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Review
. 2023 Aug 8;28(16):5955.
doi: 10.3390/molecules28165955.

Smart Targeted Delivery Systems for Enhancing Antitumor Therapy of Active Ingredients in Traditional Chinese Medicine

Chenglong Kang  1 , Jianwen Wang  1 , Ruotong Li  1 , Jianing Gong  1 , Kuanrong Wang  2 , Yuxin Wang  1 , Zhenghua Wang  3 , Ruzhe He  3 , Fengyun Li  1
Affiliations
Review

Smart Targeted Delivery Systems for Enhancing Antitumor Therapy of Active Ingredients in Traditional Chinese Medicine

Chenglong Kang et al. Molecules. .

Abstract

As a therapeutic tool inherited for thousands of years, traditional Chinese medicine (TCM) exhibits superiority in tumor therapy. The antitumor active components of TCM not only have multi-target treatment modes but can also synergistically interfere with tumor growth compared to traditional chemotherapeutics. However, most antitumor active components of TCM have the characteristics of poor solubility, high toxicity, and side effects, which are often limited in clinical application. In recent years, delivering the antitumor active components of TCM by nanosystems has been a promising field. The advantages of nano-delivery systems include improved water solubility, targeting efficiency, enhanced stability in vivo, and controlled release drugs, which can achieve higher drug-delivery efficiency and bioavailability. According to the method of drug loading on nanocarriers, nano-delivery systems can be categorized into two types, including physically encapsulated nanoplatforms and chemically coupled drug-delivery platforms. In this review, two nano-delivery approaches are considered, namely physical encapsulation and chemical coupling, both commonly used to deliver antitumor active components of TCM, and we summarized the advantages and limitations of different types of nano-delivery systems. Meanwhile, the clinical applications and potential toxicity of nano-delivery systems and the future development and challenges of these nano-delivery systems are also discussed, aiming to lay the foundation for the development and practical application of nano-delivery systems of TCM in clinical settings.

Keywords: antitumor active ingredients; chemical coupling; nano-delivery systems; pharmacological efficacy; physical encapsulation; traditional Chinese medicine.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The application of active components of traditional Chinese medicine in biomedicine.
Figure 2
Figure 2
The timeline of main developments of nano-delivery system. Adapted with permission from Ref. [12]. Copyright 2016, Springer Nature.
Figure 3
Figure 3
(A) Model diagram of programmed drug release. (B) Morphology of 4T1 cells with different treatments. The scale bar is 25 μm. (C) MTT assay results of mice breast cancer cells treated with different protocols. (D) Tumor growth curves of mice after using different treatment regimens. (* p < 0.05, ** p < 0.01, *** p < 0.001). Adapted with permission from Ref. [116]. Copyright 2019, Wiley-VCH.
Figure 4
Figure 4
(A) Schematic overview of the preparation and application of multifunctional microgels for precisely targeted delivery of GA. (B) The apoptosis of HepG2 cells induced by different groups was analyzed by Annexin V-FITC/PI staining. (C) Confocal laser scanning microscope (CLSM) images of live/dead cell staining assay in different groups. (D) The cytotoxicity of HepG2 cells exposed to various concentrations of different groups (GA dosage: 0, 0.5, 1, 1.5, 2, 3, and 4 μg/mL) for 24 h. Data are presented as mean ± SD (n = 3). * p < 0.05, ** p < 0.01, *** p < 0.001. Adapted with permission from Ref. [122]. Copyright 2023, American Chemical Society.
Figure 5
Figure 5
(A) Diagram of the mechanism of action of siRNA@M-/PTX-CA-OMV. (B) In vivo imaging of 4T1 tumor xenografts mice 14 days after administration. (C) Histological images of 4T1 tumor xenografts. Caspase 3: Apoptotic tumor cells. Ki67: Growing tumor cells (scale bar = 100 μm). Adapted with permission from Ref. [136]. Copyright 2021, American Chemical Society.
Figure 6
Figure 6
(A) Diagram of the therapeutic mechanism of nanoparticles (B) H&E-stained sections of lungs. (Scale bars: left: = 100 μm; right: = 50 μm). (C) Effect of esterase and GSH depletion on the degree of intracellular dissociation of both delivery systems (Scale bar: 50 μm). (D) Changes in tumor volume in mice after treatment using different protocols. ** p < 0.01, *** p < 0.001. Adapted with permission from Ref. [141]. Copyright 2020, American Chemical Society.
Figure 7
Figure 7
(A) Illustration of MCA treatment mechanism. (B) Fluorescence images of 4T1 cancer cells incubated with MOF NPs or MCA nanoamplifier under US actuation and then stained with the ROS/hypoxia detection probe: (I) ROS (II) Hypoxia level Scale (bar: 200 µm). (C) H&E staining of liver tissue on days 0, 4, 8, 12, and 16. (T: Tumor NT: Non-tumor). Adapted with permission from Ref. [147]. Copyright 2022, American Chemical Society.
Figure 8
Figure 8
(A) Diagram of the mechanism of immune activation by NPs. (B,C) Expression of p-STING and infiltration of immune cells in tumors; histograms of DC cell and interferon distribution in different protocols (** p < 0.01, *** p < 0.001). (D) CLSM plots of tumor sections from mice. (E) auantification of apoptosis via FCM on CT26 cells treated with Cis, CPT-Pt (IV), Cis + CPT-11 and NPs (10 μM Pt, 20 μM CPT-11) at 24 h. Adapted with permission from Ref. [149]. Copyright 2022, the authors.
Figure 9
Figure 9
(A) Diagrammatic representation of the role of MCPP in tumor cells. (B) Co-localization of MCPP and lysosomes in CT 26 cells. (C) Schematic illustration of pyroptosis induced by MCPP+L. (D) Tumor growth curves for each group (n = 6). *** p < 0.001. Adapted with permission from Ref. [154]. Copyright 2021, the authors.
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