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Proteasome inhibition is accepted as a new strategy for cancer therapy. Despite being a big breakthrough in multiple myeloma therapy, carfilzomib (CFZ), a second\u2010in\u2010class proteasome inhibitor is still unsatisfactory for solid tumor and metastasis therapy. In this study, hollow titanium nitride (TiN) nanoshells are synthesized as a drug carrier of CFZ. The TiN nanoshells have a high loading capacity of CFZ, and their intrinsic inhibitory effect on autophagy synergistically enhances the activity of CFZ. Due to an excellent photothermal conversion efficiency in the second near\u2010infrared (NIR\u2010II) region, TiN nanoshell\u2010based photothermal therapy further induces a synergistic anticancer effect. In vivo study demonstrates that TiN nanoshells readily drain into the lymph nodes, which are responsible for tumor lymphatic metastasis. The CFZ\u2010loaded TiN nanoshell\u2010based chemo\u2010photothermal therapy combined with surgery offers a remarkable therapeutic outcome in greatly inhibiting further metastatic spread of cancer cells. These findings suggest that TiN nanoshells act as an efficient carrier of CFZ for realizing enhanced outcomes for proteasome inhibitor\u2010based cancer therapy, and this work also presents a \u201ccombined chemo\u2010phototherapy assisted surgery\u201d strategy, promising for future cancer treatment.<\/jats:p>","DOI":"10.1002\/smll.202200522","type":"journal-article","created":{"date-parts":[[2022,6,24]],"date-time":"2022-06-24T08:30:29Z","timestamp":1656059429000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Chemo\u2010Phototherapy with Carfilzomib\u2010Encapsulated TiN Nanoshells Suppressing Tumor Growth and Lymphatic Metastasis"],"prefix":"10.1002","volume":"18","author":[{"given":"Xuan","family":"Wu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Quality Research in Chinese Medicine Macau Institute for Applied Research in Medicine and Health Macau University of Science and Technology 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