Article
Chemistry, Multidisciplinary
J. L. Jimenez-Macias, Y. -C. Lee, E. Miller, T. Finkelberg, M. Zdioruk, G. Berger, C. E. Farquhar, M. O. Nowicki, C. -F. Cho, B. I. Fedeles, A. Loas, B. L. Pentelute, S. E. Lawler
Summary: This study demonstrates for the first time that systemic injection of a Pt(IV) complex conjugated to a brain-penetrant macrocyclic peptide can increase platinum levels in the brain and prolong survival in mouse models of GBM, supporting further development of this approach and the use of brain-penetrating macrocyclic peptide conjugates to deliver non-BBB penetrant drugs to the central nervous system.
JOURNAL OF CONTROLLED RELEASE
(2022)
Review
Chemistry, Multidisciplinary
Shunzhe Zheng, Guanting Li, Jianbin Shi, Xinying Liu, Meng Li, Zhonggui He, Chutong Tian, Ken-ichiro Kamei
Summary: Due to the severe dose-dependent toxicity and drug resistance, platinum (Pt)-based chemotherapy has limitations. Pt(IV) prodrug nanotherapeutics have emerged as a promising approach to improve the antitumor performance of Pt drugs. This article summarizes the latest advances in Pt(IV) prodrug nano-therapeutics, including their potential for overcoming biological barriers and their synergistic effects with other therapies.
JOURNAL OF CONTROLLED RELEASE
(2023)
Review
Chemistry, Inorganic & Nuclear
Zoufeng Xu, Zhigang Wang, Zhiqin Deng, Guangyu Zhu
Summary: Platinum-based anticancer drugs have been widely used in clinical practice for over 40 years, with a focus on developing platinum(IV) prodrugs based on traditional platinum(II) anticancer drugs. Recent progress in the field includes synthesizing platinum(IV) prodrugs with new oxidizing reagents, understanding the hydrolysis and stability of platinum(IV) complexes, and exploring reduction processes to achieve controllable intracellular reduction of platinum(IV) prodrugs. This review aims to enhance researchers' understanding of platinum(IV) anticancer prodrugs and inspire new strategies, ideas, and applications in metal-based drugs.
COORDINATION CHEMISTRY REVIEWS
(2021)
Article
Chemistry, Inorganic & Nuclear
Ran Zhang, Yueyue Zhang, Liumei Tang, Yixing Xu, Hao Li, Xueping Jiang, Xiangdong Xin, Zhongzheng Gui
Summary: A series of Pt(IV) prodrugs containing a microtubule inhibitor paclitaxel were synthesized and evaluated for their antitumor activity. One of the prodrugs, named Ptxplatin, effectively entered cancer cells and induced DNA damage, cell cycle arrest, and inhibition of cell migration. Furthermore, Ptxplatin caused mitochondrial dysfunction and triggered endoplasmic reticulum stress, ultimately leading to cancer cell death.
INORGANIC CHEMISTRY FRONTIERS
(2022)
Article
Chemistry, Multidisciplinary
Jiaqi Guo, Weiyi Tan, Hongjian He, Bing Xu
Summary: This study demonstrates that diglycine-activated succinic esters can significantly enhance the cellular uptake of supramolecular assemblies or prodrugs by converting nanofibers into nanoparticles through autohydrolysis. The autohydrolysis of diglycine-activated succinic esters and drug conjugates also restores the efficacy of the drugs. The U-turn conformation of diglycine promotes intramolecular hydrolysis of diglycine-activated succinic esters, providing a nonenzymatic bond cleavage approach for effective intracellular targeting.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Alessandra Barbanente, Valentina Gandin, Chiara Donati, Carmela Ilaria Pierro, Giovanni Natile, Nicola Margiotta
Summary: Platinum-based drugs have been successful in treating solid tumors, but toxicity and resistance limit their outcomes. Natural products, such as 10-HDA found in royal jelly, are being explored as safe and easily available anti-cancer drugs. In this study, the researchers aimed to combine the functionality of 10-HDA with platinum to develop new compounds with potential anti-cancer activity. The synthesized compounds were characterized and tested for their cytotoxicity against human tumor cell lines. The results showed that some of the new compounds exhibited promising activity against specific tumor cell lines.
