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Review
. 2024 May 21:19:4533-4568.
doi: 10.2147/IJN.S455213. eCollection 2024.

Nanoparticle-Mediated Synergistic Chemoimmunotherapy for Cancer Treatment

Xiaoxue Lang  1 , Xiangtao Wang  1 , Meihua Han  1 , Yifei Guo  1   2   3   4
Affiliations
Review

Nanoparticle-Mediated Synergistic Chemoimmunotherapy for Cancer Treatment

Xiaoxue Lang et al. Int J Nanomedicine. .

Abstract

Until now, there has been a lack of effective strategies for cancer treatment. Immunotherapy has high potential in treating several cancers but its efficacy is limited as a monotherapy. Chemoimmunotherapy (CIT) holds promise to be widely used in cancer treatment. Therefore, identifying their involvement and potential synergy in CIT approaches is decisive. Nano-based drug delivery systems (NDDSs) are ideal delivery systems because they can simultaneously target immune cells and cancer cells, promoting drug accumulation, and reducing the toxicity of the drug. In this review, we first introduce five current immunotherapies, including immune checkpoint blocking (ICB), adoptive cell transfer therapy (ACT), cancer vaccines, oncolytic virus therapy (OVT) and cytokine therapy. Subsequently, the immunomodulatory effects of chemotherapy by inducing immunogenic cell death (ICD), promoting tumor killer cell infiltration, down-regulating immunosuppressive cells, and inhibiting immune checkpoints have been described. Finally, the NDDSs-mediated collaborative drug delivery systems have been introduced in detail, and the development of NDDSs-mediated CIT nanoparticles has been prospected.

Keywords: NDDSs; chemoimmunotherapy; chemotherapy; immunotherapy.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

None
Graphical abstract
Figure 1
Figure 1
Immune checkpoint inhibitors are used to treat cancer. CD8+ T cells express PD-1, CTLA-4, TIM3 and LAG3. CTLA-4 and TIM3 were highly expressed on Tregs. TIM3 was significantly expressed in TAMs and NK cells. Binding of PD-1 to PD-L1 expressed on tumor cells can promote apoptosis of CD8+ T cells. CTLA-4 inhibits T cell proliferation and induces Tregs activity by binding to CD80/86 in APCs. The interaction between TIM3 and the ligand galactin-9 on the surface of MDSCs also induced T cell apoptosis. Reprinted with permission from Chen Y, Hu H, Yuan X, Fan X, Zhang C. Advances in immune checkpoint inhibitors for advanced hepatocellular carcinoma. Front Immunol. 2022;13:896752. doi:10.3389/fimmu.2022.896752 . Copyright © 2022.
Figure 2
Figure 2
Overview of adoptive T cell therapy in TCR. Tumor-reactive lymphocytes can be isolated from the patient’s tumor mass or peripheral blood. T cells can be expanded in vitro and re-infused back into the patient, for example in TILs therapy. The tumor-reactive T cell receptor (TCR) gene can be isolated/sequenced via a vector and transferred into recipient T cells to redirect T cell specificity for tumor epitopes. Reprinted with permission from Manfredi F, Cianciotti BC, Potenza A, et al. TCR redirected T cells for cancer treatment: achievements, hurdles, and goals. Front Immunol. 2020;11:1689. doi:10.3389/fimmu.2020.01689. Copyright © 2020.
Figure 3
Figure 3
Overview of VLP-based vaccine expression, purification, and formulation. (a) Production stage: clone interested viral structural genes and express viral proteins with self-assembly capability in a suitable expression platform. (b) Purification stage: downstream processing, such as clarification and purification, and finally obtaining the purified complete VLP. (c) Formulation stage: adjuvants and other ingredients are added to the vaccine formulation to achieve safe and effective vaccination products. Reprinted with permission from Nooraei S, Bahrulolum H, Hoseini ZS, et al. Virus-like particles: preparation, immunogenicity and their roles as nanovaccines and drug nanocarriers. J Nanobiotechnol. 2021;19(1):59. doi:10.1186/s12951-021-00806-7. Copyright © 2021.
Figure 4
Figure 4
Mechanism of action of oncolytic virus. The virus replication in tumor cells triggers the ICD, which causes the release of a series of cytokines (IFNs, TNF-α, IL-6, IL-1) and the activation of immune cells (T cells, NK cells, DC cells). OVs can infect and dissolve vascular endothelial cells, affect tumor blood supply, and reshape TME. Reprinted with permission from Volovat SR, Scripcariu DV, Vasilache IA, et al. Oncolytic virotherapy: a new paradigm in cancer immunotherapy. Int J Mol Sci. 2024;25(2):1180. doi:10.3390/ijms25021180. Copyright © 2024.
Figure 5
Figure 5
Interaction of IL-2/IL-2R signal transduction in TME. Lower levels of IL-2 can promote the regulation of the microenvironment, which may promote tumor growth, while higher levels can act as a stimulant for immune cells and promote tumor elimination. On the one hand, it can stimulate Tregs to inhibit the anti-tumor response; on the other hand, it can induce the infiltration of CTL and NK cells, thus enhancing the anti-tumor immune response. The arrows of different sizes in the figure indicate the different intensities of IL-2 production and its effect on different cell types. Reprinted with permission from Muhammad S, Fan T, Hai Y, Gao Y, He J. Reigniting hope in cancer treatment: the promise and pitfalls of IL-2 and IL-2R targeting strategies. Mol Cancer. 2023;22(1):121. doi:10.1186/s12943-023-01826-7. Copyright © 2023.
Figure 6
Figure 6
Potential mechanism of HDAC2i blocking PD-1/PD-L1. HDAC2i can affect PD-L1 by blocking PD-L1 acetylation-dependent nuclear translocations, reprogramming the expression of immune response-related genes, and regulating IFN-γ. Reprinted with permission from Han R, Ling C, Wang Y, Lu L. Enhancing HCC treatment: innovatively combining HDAC2 inhibitor with PD-1/PD-L1 inhibition. Cancer Cell Int. 2023;23(1):203. doi:10.1186/s12935-023-03051-0. Copyright © 2023.
Figure 7
Figure 7
Chemotherapy drugs drive the cancer immune cycle. (A) chemotherapy drugs induce ICD; (B) promote CD8+ T cell infiltration; (C) inhibit immunosuppressive cells. Reprinted with permission from Li JY, Chen YP, Li YQ, Liu N, Ma J. Chemotherapeutic and targeted agents can modulate the tumor microenvironment and increase the efficacy of immune checkpoint blockades. Mol Cancer. 2021;20(1):27. doi:10.1186/s12943-021-01317-7. Copyright © 2021.
Figure 8
Figure 8
A timeline for FDA-approved products for chemoimmunotherapy from 2020 to 2024.
See this image and copyright information in PMC

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This research was funded by CAMS Innovation Fund for Medical Sciences (No. 2022-I2M-2-002, No. 2021-I2M-1-031, No. 2021-I2M-1-071), Hainan Province Science and Technology Special Fund (No. ZDYF2023SHFZ140).

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