pH and Glutathione Synergistically Triggered Release and Self-Assembly of Au Nanospheres for Tumor Theranostics

Abstract

Theranostic agents based on near-infrared absorption which integrate both imaging and therapeutic functions have attracted considerable attention. However, because of the interference signal, indiscriminate treatment usually causes side effects on normal tissues during tumor treatment. To address this limitation, we propose a new synergistically triggered mechanism, release and self-assembly of Au nanospheres, for tumor theranostics based on the synergistic effect of H+ and glutathione on the tumor microenvironment. In vitro experiments reveal that Au nanospheres release from Au@ZIF-8 at a high concentration of H+ or glutathione. Importantly, Au aggregation only appears in the synergistic effect of glutathione and lower pH and exhibits strong coupling plasmonic resonance absorption in the near-infrared region and can be used as the theranostics agent. This statement was further verified by biological transmission electron microscopy and in vivo imaging. Au@ZIF-8 is stable and produces no photoacoustic signal in normal tissue; in contrast, in the presence of overexpressed glutathione and H+, Au nanospheres release from Au@ZIF-8, assemble to aggregates, and exhibit a strong signal at the tumor site for imaging and efficient photothermal therapy. This work provides a new strategy for designing theranostic agents with sequentially responsive steps to avoid interference diagnosis signals from normal tissues and reduce damage to normal tissue during treatment.

Recent advances in selective photothermal therapy of tumor

“…As a proof of concept study, the penetration depth of a 405 nm laser remains limited, but the current strategy for manipulating Au particles in vivo can be extended to other types of light-triggered assembly nanoparticles, which can be triggered by lights with wavelengths that are more suitable for clinical applications. Qiwei Tian and Shiping Yang et al [ 68 ] proposed a novel synergistic triggering mechanism to realize the self-assembly of gold nanospheres. Au@ZIF-8 does not produce photoacoustic signal and photothermal conversion capability in normal tissue.…”

Stereocomplex Polylactide for Drug Delivery and Biomedical Applications: A Review

“…Non-covalent interactions, such as electrostatic interactions, hydrogen bonding, and hydrophobic-hydrophobic interactions are driving forces to induce self-assembly of amphiphilic block copolymers. The stability of the self-assembly can be influenced by several environmental factors, including the pH, temperature, polymer concentration, and ionic strength [ 22 , 23 , 24 , 25 ]. Bishara et al synthesized stereocomplex particles composed of an enantiomeric triblock copolymer (PLA-PEG 2000 -PLA) by blending in acetonitrile solutions [ 26 ].…”

Engineering a Smart Agent for Enhanced Immunotherapy Effect by Simultaneously Blocking PD‐L1 and CTLA‐4

“…ZIF-8, which is a metalorganic framework formed by zinc (Zn 2+ ) and imidazole, [11,12] is a widely used smart nano-delivery agent, as it can be rapidly degraded by weakly acidic and highly expressed glutathione (GSH) in tumors. [13][14][15] For example, An et al [16] reported an engineered smart agent based on ZIF-8-coated gold nanospheres. In normal tissues, the ZIF-8 coating is very stable and prevents the aggregation of the gold nanospheres; however, the nanospheres are released in the tumor owing to destruction of ZIF-8.…”

“…[ 13 , 14 , 15 ] For example, An et al. [ 16 ] reported an engineered smart agent based on ZIF‐8‐coated gold nanospheres. In normal tissues, the ZIF‐8 coating is very stable and prevents the aggregation of the gold nanospheres; however, the nanospheres are released in the tumor owing to destruction of ZIF‐8.…”