NEW JOURNAL OF CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Qiyuan Zhou, Shu Chen, Zoufeng Xu, Gongyuan Liu, Shuyuan Zhang, Zhigang Wang, Man-Kit Tse, Shek-Man Yiu, Guangyu Zhu
Summary: This study reports the synthesis of Pt-IV complexes bearing axial pyridines through ligand exchange reactions. It was discovered that these axial pyridines can be quickly released after reduction, indicating their potential as axial leaving groups. Two multitargeted Pt-IV prodrugs containing bioactive pyridinyl ligands, a PARP inhibitor and an EGFR tyrosine kinase inhibitor, were successfully obtained using this method. These conjugates show great potential for overcoming drug resistance, with the latter inhibiting the growth of Pt-resistant tumor in vivo. This research expands the synthetic methods for Pt-IV prodrugs and increases the range of bioactive axial ligands that can be conjugated to a Pt-IV center.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Houzong Yao, Zhigang Wang, Na Wang, Zhiqin Deng, Gongyuan Liu, Jianghong Zhou, Shu Chen, Jiahai Shi, Guangyu Zhu
Summary: This study presents a rational design of a platinum(IV) anticancer prodrug that can bind to erythrocytes, greatly extending its circulatory half-life and enhancing tumor accumulation. The prodrug demonstrates significantly enhanced antitumor activity and reduced side effects compared to carboplatin.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Inorganic & Nuclear
Violet Eng Yee Lee, Zhi Chiaw Lim, Suet Li Chew, Wee Han Ang
Summary: A common challenge in Pt(IV) prodrug design is the limited repertoire of linkers available to connect the Pt(IV) scaffold with the bioactive payload. This study introduces a new class of Pt(IV) prodrugs using masked self-immolative 4-aminobenzyl linkers for controlled and traceless codrug delivery, which proved to be more effective than traditional methods in vitro.
INORGANIC CHEMISTRY
(2021)
Article
Engineering, Biomedical
Xiaohui Xiao, Yupeng Wang, Jieyao Chen, Peng Qin, Peiyao Chen, Dongfang Zhou, Yue Pan
Summary: This study presents a self-targeting nano-assembly strategy based on platinum(IV)-lactose amphiphilic prodrug for synergistic and safe chemoradiotherapy of hepatocellular carcinoma (HCC). The nano-assembly targets HCC cells and releases cisplatin to induce DNA damage and cell apoptosis. Under X-ray irradiation, the assembly enhances the cell-killing effect of radiotherapy.
Review
Pharmacology & Pharmacy
Yu Fang, Huaimin Wang
Summary: In recent years, hundreds of novel small molecular drugs have been studied in clinical trials for various treatments worldwide. However, less than 10% of these drugs are eventually used due to diverse problems. In order to improve efficacy and efficiency, research has focused on the creation of assemblies of peptide-drug conjugates (PDCs) which have shown potential for overcoming complications. This review summarizes the recent developments in the creation of self-assembled nanostructures of PDCs for cancer therapy and discusses the chemical and physical properties of these drugs and peptides, as well as their mechanisms of action and remaining challenges in this field.
Review
Pharmacology & Pharmacy
Seong-Bin Yang, Nipa Banik, Bomin Han, Dong-Nyeong Lee, Jooho Park
Summary: With advancements in bioinformatics, amino acid-based drug-design strategies have become increasingly important in pharmaceutics. Despite previous limitations of low selectivity and rapid degradation, peptide-based therapeutics combined with drug-delivery systems have emerged, particularly in anticancer therapy.
