Biodegradable Nanoscale Coordination Polymers for Targeted Tumor Combination Therapy with Oxidative Stress Amplification

Abstract

Nowadays various inorganic nanoparticles that generate highly reactive hydroxyl radical (·OH) on the basis of Fenton‐like catalytic activity of metal ions have been designed for chemodynamic therapy. However, the high level of adaptive antioxidants [glutathione (GSH)] in cancer cells could effectively consume ·OH to compromise the treatment efficiency and biosafety of these inorganic nanoparticles, and this is a general concern in chemodynamic therapy. Herein, a new biodegradable nanoscale coordination polymer (NCP) is developed by integration of cisplatin prodrug (DSCP) and iron (III) ions through a reverse microemulsion method. The DSCP in the NCPs could react with GSH to release free cisplatin, while the iron (III) ions could be reduced by GSH into iron (II) to enable Fenton reaction, subsequently leading to amplified intracellular oxidative stress. After surface modification of polyethylene glycol (PEG) and cyclo[Arg‐Gly‐Asp‐D‐Phe‐Lys(mpa)] peptide (cRGD), Fe‐DSCP‐PEG‐cRGD shows an excellent targeting effect against αvβ3‐integrin overexpressed tumor cells. Furthermore, Fe‐DSCP‐PEG‐cRGD enables significant chemo and chemodynamic therapy with dramatically enhanced therapeutic efficiency in comparison to relative monotherapies. Importantly, Fe‐DSCP‐PEG‐cRGD could be efficiently cleared out from mice through feces and urine postinjection 7 days. The NCP presented in this work is simple and economical, which shows great biodegradability and biosafety for potential clinical translation.

GSH depletion liposome adjuvant for augmenting the photothermal immunotherapy of breast cancer

“…Specifically, ROS can act as a "danger signal" to elicit the activation of DCs by up-regulating the costimulatory molecules, such as CD80 and CD86 for facilitating antigen presentation (8,13). However, there also exist strong antioxidant systems in the intracellular environment, mainly composed of glutathione (GSH), that down-regulate the ROS level (14)(15)(16). It results in immunosuppression and attenuation of antitumor efficacy.…”

Cascaded amplification of intracellular oxidative stress and reversion of multidrug resistance by nitric oxide prodrug based-supramolecular hydrogel for synergistic cancer chemotherapy

“…Although ROS based treatments (including photodynamic therapy [ 56 , 57 ], sododynamic therapy [ 58 , 59 ], and chemodynamic therapy [ 60 , 61 ]) have been vastly developed for cancer therapy, NO has its own advantages by involving in various pathological processes [ 62 ]. In this study, JSK-based supramolecular hydrogel was facilely developed, which could significantly improve the bioavailability through locoregionally sustained NO release.…”

Energy‐converting biomaterials for cancer therapy: Category, efficiency, and biosafety

“…Two‐dimensional (2D)‐based photo‐converted H‐ECBs, such as 2D transition metal dichalcogenides (2D TMDs), MXenes, black phosphorus (BP), boron nanosheets (B), and reduced graphene oxide (rGO), have gained continuous attention due to their strong optical absorption and desired photothermal properties in the NIR region (Figure 6a; Liu, Wu, et al, 2020; Cheng et al, 2014; Kalluru, Vankayala, Chiang, & Hwang, 2016; Ouyang et al, 2019). Among these 2D biomaterials, MXenes including 2D transition metal carbides, nitrides, and carbon nitrides have shown high potentials in cancer treatments due to their excellent biocompatibility, low toxicity, large surface area, strong NIR absorption, and the high electronic conductivity (Li et al, 2020).…”

“…(a) Synthesis and bioapplications of 2D nanomaterials (Reprinted with permission from Liu et al (2020), Copyright 2020 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim), (b) Scheme of Ti 3 C 2 nanosheet exfoliation process (Reprinted with permission from Lin, Gao, Dai, Chen, and Shi (2017), Copyright 2016 American Chemical Society), (c) Schematic illustration of biodegradable Nb 2 C for photo hyperthermia (Reprinted with permission from Lin, Wang, et al (2017), Copyright 2017 American Chemical Society), (d) Schematic representation of the degradation process of the BPQDs/PLGA NSs (Reprinted with permission from Shao et al (2016), Copyright 2016 Nature Publishing Group), (e) Schematic illustration of the procedure of nanostructures and combined targeted therapy (Reprinted with permission from Zeng et al (2018), Copyright 2018 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim)…”