Reactive Oxygen Species Responsive Cleavable Hierarchical Metallic Supra‐Nanostructure

Abstract

A reactive oxygen species (ROS) responsive cleavable hierarchical metallic supra‐nanostructure (HMSN) is reported. HMSN structured with thin branches composed of primary gold (Au) nanocrystals and silver (Ag) nano‐linkers is synthesized by a one‐pot aqueous synthesis with a selected ratio of Au/Ag/cholate. ROS responsive degradability of HMSN is tested in the presence of endogenous and exogeneous ROS. Significant ROS‐responsive structural deformation of HMSN is observed in the ROS exposure with hydrogen peroxide (H2O2) solution. The ROS responsiveness of HMSN is significantly comparable with negligible structural changes of conventional spherical gold nanoparticles. The demonstrated ROS responsive degradation of HMSN is further confirmed in various in vitro ROS conditions of each cellular endogenous ROS and exogeneous ROS generated by photodynamic therapy (PDT) or X‐ray radiation. Then, in vivo ROS responsive degradability of HMSN is further evaluated with intratumoral injection of HMSN and exogeneous ROS generation via PDT in a mouse tumor model. Additional in vivo biodistribution and toxicity of intravenously administrated HMSN at 30‐day post‐injection are investigated for potential in vivo applications. The observed ROS responsive degradability of HMSN will provide a promising option for a type of ROS responsive‐multifunctional nanocarriers in cancer treatment and various biomedical applications.

Stimuli-activatable nanomedicine meets cancer theranostics

“…Radiation. Radiation (e.g., X-ray, γ-ray, other charged particles) with an intensive energy can directly induce the degradation of prodrugs and inorganic nanostructures, such as sulfonyl azide- and phenyl azide-caged prodrugs of pazopanib and doxorubicin 57 and a hierarchical metallic supra-nanostructure with thin Au branches connected with Ag nano-linkers 58 . Furthermore, radiation can indirectly generate ROS or hydrated electrons in tumors, resulting in the breakage of ROS-activatable linkers or quaternary ammonium masking groups 59 .…”

Dual-Responsive Smart Nano-Platform Targeting Peptide Modifications Synergistically Enhances Multimodal Therapy for Liver Cancer

“…The photosensitizer internalized by tumor cells is excited by the laser, and this energy is transferred to the surrounding oxygen, leading to the generation of highly reactive singlet oxygen species. The singlet oxygen oxidizes cellular biomolecules to produce cytotoxic effects, leading to cell damage or even death, thus achieving anti-tumor effects [12,13]. However, both PTT and PDT have some inherent drawbacks.…”

Supramolecular Theranostic Nanomedicine for In Situ Self-Boosting Cancer Photochemotherapy

“…Because of the diverse pathogenesis pathways and tumor heterogeneity, drug resistance is another thorny problem faced by conventional chemotherapeutic nanomedicine. Hence, chemotherapy alone cannot ensure the optimal success for tumor treatment. − Comparatively, laser irradiation-mediated photodynamic therapy (PDT), a noninvasive and spatial-temporally controllable therapeutic modality, is able to transform oxygen into reactive oxygen species (ROS), directly causing cell damage and even death without induction of drug resistance. − Although PDT is efficient in ablating local tumors, its activity is invalid for the distal tumors; thereby, tumor recurrence and metastasis are accompanied by PDT. − A combination of systemic chemotherapy and PDT, termed as photochemotherapy, has now thrived as a high-efficiency strategy to eliminate primary and distal tumors. − In addition, ROS generated by photosensitizers (PSs) not only can serve as a weapon for PDT but also can cleave thioketal bond of the prodrug to release drugs in a manner of “on demand”. − Therefore, nanoplatforms combining ROS-responsive chemotherapy and PDT are promising candidates to achieve precise drug release and eliminate drug resistance.…”