Article
Chemistry, Multidisciplinary
Dachuan Qi, Lei Xing, Lijun Shen, Wenshuang Sun, Cheng Cai, Chunhua Xue, Xuwei Song, Hua Yu, Hulin Jiang, Chengjun Li, Qingri Jin, Zhiqi Zhang
Summary: This study developed a GSH-depleted drug for breast cancer, which can effectively treat breast cancer by increasing oxidative stress and inducing ferroptosis.
CHINESE CHEMICAL LETTERS
(2022)
Article
Medicine, Research & Experimental
Tushar Date, Kaushik Kuche, Rohan Ghadi, Pradeep Kumar, Sanyog Jain
Summary: Cisplatin is an anticancer drug with challenges in drug delivery. Cisplatin(IV) prodrug formation can effectively resolve these challenges. The selection of axial ligands plays a key role in determining the therapeutic outcomes. Rational design of cisplatin(IV) derivatives can improve their stability and cellular uptake, reducing side effects and offering potential in resolving cisplatin drug delivery challenges.
MOLECULAR PHARMACEUTICS
(2022)
Article
Pharmacology & Pharmacy
Theresa Mendrina, Isabella Poetsch, Hemma Schueffl, Dina Baier, Christine Pirker, Alexander Ries, Bernhard K. K. Keppler, Christian R. R. Kowol, Dan Gibson, Michael Grusch, Walter Berger, Petra Heffeter
Summary: Platinum compounds are effective treatment options for various cancer types, but their use is limited by side effects and drug resistance. A new multi-targeted platinum(IV) prodrug, cisPt(PhB)(2), has shown promising anticancer activity and the ability to overcome drug resistance mechanisms. The drug's mode of action is influenced by cellular fatty acid metabolism and mitochondrial activity. Specifically, it is more effective against cisplatin-resistant cancer cells with Warburg-like properties. This orally applicable prodrug has the potential to improve cancer treatment outcomes.
Review
Clinical Neurology
Niklas von Spreckelsen, Christoph Kesseler, Benjamin Brokinkel, Roland Goldbrunner, Arie Perry, Christian Mawrin
Summary: Invasion of brain tissue by meningiomas is a key factor for their recurrence, but specific treatment approaches targeting the invasive process are not established. This article compiles current knowledge about mechanisms supporting brain tissue invasion by meningiomas and summarizes preclinical models studying targeted therapies with potential inhibitory effects.
Letter
Neuroimaging
Feng Zheng, Niklas von Spreckelsen, Weipeng Hu
JOURNAL OF NEUROINTERVENTIONAL SURGERY
(2023)
Article
Oncology
Choi-Fong Cho, Charlotte E. Farquhar, Colin M. Fadzen, Benjamin Scott, Pei Zhuang, Niklas von Spreckelsen, Andrei Loas, Nina Hartrampf, Bradley L. Pentelute, Sean E. Lawler
Summary: This study describes the use of a tumor-targeting peptide that can penetrate the blood-brain barrier and target glioblastoma (GBM). The peptide was conjugated with an insoluble anti-cancer drug, improving solubility and retaining efficacy against GBM stem cells. The study demonstrates enhanced blood-brain barrier permeability and therapeutic targeting to GBM, leading to higher toxicity in GBM cells compared to normal brain tissues and prolonged survival in animal models. This research offers a new approach for targeted therapy in GBM.
Article
Oncology
Moritz Lenschow, Maximilian Lenz, Niklas von Spreckelsen, Julian Ossmann, Johanna Meyer, Julia Kessling, Lukas Nadjiri, Sergej Telentschak, Kourosh Zarghooni, Peter Knoell, Moritz Perrech, Eren Celik, Max Scheyerer, Volker Neuschmelting
Summary: This study aimed to evaluate the necessity of spinal instrumentation in patients with SINS 7-12 with regards to neurological outcome. The results showed that of 331 patients with a SINS of 7-12, 76.1% underwent spinal instrumentation. Neurological outcome did not differ significantly between instrumented and non-instrumented patients. Spinal instrumentation was performed more frequently in SINS 10-12 than in SINS 7-9. The subgroup analysis showed no significant differences in neurological outcome between instrumented and non-instrumented patients in either SINS 7-9 or SINS 10-12. Complications occurred more frequently in instrumented than in non-instrumented patients.
