Nanoparticle-mediated convection-enhanced delivery of a DNA intercalator to gliomas circumvents temozolomide resistance

Wang, Yongheng; Jiang, Yuhang; Wei, Dengshuai; Singh, Prati Pal; Yu, Yingjie; Lee, Teresa; Zhang, Lingpu; Mandl, Hanna K.; Piotrowski-Daspit, Alexandra S.; Chen, Xinyuan; Li, Fan; Li, Xing; Cheng, Yiyu; Josowitz, Alexander; Yang, Fan; Zhao, Yao; Wang, Fuyi; Zhao, Zhenwen; Hüttner, Anita; Bindra, Ranjit S.; Xiao, Haihua; Saltzman, W. Mark

doi:10.1038/s41551-021-00728-7

Cited by 118 publications

(81 citation statements)

References 66 publications

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“…1 D). Abplatin (IV) was believed to be reduced by intracellular reducing agents such as glutathione (GSH) and ascorbic acid to release Pt(II) for DNA binding [ 15 , 16 , 30 ]. The results showed that within 12 h, 80%, 10% and 8% of Pt drugs were released in sodium ascorbate (NaVc) aqueous solution, acetate buffer solution, and PBS, respectively, indicating Pt drugs could be rapidly released under the reductive environment (Fig.…”

Section: Resultsmentioning

confidence: 99%

Abplatin(IV) inhibited tumor growth on a patient derived cancer model of hepatocellular carcinoma and its comparative multi-omics study with cisplatin

Zhang

et al. 2022

J Nanobiotechnol

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Background Cisplatin, the alkylating agent of platinum(II) (Pt(II)), is the most common antitumor drug in clinic; however, it has many side effects, therefore it is higly desired to develop low toxicity platinum(IV) (Pt(IV)) drugs. Multi-omics analysis, as a powerful tool, has been frequently employed for the mechanism study of a certain therapy at the molecular level, which might be helpful for elucidating the mechanism of platinum drugs and facilitating their clinical application. Methods Strating form cisplatin, a hydrophobic Pt(IV) prodrug (CisPt(IV)) with two hydrophobic aliphatic chains was synthesized, and further encapsulated with a drug carrier, human serum albumin (HSA), to form nanoparticles, namely AbPlatin(IV). The anticancer effect of AbPlatin(IV) was investigated in vitro and in vivo. Moreover, transcriptomics, metabolomics and lipidomics were performed to explore the mechanism of AbPlatin(IV). Results Compared with cisplatin, Abplatin(IV) exhibited better tumor-targeting effect and greater tumor inhibition rate. Lipidomics study showed that Abplatin(IV) might induce the changes of BEL-7404 cell membrane, and cause the disorder of glycerophospholipids and sphingolipids. In addition, transcriptomics and metabolomics study showed that Abplatin(IV) significantly disturbed the purine metabolism pathway. Conclusions This research highlighted the development of Abplatin(IV) and the use of multi-omics for the mechanism elucidation of prodrug, which is the key to the clinical translation of prodrug. Graphical Abstract

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Section: Resultsmentioning

confidence: 99%

Abplatin(IV) inhibited tumor growth on a patient derived cancer model of hepatocellular carcinoma and its comparative multi-omics study with cisplatin

Zhang

et al. 2022

J Nanobiotechnol

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“…Based on the mechanisms used to induce ER stress, ICD inducers are divided into two categories: Type I inducers, such as mitoxantrone and cyclophosphamide, target cytosolic proteins or DNA-replication proteins rather than targeting the ER directly and induce ER stress through secondary or collateral effects; Type II inducers selectively target the ER and disturb ER homeostasis. Moreover, the coexistence of ROS and ER stress can significantly increase the secretion of DAMPs (Krysko et al., 2012 ; Wang et al., 2021 ), which is why ICD was more significant in the SDT group. However, in our study, ER stress occurred not only in the SDT group but also in the IRO@FA group, and IRO@FA NPs alone also induced ICD.…”

