Arsenic Prodrug-Mediated Tumor Microenvironment Modulation Platform for Synergetic Glioblastoma Therapy

Abstract

Glioblastoma (GBM) has a distinct internal environment characterized by high levels of glutathione (GSH) and low oxygen partial pressure, which significantly restrict most drugs’ effectiveness. Arsenic-based drugs are emerging candidates for treating solid tumors; however, relatively high doses in solo systems and inconsistent complementary systems severely damage the normal tissues. We proposed a novel covalently conjugated strategy for arsenic-based therapy via arsenic-boronic acid complex formation. The boronic acid was modified on silver (AgL) to capture AsV under an alkaline condition named arsenate plasmonic complex (APC) with a distinct Raman response. The APC can precisely release the captured AsV in lysosomal acidic pH that specifically targets TME to initiate a multimodal therapeutic effect such as GSH depletion and reactive oxygen species generation. In addition, GSH activation leads to subconverted AsV into AsIII, which further facilitated glutathione peroxidase (GPx) and superoxide dismutase inhibition, whereas the tumor selective etching of the silver core triggered by endogenous H2O2 that can oxidize to generate highly toxic Ag ions produces and supplies O2 to help the alleviated hypoxia. Both in vitro and in vivo data verify the APC-based chemotherapy paving the way for efficient nanomedicine-enabled boronate affinity-based arsenic chemotherapeutics for on demand site-specific cancer combination treatment of GBM tumors.

The Role of Purine Metabolism-Related Genes PPAT and IMPDH1 in the Carcinogenesis of Intrahepatic Cholangiocarcinoma Based on Metabonomic and Bioinformatic Analyses

“…As cancer therapy is moving toward personalization, one approach is to use anticancer drugs encapsulated in nanoparticles, such as liposomes or nanopolymers, and these are taken up by ICC via endocytosis, leading to higher intracellular concentrations and enhanced anticancer drug efcacy [28]. Arsenate plasmonic complex-based chemotherapy is paving the way for efcient nanomedicineenabled boronate afnity-based arsenic chemotherapeutics for on demand site-specifc cancer combination treatment of glioblastoma [29]. Te application of nanomedicine is also expected to bring new hope to liver cancer [30] and pancreatic ductal adenocarcinoma treatment [31,32].…”

Identification of a Novel Amino Acid Metabolism-Related Gene Risk Signature as a Prognostic and Immunotherapeutic Efficiency Predictor for Colorectal Cancer

“…Previous studies have investigated that tumor metabolic reprogramming affects the survival and proliferation of cancer cells themselves as well as exerting a key in uence on the TME [9]. Cancer metabolic reprogramming and the TME both involved extensive immune cells and microbiota [39]. And the interaction of them is considered to be a critical mechanism to regulate the progression and migration of cancer.…”

Nanomedicine Strategies in Conquering and Utilizing the Cancer Hypoxia Environment

“…Yan and co-workers fabricated a GSH-triggered arsenate plasmonic composite (APC) that was designed by modified on silver (AgL) with boronic acid and then captured AsV. 216 The APC can release the As−V in lysosomal acidic pH that precisely targets TME to initiate GSH depletion and ROS generation. In addition, GSH activation leads to subconverted As−V into As−III, which further facilitates GSH peroxidase (GPx) and superoxide •− for photothermally enhanced tumor catalytic therapy.…”

“…Meanwhile, under the influence of NIR therapy, catalase-like Au nanoenzymes catalyze H 2 O 2 for O 2 supply to relieve hypoxic TME and provide harmful 1 O 2 against cancer cells. Yan and co-workers fabricated a GSH-triggered arsenate plasmonic composite (APC) that was designed by modified on silver (AgL) with boronic acid and then captured AsV . The APC can release the As–V in lysosomal acidic pH that precisely targets TME to initiate GSH depletion and ROS generation.…”