Work

Intelligent nanocatalyst mediated lysosomal ablation pathway to coordinate the amplification of tumor treatment

Year: 2024

Type: article

Abstract: The production of reactive oxygen species (ROS) is susceptible to external excitation or insufficient supply of related participants ( e.g. , hydrogen peroxide (H 2 O 2 ) and sensitizer), liming ROS-driven tumor treatment. Additionally, the lysosomal retention effect severely hinders the utilization of ROS-based nanosystems and severely restricted the therapeutic effect of tumors. Therefore, first reported herein an intelligent nanocatalyst, TCPP-Cu@MnO x ((Mn II ) 1 (Mn III ) 2.1 (Mn IV ) 2.6 O 9.35 ), and proposed a programmed ROS amplification strategy to treat tumors. Initially, the acidity-unlocked nanocatalyst was voluntarily triggered to generate abundant singlet oxygen ( 1 O 2 ) to mediate acid lysosomal ablation to assist nanocatalyst escape and partially induce lysosomal death, a stage known as lysosome-driven therapy. More unexpectedly, the high-yielding production of 1 O 2 in acid condition (pH 5.0) was showed compared to neutral media (pH 7.4), with a difference of about 204 times between the two. Subsequently, the escaping nanocatalyst further activated H 2 O 2 -mediated 1 O 2 and hydroxyl radical (•OH) generation and glutathione (GSH) consumption for further accentuation tumor therapy efficiency, which is based on the Fenton-like reaction and Russell reaction mechanisms. Therefore, in this system, a program-activatable TCPP-Cu@MnO x nanocatalyst, was proposed to efficiently destruct organelle-lysosome via 1 O 2 inducing, and stimulated H 2 O 2 conversion into highly toxic 1 O 2 and •OH in cytoplasm, constituting an attractive method to overcome limitations of current ROS treatment. First reported herein a spontaneous acid activation 1 O 2 generation, intelligent TCPP-Cu@MnO x nanocatalyst, to mediate acid lysosomal ablation, thereby further activating H 2 O 2 -mediated 1 O 2 and •OH generation for accentuation tumor therapy efficiency, based on a Fenton-like reaction and Russell reaction mechanisms in cytoplasm. More unexpectedly, the high-yielding production of 1 O 2 by acid condition (pH 5.0) was showed compared to neutral media (pH 7.4), with a difference of about 204 times between the two. Additionally, we proposed an programmatic multi-channel ROS-induced mechanisms, including pH-unlocked O 2 electron transfer effect, Fenton-like reaction and Russell Mechanism. Thus, the proposed nanocatalyst efficiently destruct organelle-lysosome strategy and stimulate the series of intramatoma ROS production, constituting an attractive method to overcome limitation of current ROS treatment. • In this research, the significance and novelty of our findings are highlighted as below: • Nanocatalyst exhibit medium stability, TME-excited degradation and enzyme-like catalysis. • PH-activated 1 O 2 generated nanocatalyst induce LMP to enhance tumor ablation. • Nanocatalyst catalyze the production of ROS in tumor cell through multiple channels. • Programmed ROS production strategy can circumvent ROS therapy limitations.

Source: Materials Today Bio

DOI: 10.1016/j.mtbio.2024.101299