On-demand assembly of polymeric nanoparticles for longer-blood-circulation and disassembly in tumor for boosting sonodynamic therapy

作者：Mei Wen, Nuo Yu, Shiwen Wu, Mengmeng Huang, Pu Qiu, Qian Ren, Meifang Zhu, Zhigang Chen · 发表于：Bioactive Materials · 年份：2022 · DOI：10.1016/j.bioactmat.2022.03.009 · 被引用次数：81 · 研究领域：Nanoplatforms for cancer theranostics、Nanoparticle-Based Drug Delivery、Photoacoustic and Ultrasonic Imaging

Sonodynamic therapy (SDT) is one of the promising strategies for tumor therapy, but its application is usually hindered by fast clearance in blood-circulation, abnormal tumor microenvironment, and inefficient generation of reactive oxygen species. To solve these problems, we proposed an on-demand assembly-disassembly strategy, where the assembly is favorable for longer-blood-circulation and then the disassembly in tumor is favorable for boosting SDT. Hematoporphyrin monomethyl ether (HMME) as the model of organic sonosensitizers were conjugated with hyaluronic acid (HA). Then HA-HMME was mixed with catalase (CAT) and assembled into polymeric nanoparticles (CAT@HA-HMME NPs) with size of ∼80 nm. CAT@HA-HMME NPs exhibit good biocompatibility and a longer blood half-time (t 1/2 = 4.17 h) which is obviously longer than that (∼0.82 h) of HMME molecules. After HA receptor-mediated endocytosis of cancer cells, CAT@HA-HMME NPs can be cleaved by endogenous hyaluronidase, resulting in the on-demand disassembly in tumor to release HA-HMME molecules and CAT. The CAT catalyzes the endogenous H 2 O 2 into O 2 to relieve the hypoxic microenvironment, and the released HA-HMME exhibits a higher ROS generation ability, greatly boosting SDT for the inhibition of tumor growth. Therefore, the on-demand assembly-disassembly strategy may provide some insight in the design and development of nanoagents for tumor therapy.