Recent developments in chemodrug-loaded nanomedicines and their application in combination cancer immunotherapy

Abstract

Background: In recent studies of cancer therapies, chemodrugs have attracted interest, acting not only as traditional chemotherapeutic agents but also as anticancer immune-activating agents. Specific types of chemodrugs have been demonstrated to exhibit superior anticancer efficacy to others through directly exerting toxic effects on cancer cells and indirectly by inducing immunogenic cell death (ICD) to recruit immune cells to kill them. However, chemodrug-based ICD has not yet achieved satisfactory therapeutic outcomes because of various limitations, including the poor tumor delivery efficiency of chemodrugs, the strong resistance of tumor tissues to chemodrugs, and the immunosuppressive tumor microenvironment. Area covered: This review briefly introduces ICD-inducing chemodrugs and their properties, and then explains the advantages of nanomedicine in ICD-inducing chemodrug delivery. Further, studies on chemodrug-loaded nanomedicine-based combined immunotherapy are discussed, with a focus on the cooperative effect of ICD induction with other co-administered immunotherapeutic modalities. Expert opinion: It is possible to obtain better pharmacokinetic properties and tumor accumulation efficiency when using chemodrug-loaded nanomedicines compared with free chemodrugs, resulting in stronger ICD-inducing effects. The tumor-targeting efficiency of nanomedicines can be further improved by their modification with active targeting or tumor stimuli-responsive moieties while diminishing their undesirable biodistribution. Nanomedicines also facilitate the simultaneous delivery of ICD-inducing chemodrugs and other immunotherapeutic agents; these act synergistically to enhance the efficacy of ICD-based combined immunotherapy, even against highly drug-resistant and immunosuppressive tumors. Nanomedicine is expected to provide a promising approach to overcoming the challenges of ICD-inducing chemodrug-based combination cancer immunotherapy. © 2023, The Author(s) under exclusive licence to The Korean Society of Pharmaceutical Sciences and Technology.