Section: Discussionmentioning

confidence: 99%

Sonosensitizer nanoplatform-mediated sonodynamic therapy induced immunogenic cell death and tumor immune microenvironment variation

et al. 2022

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Epithelial ovarian cancer (EOC) is one of the most lethal gynecologic malignancies, and effective treatments are still lacking due to drug tolerance and tumor recurrence. In this study, we aimed to investigate the effects of sonodynamic therapy (SDT) on ovarian cancer and its potential mechanism. Folate receptor-targeted and ultrasound-responsive nanoparticles (NPs) were constructed using PLGA-PEG-FA (PLGA: poly (lactic-co-glycolic) acid, polyethylene glycol (PEG), FA: folate), the reactive oxygen species (ROS)-generating sonosensitizer IR780 and the oxygen-carrying material perfluorohexane (PFH), termed IRO@FA NPs. The antitumor effect of NPs triggered by ultrasound (US) was measured by an apoptosis assay in a C57/BL6 mouse model. Immunochemistry and flow cytometry were used to detect the proportion of CD3 + T, CD4 + T, CD8 + T cells and activated dendritic cells (DCs) in spleens and tumor tissues to assess variation in the immune response. Moreover, endoplasmic reticulum (ER) stress and immunogenic cell death (ICD) markers (high mobility group protein box-1, ATP and calreticulin) were detected to identify potential mechanisms. The results showed that IRO@FA NP-mediated SDT promoted ID8 cell apoptosis both in vitro and in vivo. The densities of CD3 + and CD8 + T lymphocytes and inflammatory markers were upregulated in tumor tissues. IRO@FA NP-mediated SDT prompted DC maturation and T lymphocyte infiltration by inducing ID8 cell ICD.

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“…[25,26] For instance, one of the approaches is convection-enhanced delivery (CED), which is an efficient technology that circumvents the BBB by means of catheters connected to an infusion pump and inserted into the brain's interstitial spaces. [27] The mechanism behind CED is bulk flow, which is based on a concentration gradient and follows Fick's law "J = −D∇C," where D represents tissue diffusivity and ∇C denotes the concentration gradient. Furthermore, the molar flow is proportional to the concentration gradient multiplied by a tissue diffusivity coefficient.…”

Section: Invasive Methodsmentioning

confidence: 99%

Intranasal Delivery of Functionalized Polymeric Nanomaterials to the Brain

Zha

Wong

All

2022

Adv Healthcare Materials

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Intravenous delivery of nanomaterials containing therapeutic agents and various cargos for treating neurological disorders is often constrained by low delivery efficacy due to difficulties in passing the blood-brain barrier (BBB). Nanoparticles (NPs) administered intranasally can move along olfactory and trigeminal nerves so that they do not need to pass through the BBB, allowing non-invasive, direct access to selective neural pathways within the brain. Hence, intranasal (IN) administration of NPs can effectively deliver drugs and genes into targeted regions of the brain, holding potential for efficacious disease treatment in the central nervous system (CNS). In this review, current methods for delivering conjugated NPs to the brain are primarily discussed. Distinctive potential mechanisms of therapeutic nanocomposites delivered via IN pathways to the brain are then discussed. Recent progress in developing functional NPs for applications in multimodal bioimaging, drug delivery, diagnostics, and therapeutics is also reviewed. This review is then concluded by discussing existing challenges, new directions, and future perspectives in IN delivery of nanomaterials.

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Nanoparticle-mediated convection-enhanced delivery of a DNA intercalator to gliomas circumvents temozolomide resistance

Cited by 118 publications

References 66 publications

Abplatin(IV) inhibited tumor growth on a patient derived cancer model of hepatocellular carcinoma and its comparative multi-omics study with cisplatin

Abplatin(IV) inhibited tumor growth on a patient derived cancer model of hepatocellular carcinoma and its comparative multi-omics study with cisplatin

Sonosensitizer nanoplatform-mediated sonodynamic therapy induced immunogenic cell death and tumor immune microenvironment variation

Intranasal Delivery of Functionalized Polymeric Nanomaterials to the Brain

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