Research Progress of Multicomponent Co-Loaded Nanomedicine Delivery Systems for Tumor Immunotherapy

Tianying Sun,1,* Chuanguo Liu,2,* Jiang Zhu,1 Kai Gong,1 Mengzhen Xu,1 Qingjun Zhu,1,3 Hong Guo1,41Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 2Research Institute of Marine Traditional Chinese Medicine (Qingdao Academy of Chinese Medical Sciences), Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 3Key Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Jinan, Shandong, People’s Republic of China; 4Linqu County Hospital of Traditional Chinese Medicine, Weifang, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qingjun Zhu; Hong Guo, Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China, Tel +86-186-1528-8322; +86-135-8908-0261, Email zhuqingjuncn@hotmail.com; 13589080261@163.comAbstract: Tumor immunotherapy has substantially advanced cancer treatment by activating or enhancing the antitumor immune response. However, tumor heterogeneity, the immunosuppressive tumor microenvironment (TME), and therapeutic resistance limit the efficacy of single-agent immunotherapy, making mechanistically complementary multicomponent combination strategies a rational approach to improve therapeutic outcomes. Conventional drug combinations are often constrained by differences in their physicochemical properties and pharmacokinetics, which hinder precise control of predefined synergistic ratios at the target site. Multicomponent co-loaded nanomedicine delivery systems have emerged as a promising platform capable of co-delivering therapeutics with distinct mechanisms of action to the TME at defined ratios. Such systems can integrate established immunotherapeutic agents with conventional therapeutic agents that exert experimentally supported immunomodulatory effects and, through spatiotemporally coordinated delivery and release, achieve complementary tumor control and immune activation by enhancing antigen presentation, reversing immunosuppression, or inducing immunogenic cell death. This review systematically summarizes recent advances in multicomponent co-loaded nanomedicine systems for tumor immunotherapy, with a focus on design principles, component selection, ratio optimization, release kinetics, and immunomodulatory mechanisms. We further discuss key challenges, including formulation compatibility, reproducibility, safety, scalable manufacturing, and clinical translation, with the aim of providing a rational framework and practical guidance for the development of effective and safe nanomedicine-based combination immunotherapies.Keywords: tumor immunotherapy, multicomponent co-loading, combination immunotherapy, tumor microenvironment, drug delivery