Supramolecular Self-Assemblies with Self-Supplying H₂O₂ and Self-Consuming GSH Property for Amplified Chemodynamic Therapy

Abstract

Fe-based chemodynamic therapy (CDT) has become one potential method for cancer therapy due to its lower side effect and tumor-specific property. During the process of CDT, the lack of active targeting and biodegradable ability, insufficient endogenous H2O2, and overexpressed GSH in the tumor were responsible for the unsatisfactory therapeutic performance. Hence, we report host–guest interaction-based supramolecular polymers (HGSPs) that were constructed with the biomacromolecule β-cyclodextrin-grafted hyaluronic acid (HA-CD) as the active targeting host unit and hydrophobic ROS-responsive ferrocene-(phenylboronic acid pinacol ester) (Fc-BE) as the guest unit. HGSPs can further self-assemble into self-assemblies (HGSAs) and encapsulate PA as the prooxidant. After CD44-receptor-mediated cellular internalization, HGSAs could disassemble and release PA to elevate the H2O2 level for the production of higher cytotoxic hydroxyl radicals (•OH) through the Fc-induced Fenton reaction. Moreover, quinone methide (QM) was generated to downregulate antioxidant GSH. The enhancement of H2O2 and consumption of GSH were favorable for CDT due to the amplified oxidative stress. In vivo experimental results indicated that HGSAs@PA might be used as an active targeting amplified CDT agent.

Host–Guest Interaction-Based Supramolecular Self-Assemblies for H2O2 Upregulation Augmented Chemiluminescence Resonance Energy Transfer-Induced Cancer Therapy

“…It is worthy to be noted that cinnamaldehyde (CA) could upregulate H 2 O 2 levels through the activation of NADPH oxidase. − However, the rapid oxidation of the aldehyde group always led to their short life in blood, restricting their further application. To overcome these barriers, CA was grafted onto HA with hydrazone bonds.…”

Multifunctional nanomedicines-enabled chemodynamic-synergized multimodal tumor therapy via Fenton and Fenton-like reactions

“…Focusing on the problems as mentioned above, several strategies have been developed to enhance the therapeutic efficacy of CDT, some of which are listed in Table 1. For example, modulating the TME states, such as lowing the pH of the tumor 22 , designing Fenton reaction reagents that are less dependent on pH 23 , 24 , increasing the level of H 2 O 2 17 , 25 , 26 , or consuming GSH in the tumor 27 , 28 , can improve the therapeutic outcome of CDT. Besides, optimizing the morphology and interface properties of the catalysts could enhance their catalytic ability, since the chemical composition, size, and aggregation of the nanocatalysts have a great impact on the catalytic rate and activity of the Fenton reaction 29 .…”

Drug Self‐Delivery Systems: Molecule Design, Construction Strategy, and Biological Application

“…DSDSs have been widely used in the fields of biomedicine, including oncotherapy, [18][19][20] antibacterial, [21,22] antiinflammatory, [23][24][25] and anti-viral activity. [26,27] The novel strategy underlying DSDSs function has recently been rapidly developed, leading to efficient drug delivery, decreased intrinsic toxicity of the agents, and thus increased efficacy of treatment.…”