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Review
. 2024 Mar 12:19:2507-2528.
doi: 10.2147/IJN.S455407. eCollection 2024.

Exploiting Nanotechnology for Drug Delivery: Advancing the Anti-Cancer Effects of Autophagy-Modulating Compounds in Traditional Chinese Medicine

Zixian Liu  1 , Tianming Lu  1 , Ruoning Qian  1 , Zian Wang  1 , Ruogu Qi  1 , Zhengguang Zhang  1
Affiliations
Review

Exploiting Nanotechnology for Drug Delivery: Advancing the Anti-Cancer Effects of Autophagy-Modulating Compounds in Traditional Chinese Medicine

Zixian Liu et al. Int J Nanomedicine. .

Abstract

Background: Cancer continues to be a prominent issue in the field of medicine, as demonstrated by recent studies emphasizing the significant role of autophagy in the development of cancer. Traditional Chinese Medicine (TCM) provides a variety of anti-tumor agents capable of regulating autophagy. However, the clinical application of autophagy-modulating compounds derived from TCM is impeded by their restricted water solubility and bioavailability. To overcome this challenge, the utilization of nanotechnology has been suggested as a potential solution. Nonetheless, the current body of literature on nanoparticles delivering TCM-derived autophagy-modulating anti-tumor compounds for cancer treatment is limited, lacking comprehensive summaries and detailed descriptions.

Methods: Up to November 2023, a comprehensive research study was conducted to gather relevant data using a variety of databases, including PubMed, ScienceDirect, Springer Link, Web of Science, and CNKI. The keywords utilized in this investigation included "autophagy", "nanoparticles", "traditional Chinese medicine" and "anticancer".

Results: This review provides a comprehensive analysis of the potential of nanotechnology in overcoming delivery challenges and enhancing the anti-cancer properties of autophagy-modulating compounds in TCM. The evaluation is based on a synthesis of different classes of autophagy-modulating compounds in TCM, their mechanisms of action in cancer treatment, and their potential benefits as reported in various scholarly sources. The findings indicate that nanotechnology shows potential in enhancing the availability of autophagy-modulating agents in TCM, thereby opening up a plethora of potential therapeutic avenues.

Conclusion: Nanotechnology has the potential to enhance the anti-tumor efficacy of autophagy-modulating compounds in traditional TCM, through regulation of autophagy.

Keywords: anti-cancer; autophagy; nano-delivery; traditional Chinese medicine.

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Conflict of interest statement

The authors declare no competing interests in this work.

Figures

Figure 1
Figure 1
Application of nanoformulations in cancer therapy (diagram by Figdraw ID:USYUWa2b9d). Multifunctional nanoformulations, encompassing nanoparticles, nano micelles, metal-on-framework (MOF) nanoparticles, liposomes, and biomimetic nanoparticles, improve the solubility and biocompatibility of free drug, overcoming delivery barriers, which further provide better anti-cancer effects via targeted delivery, controlled release, drug synergy, and combined therapy.
Figure 2
Figure 2
Crosstalk between autophagy and other types of cell death ways (diagram by Figdraw ID: UAIYY17111). There is an intricate interplay of signaling pathways between autophagy and apoptosis, necroptosis, ferroptosis, and ICD, potentially influencing cancer therapy outcomes. Common regulatory molecules are shared between autophagy and other cell death pathways, indicating a complex regulatory relationship between autophagy and multiple cell death pathways.
Figure 3
Figure 3
The autophagic process and mechanism (diagram by Figdraw ID:OURUO90494). Autophagy is a highly regulated cellular process involving initiation, nucleation, elongation, fusion, and degradation, which is governed by a sophisticated network of genes and proteins. Key components of autophagy include ATG, LC3, and p62 proteins, with alterations in the levels of LC3 serving as a reliable indicator of autophagic activity.
Figure 4
Figure 4
Autophagic activity depicted by compounds from TCM-loaded NPs in cancer. (A) Enhanced expression of autophagic proteins LC3-II and SQSTM1/p62 was observed in lung and colorectal cancer cells after treatment with Nab-PTX in Western blots and immunofluorescence. Reprinted from Lin YW, Lin TT, Chen CH, et al. Enhancing Efficacy of Albumin-Bound Paclitaxel for Human Lung and Colorectal Cancers through Autophagy Receptor Sequestosome 1 (SQSTM1)/p62-Mediated Nanodrug Delivery and Cancer therapy. ACS Nano. Oct 10 2023;17 (19):19,033–1905. Copyright 2023 American Chemical Society. (B) Nicotinic, curcumin, and their nanoparticles regulate expressions of autophagy-related genes (ATG7, Beclin1, mTOR, and p62) and promote autophagosomes formation. The data are shown as the means ± SD (n = 3). * p ≤ 0.05, **p ≤ 0.01, *** p ≤ 0.001 and **** p ≤ 0.0001. Reprinted from Int J Biol Macromol. Volume: 245. Hanafy NAN, Sheashaa RF, Moussa EA, Mahfouz ME. Potential of curcumin and niacin-loaded targeted chitosan-coated liposomes to activate autophagy in hepatocellular carcinoma cells: An in vitro evaluation in HePG2 cell line. 125,572. Copyright 2023, with permission from Elsevier.
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