TOPIC INSIGHT • 專題探討 2023 UMAGAZINE 27 • 澳大新語 45 a very high temperature, yet no visible damage was found in the surrounding tissues apart from the tumour. This again indicates that most of the supramolecular nanomedicine had reached its intended target, the tumour tissue. Conversely, the tumour sites of the two other groups of mice showed a very modest temperature increase. Accordingly, when combined with anti-PD-L1, an immune checkpoint inhibitor, the bacteria-mimetic supramolecular nanomedicine exhibited the best therapeutic effect against melanoma, by having nearly eliminated all tumours from mice. Towards Validation and Development In 2022, the leading journal Science Advances published the team’s paper, titled ‘In vivo Hitchhiking of Immune Cells by Intracellular Self-assembly of Bacteria-mimetic Nanomedicine for Targeted Therapy of Melanoma.’ Prof Wang is the lead corresponding author and Simon Lee, distinguished professor in the ICMS, is the co-corresponding author. Postdoctoral fellow Gao Cheng and master’s student Wang Qingfu are the co-first authors. UM PhD students Li Junyan and Cheryl Kuong, research assistant Wei Jianwen, and postdoctoral fellow Xie Beibei also made important contributions to this research project. The project was funded by the Dr Stanley Ho Medical Development Foundation, the Macao Special Administrative Region Science and Technology Development Fund, the National Natural Science Foundation of China, and the Ministry of Education Frontiers Science Center for Precision Oncology at UM. The research project was showcased in the 2022 Guangdong-Hong Kong-Macao Greater Bay Area High-value Patent Portfolio Layout Competition and received a silver medal, as one of only 25 gold and silver awardees, surpassing thousands of other entries. This success has drawn the attention of several companies in mainland China, which have expressed interest in partnering with the team to further develop and test the efficacy and safety of this innovative method. Supramolecular Technology: A Versatile Tool to Improve Disease Therapies Prof Wang’s team has conducted cutting-edge studies on the application of supramolecular by lysosomal enzymes, paving the way for supramolecular assemblies of β-CD-modified and Ada-modified GNPs into supramolecular aggregates. These aggregates are formed via supramolecular host-guest interactions, also personified as ‘hands-holding’. ‘The cancer tissue is the destination, the macrophages are the transportation vehicles, and the supramolecular medicines are the hitchhikers. Without the vehicles, the hitchhikers alone may not efficiently reach their intended destination,’ says Prof Wang. Photothermal Cancer Therapy Inside the macrophages, the supramolecular aggregates of GNPs also gain a photothermal property via ‘plasmonic effects’ as a result of the close contact of the gold surface of these nanoparticles. This means that they heat up when exposed to light, which doctors can use to their advantage. They can direct a specific laser wavelength to the site of the tumour once sufficient nanomedicines have gathered in them. This treatment, known as photothermal therapy (PTT), generates high temperatures that destroy the cancer tissue and cells. The research team tested the efficacy of the bacteria-mimetic nanomedicine by performing PTT on mice with melanoma, a type of skin cancer. The mice were divided into three groups. The first group received gold nanoparticles without E. coli outer membrane vesicles, the second group received gold nanoparticles coated with E. coli outer membrane vesicles, and the third group received a combination of GNPs coated with an E. coli membrane vesicle, with half of the GNPs modified with host molecules and the other half modified with guest molecules. After injection of these formulations, the first group of mice showed minimal accumulation of GNPs in the tumour, the second group exhibited improved accumulation due to the macrophage-hitchhiking driven by bacteria-mimics, while the third group showed a significant amount of GNPs deposited in the tumour, attributed to the intracellular supramolecular aggregation of GNPs that minimised premature loss during macrophage-hitchhiking delivery. When irradiated with laser, the solid tumour tissue in the third group of mice reached
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