Integration of active ingredients from traditional Chinese medicine with nano-delivery systems for tumor immunotherapy

Abstract

Tumor immune escape presents a significant challenge in cancer treatment, characterized by the upregulation of immune inhibitory molecules and dysfunction of immune cells. Tumor immunotherapy seeks to restore normal anti-tumor immune responses to control and eliminate tumors effectively. The active ingredients of traditional Chinese medicine (TCM) demonstrate a variety of anti-tumor activities and mechanisms, including the modulation of immune cell functions and inhibiting tumor-related suppressive factors, thereby potentially enhancing anti-tumor immune responses. Furthermore, nano-delivery systems function as efficient carriers to enhance the bioavailability and targeted delivery of TCM active ingredients, augmenting therapeutic efficacy. This review comprehensively analyzes the impact of TCM active ingredients on the immune system and explores the synergistic application of nano-delivery systems in combination with TCM active ingredients for enhancing tumor immunotherapy.

Keywords: Active ingredients; Drug delivery; Nanocarriers; TCM; Tumor immunotherapy.

Fig. 1

Schematic illustration of the modulation of the immune system and the various nanocarriers used in nano-delivery systems for active ingredients in TCM

Fig. 2

Schematic diagram of the regulatory mechanisms of immune cells

Fig. 3

Lipid-based nano-delivery systems with TCM active ingredients. A Schematic diagram of thermosensitive liposomes for melanoma chemoimmunotherapy. Reproduced with permission of Ref. [208]. Copyright © 2022 Elsevier. B Tumor images, C flow cytometry analysis and quantitation, and D western blot analysis of CEL NE treatment on B16F10 bilateral tumor model. Reproduced with permission of ref. [165]. Copyright © 2020 Elsevier

Fig. 4

Polymer-based nano-delivery systems with TCM active ingredients. A Schematic diagram of co-delivery polymer micelles to improve immunosuppressive TME. B mRNA levels of M1-TAM and M2-TAM markers and C PD-L1 and PKM2 expression after treatment in vitro. Reproduced with permission of Ref. [222]. Copyright © 2020 American Chemical Society. D Schematic illustration of drug-loaded PDA-HA nanoparticle in combination with chemo-immuno-photothermal therapy. E The corresponding quantification of the number of CD8⁺ T cells and F NK cells. Reproduced with permission of Ref. [160]. The copyright is owned by the author under the Creative Commons Attribution-NonCommercial 3.0 Unported Licence

Fig. 5

Inorganic material-based nano-delivery systems with TCM active ingredients. A Prediction of EGCG-pNG complex assembly. B Serum cytokine levels and C NK cytotoxicity in tumor-bearing mice after treatment. Reproduced with permission of Ref. [179]. Copyright © 2011 Elsevier. D Ginsenoside Rg3-loaded carbon nanotubes suppress the PD-1/PD-L1 pathway in TNBC. Reproduced with permission of ref. [190]. The copyright is owned by the author under the Creative Commons Attribution License. E Schematic representation of synergistic antitumor immunotherapy mechanism of MSN nanoparticles. Reproduced with permission of Ref. [158]. Copyright © 2021 Elsevier

Fig. 6

Biomimetic material-based nano-delivery systems with TCM active ingredients. A Schematic diagram of hyperthermia enhanced chemotherapy and immunotherapy with HSA nanoparticles. Reproduced with permission of Ref. [154]. Copyright © 2022 Wiley–VCH GmbH. B Preparation of hEL-RS17. Reproduced with permission of Ref. [216]. Copyright © 2023 Wiley–VCH GmbH. C Flow cytometry analysis of mature DCs, M2-TAMs, M1-TAMs, CTLs, and Tregs in glioblastoma tissues. Reproduced with permission of Ref. [199]. Copyright © 2023 American Chemical Society