Article
Neurosciences
David Reinecke, Niklas von Spreckelsen, Christian Mawrin, Adrian Ion-Margineanu, Gina Fuertjes, Stephanie T. Juenger, Florian Khalid, Christian W. Freudiger, Marco Timmer, Maximilian Ruge, Roland Goldbrunner, Volker Neuschmelting
Summary: This study aimed to develop a new deep residual convolutional neural network in an automated pipeline using stimulated Raman histology images to predict the presence of tumors in intraoperative tissue samples. The results showed that the residual network could reliably detect the microscopic presence of tumors and differentiate non-tumorous brain tissue, with a short processing time.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Oncology
Anna-Katharina Meissner, Niklas von Spreckelsen, Abdulkader Al Shughri, Anna Brunn, Gina Fuertjes, Marc Schlamann, Matthias Schmidt, Markus Dietlein, Daniel Ruess, Maximilian I. Ruge, Norbert Galldiks, Roland Goldbrunner
Summary: Currently, contrast-enhanced MRI is the preferred method for treatment planning and follow-up in patients with meningioma. However, Ga-68-DOTATATE PET imaging may provide higher sensitivity for detecting meningioma, particularly in cases with complex anatomy or recurrence.
FRONTIERS IN ONCOLOGY
(2022)
Article
Surgery
Moritz Lenschow, Moritz Perrech, Sergej Telentschak, Niklas von Spreckelsen, Julia Pieczewski, Roland Goldbrunner, Volker Neuschmelting
Summary: This retrospective study analyzed data of patients who underwent planned intradural spinal surgery between 2010 and 2020. The study found that CSFL following planned durotomy is a relevant and quantifiable complication risk. Factors such as age and gender are associated with CSFL development, while surgical indication, tumor histology, location, previous intradural surgery, and comorbidities are not. No significant association was found between CSFL development and dural closure technique, timing of mobilization, or placement of epidural drainage.
FRONTIERS IN SURGERY
(2022)
Article
Oncology
Niklas von Spreckelsen, Julian Ossmann, Maximilian Lenz, Lukas Nadjiri, Moritz Lenschow, Sergej Telentschak, Johanna Meyer, Julia Kessling, Peter Knoell, Peer Eysel, Roland Goldbrunner, Moritz Perrech, Max Scheyerer, Eren Celik, Kourosh Zarghooni, Volker Neuschmelting
Summary: Metastatic spinal disease with epidural spinal cord compression (ESCC) is a devastating disease. Treatment regimens often combine surgery, radiotherapy, and medical treatment. Limited data exist on whether decompressive surgery is necessary for neurologically intact patients with ESCC.
Article
Clinical Neurology
Qiangbin Zhu, Niklas von Spreckelsen, Peikun Huang, Jianfeng Zhou, Zhigang Pan, Jinliang Liu, Xiumei Guo, Yu Xiong, Xinyue Huang, Weipeng Hu, Feng Zheng
Summary: This study retrospectively analyzed the efficacy and safety of TIDN surgery in the treatment of pediatric patients with AEDH. The results showed that TIDN puncture combined with hematoma drainage is a safe, effective, and minimally invasive treatment option for pediatric patients with stable consciousness and AEDH.
