Revisiting Platinum-Based Anticancer Drugs to Overcome Gliomas

Jeon, Jaewan; Lee, Sung-Min; Kim, Hyun Woo; Kang, Hyunkoo; Youn, HyeSook; Jo, Sunmi; Youn, BuHyun; Kim, Hae Yu

doi:10.3390/ijms22105111

Cited by 23 publications

(16 citation statements)

References 218 publications

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“…Therefore, the restricted intranasal delivery of Pt-based drugs can be anticipated in the treatment of GB. To date, few studies have reported to evaluate the in vivo performance of Pt-based agents against GB, although their significance has been recognized to repurpose or reposition the existing chemotherapeutic drugs for GB treatment [ 56 , 57 ]. In the sparse reports, only two cases administered the Pt agents via IN route, all about nanoformulations based on either carboplatin or FePt alloy nanoparticles [ 58 , 59 ].…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Validation of a Bioinspired Catechol-Functionalized Pt(IV) Prodrug for Preclinical Intranasal Glioblastoma Treatment

Mao

Calero-Pérez

et al. 2022

Cancers

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Glioblastoma is the most malignant and frequently occurring type of brain tumors in adults. Its treatment has been greatly hampered by the difficulty to achieve effective therapeutic concentration in the tumor sites due to its location and the blood–brain barrier. Intranasal administration has emerged as an alternative for drug delivery into the brain though mucopenetration, and rapid mucociliary clearance still remains an issue to be solved before its implementation. To address these issues, based on the intriguing properties of proteins secreted by mussels, polyphenol and catechol functionalization has already been used to promote mucopenetration, intranasal delivery and transport across the blood–brain barrier. Thus, herein we report the synthesis and study of complex 1, a Pt(IV) prodrug functionalized with catecholic moieties. This complex considerably augmented solubility in contrast to cisplatin and showed a comparable cytotoxic effect on cisplatin in HeLa, 1Br3G and GL261 cells. Furthermore, preclinical in vivo therapy using the intranasal administration route suggested that it can reach the brain and inhibit the growth of orthotopic GL261 glioblastoma. These results open new opportunities for catechol-bearing anticancer prodrugs in the treatment for brain tumors via intranasal administration.

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Section: Resultsmentioning

confidence: 99%

Synthesis and Validation of a Bioinspired Catechol-Functionalized Pt(IV) Prodrug for Preclinical Intranasal Glioblastoma Treatment

Mao

Calero-Pérez

et al. 2022

Cancers

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“…Platinum application as an anticancer agent is widely known, especially due to cis-platinum and its derivatives. The usefulness of complexed platinum drugs is severely limited by serious systemic toxicity that is induced in a dose-dependent manner [ 1 ]. The development of new nanoplatforms, which could modify the biological disposition of Pt compounds, reduce its toxicity and perhaps attenuate the undesirable side effects, is one of the most challenging tasks in experimental oncology to date [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Oxidative Status as an Attribute for Selective Antitumor Activity of Platinum-Containing Nanoparticles against Hepatocellular Carcinoma

Wawrowicz

Majkowska-Pilip

Szwed

et al. 2022

IJMS

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Overcoming the limitations for efficient and selective drug delivery is one of the most challenging obstacles for newly designed anticancer agents. In this study, we present two types of platinum-based nanoparticles (NP), ultrasmall 2 nm PtNPs and core-shell 30 nm Au@Pt, which can be highly cytotoxic in an oxidative environment and remain biologically inactive in cells with lower oxidative status. Our research highlighted the differences in platinum nanoparticle-induced chemotoxicity and is the first study examining its mechanism as a substantial aspect of Au@Pt/PtNPs biological activity. Selectively induced oxidative stress was found to be a primary trigger of NPs’ toxicity. Significant differences between Au@Pt and PtNPs were observed especially during 24 h treatment, due to successful intranuclear PtNPs location (~13% of internalized fraction). Reactive oxygen species (ROS)-level induced from both NPs types were similar, while reduction of reduced glutathione (GSH) intracellular content was stronger after treatment with PtNPs. Any biological activity was found in HER2+ breast cancer cells, which have only slightly increased oxidative status. Platinum-containing nanoparticles are an interesting tool for the improvement of selectivity in anticancer therapies against hepatocellular carcinoma (HCC). Due to intranuclear uptake, 2 nm PtNPs seems to be more promising for further research for HCC therapy.

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“…Accordingly, the majority of patients with GBM experience tumor recurrence, and recurrent tumors commonly show a poor response to standard therapy [ 6 ]. Despite advancements in the understanding of GBM molecular diagnosis and ongoing trials on targeted therapies, standard therapy has not advanced over the past two decades [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Targeting Glioblastoma Stem Cells to Overcome Chemoresistance: An Overview of Current Therapeutic Strategies

et al. 2022

Self Cite

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Glioblastoma (GBM) is the most malignant primary brain tumor. The current standard approach in GBM is surgery, followed by treatment with radiation and temozolomide (TMZ); however, GBM is highly resistant to current therapies, and the standard of care has not been revised over the last two decades, indicating an unmet need for new therapies. GBM stem cells (GSCs) are a major cause of chemoresistance due to their ability to confer heterogeneity and tumorigenic capacity. To improve patient outcomes and survival, it is necessary to understand the properties and mechanisms underlying GSC chemoresistance. In this review, we describe the current knowledge on various resistance mechanisms of GBM to therapeutic agents, with a special focus on TMZ, and summarize the recent findings on the intrinsic and extrinsic mechanisms of chemoresistance in GSCs. We also discuss novel therapeutic strategies, including molecular targeting, autophagy inhibition, oncolytic viral therapy, drug repositioning, and targeting of GSC niches, to eliminate GSCs, from basic research findings to ongoing clinical trials. Although the development of effective therapies for GBM is still challenging, this review provides a better understanding of GSCs and offers future directions for successful GBM therapy.

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Revisiting Platinum-Based Anticancer Drugs to Overcome Gliomas

Cited by 23 publications

References 218 publications

Synthesis and Validation of a Bioinspired Catechol-Functionalized Pt(IV) Prodrug for Preclinical Intranasal Glioblastoma Treatment

Synthesis and Validation of a Bioinspired Catechol-Functionalized Pt(IV) Prodrug for Preclinical Intranasal Glioblastoma Treatment

Oxidative Status as an Attribute for Selective Antitumor Activity of Platinum-Containing Nanoparticles against Hepatocellular Carcinoma

Targeting Glioblastoma Stem Cells to Overcome Chemoresistance: An Overview of Current Therapeutic Strategies

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