolecular scaffolds as preprogrammed, latent moieties. This review presents the novelties in controlling drug activation, monitoring, and release by ultrasound, while discussing the limitations and challenges for future developments.
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    Correction: Mechanochemical activation of disulfide-based multifunctional polymers for theranostic drug release
    (Cambridge : RSC, 2021) Shi, Zhiyuan; Song, Qingchuan; Göstl, Robert; Herrmann, Andreas
    Correction for ‘Mechanochemical activation of disulfide-based multifunctional polymers for theranostic drug release’ by Zhiyuan Shi et al., Chem. Sci., 2021, 12, 1668–1674, DOI: 10.1039/D0SC06054B.