CLINICAL NEUROLOGY AND NEUROSURGERY
(2023)
Article
Biochemistry & Molecular Biology
Todd Hollon, Cheng Jiang, Asadur Chowdury, Mustafa Nasir-Moin, Akhil Kondepudi, Alexander Aabedi, Arjun Adapa, Wajd Al-Holou, Jason Heth, Oren Sagher, Pedro Lowenstein, Maria Castro, Lisa Irina Wadiura, Georg Widhalm, Volker Neuschmelting, David Reinecke, Niklas von Spreckelsen, Mitchel S. Berger, Shawn L. Hervey-Jumper, John G. Golfinos, Matija Snuderl, Sandra Camelo-Piragua, Christian Freudiger, Honglak Lee, Daniel A. Orringer
Summary: DeepGlioma is a multimodal deep learning approach that utilizes stimulated Raman histology and large-scale public genomic data to accurately predict molecular alterations for diffuse glioma diagnosis.
Article
Oncology
Gina Fuertjes, David Reinecke, Niklas von Spreckelsen, Anna-Katharina Meissner, Daniel Ruess, Marco Timmer, Christian Freudiger, Adrian Ion-Margineanu, Florian Khalid, Konstantin Watrinet, Christian Mawrin, Andriy Chmyrov, Roland Goldbrunner, Oliver Bruns, Volker Neuschmelting
Summary: This study aims to evaluate the autofluorescence of the brain and its neoplasia by stimulated Raman histology (SRH) combined with two-photon fluorescence. The results showed that autofluorescence varies depending on the tissue type and localization, as well as among different brain tumors.
FRONTIERS IN ONCOLOGY
(2023)
Article
Oncology
Peter Knoell, Moritz Lenschow, Maximilian Lenz, Volker Neuschmelting, Niklas von Spreckelsen, Sergej Telentschak, Sebastian Olbrueck, Maximilian Weber, Johannes Rosenbrock, Peer Eysel, Sebastian G. Walter
Summary: This study aimed to identify risk factors for neurological compromise in patients with metastatic spinal disease. The research found that prolonged time to radiation therapy was the main risk factor for this type of neurological compromise.
Meeting Abstract
Oncology
Todd Hollon, Cheng Jiang, Mustafa Nasir-Moin, Akhil Kondepudi, Asadur Chowdury, Wajd Al-Holou, Maria Castro, Pedro Lowenstein, Lisa Irina Wadiura, Georg Widhalm, Volker Neuschmelting, Reinecke David, Niklas Von Spreckelsen, Mitchel S. Berger, John Golfinos, Shawn L. Hervey-Jumper, Sandra Camelo-Piragua, Honglak Lee, Christian Freudiger, Daniel Orringer
Article
Clinical Neurology
Thomas Sauvigny, Henrik Giese, Julius Hoehne, Karl Michael Schebesch, Christian Henker, Andreas Strauss, Kerim Beseoglu, Niklas von Spreckelsen, Jurgen A. Hampl, Jan Walter, Christian Ewald, Aleksandrs Krigers, Ondra Petr, Vicki M. Butenschoen, Sandro M. Krieg, Christina Wolfert, Khaled Gaber, Klaus Christian Mende, Thomas Bruckner, Oliver Sakowitz, Dirk Lindner, Jan Regelsberger, Dorothee Mielke
Summary: The authors analyzed 502 patients in a prospective multicenter database to evaluate early surgery-related complications after cranioplasty. They found that 46% of patients used autologous bone flaps for CP, with titanium, polyetheretherketone, and polymethylmethacrylate being the most common engineered materials.
JOURNAL OF NEUROSURGERY
(2022)
Article
Clinical Neurology
Moritz Lenschow, Niklas von Spreckelsen, Sergej Telentschak, Christoph Kabbasch, Roland Goldbrunner, Stefan Grau
Summary: This study analyzed the risk factors for ventriculostomy-related intracranial hemorrhages (VS-ICH) in endovascular or surgical treatment of ruptured aneurysms, focusing on antithrombotic therapy. The findings suggest an increased risk of VS-ICH in the endovascular group if antiplatelets were required.
NEUROSURGICAL REVIEW
(2022)
