Antitumor applications of nano-traditional Chinese medicine

Jing-Na Zhou, Guo-Wei Zhang*

Antitumor applications of nano-traditional Chinese medicine

Jing-Na Zhou1, Guo-Wei Zhang1*

1College of Traditional Chinese Medicine, Hebei University, Baoding 071000, China.

An article by Deng[1] that was first published inin 2019 revealed that nanoparticles extracted from cuttlefish ink (CINPs) could inhibit tumor growth by synergizing immunotherapy and photothermal therapy. The researchers found that these CINPs, which had significant antitumor efficacy, could effectively reprogram tumor-associated macrophages (TAMs) from the immune-suppressive M2-like phenotype to the antitumor M1-like phenotype.

There were reportedly approximately 18.1 million new cancer cases and 9.6 million cancer-related deaths in 2018 worldwide [2]. As of 2015, the mortality rate from malignant tumors accounted for 23.91% of all causes of death in China, and this rate is still on the rise [3]. The pathogenesis of human tumors is the result of multiple factors jointly influencing gene expression, which implies that these tumors have low controllability. Hence, it is a topic of wide concern in clinical settings.

Surgery, radiotherapy, chemotherapy, and molecular targeted therapy are currently the main approaches for treating tumors. Among them, surgery and radiotherapy are localized treatments, whereas chemotherapy and molecular targeted therapy are systemic treatments. A number of traditional Chinese medicine (TCM), such as Jinyinhua [()] and Chuanxinlian (), have been found to exert antitumor effects, most of which are achieved by regulating the overall immune abilities of the body. However, the traditional dosage forms and modes of administration have numerous problems, such as a slow onset and long administration cycles, hindering their effective application in clinical settings. With the increasing recognition of TCM, especially since the recent discovery of antitumor substances extracted from TCM (e.g., paclitaxel and camptothecin), extensive studies have been conducted on their antitumor effects and applications. Recently, the application of nanotechnology in biomedicine has become a topic of great interest [4]. Owing to the good biocompatibility of nanoparticles, they have been widely used in the development of delivery systems for new drugs [5].

Nano-TCM is a frontier technological field that has undergone rapid development in recent years. Its main focus is currently on the following two aspects: (1) research on TCM nanoparticles, (2) research on the combination of nanocarriers and TCM [6]. Xu. were the first to propose the concept of “nano-TCM.” Their study in 1998 found that when Niuhuang () was processed to the nanoscale level, there were significant changes in its physical and chemical properties, which resulted in enhanced therapeutic efficacy and certain targeted effects. Nano-realgar is one of the TCM that have been most extensively studied. Studies into its antitumor effects have already included its antitumor mechanisms, safety evaluation, and in vitro and in vivo experiments [7] and shown that it has good prospects in clinical applications. In addition, many scholars have begun to extract certain components in TCM for antitumor research. For instance, Zhu. conducted a nanotechnological study on polysaccharide components in TCM [8]. They found that polysaccharides with different bioactivities showed significantly enhanced biological functions, especially immunomodulatory functions, after being bound to nanoparticles, and hence demonstrated good developmental prospect for their antitumor effects.

The latest discovery by Deng[1] demonstrated that CINPs could effectively reprogram TAMs from the immune-suppressive M2-like phenotype to the antitumor M1-like phenotype, mainly through the activation of the mitogen-activated protein kinase (MAPK) signaling pathway. These CINPs have a spherical morphology, and good dispersibility and biocompatibility; are rich in melanin; and contain a variety of amino acids and monosaccharides. Furthermore, the researchers also found that the CINPs showed high photothermal effects and tumor killing ability under near-infrared irradiation, thereby enabling them to effectively synergize with tumor photothermal therapy. Moreover, the CINPs increased the proportion of M1macrophages and promoted the recruitment of cytotoxic T lymphocytes in vivo, thereby reducing primary tumor growth and lung metastasis. Therefore, when combined with their photothermal effects, the CINPs induced the release of tumor-specific antigens, almost completely inhibiting tumor growth while also triggering more active immune responses. In addition, the researchers studied the stability and safety of CINPs. Their results indicated that the CINPs had good stability, high biocompatibility, and minimal systemic toxicity, demonstrating their excellent prospects in clinical application.

Cuttlefish is the original source of the TCM “Haipiaoxiao” (), an astringent formula that has the effects of arresting spontaneous emissions and discharge, exerting astringency and hemostasis, and eliminating dampness and astringing sores [9]. Modern pharmacological studies have shown that its effects include the neutralization of gastric acid, protection of mucous membranes, treatment of ulcers, reduction of phosphorous, and promotion of hemostasis and osteogenesis [10]. Furthermore, the latest study has shown that it also exhibits antitumor effects. If we combine this with the study conducted by Deng. [1], we could perhaps venture to propose the following interesting speculation: for any TCM that has been pharmacologically shown to have antitumor effects, its nanoparticles or nanoparticles composed of its specific components will have even greater antitumor effects, which can be synergized with conventional antitumor treatment to inhibit tumor growth. This speculation is not without its basis. For instance, Zhang[11-12] have found that the antitumor effect of nano-paclitaxel was superior to that of paclitaxel. Moreover, Wen[13-14] conducted an experimental study on the antitumor effects of freeze-dried hydroxycamptothecin powder for injection and a hydroxycamptothecin nano-formulation, and found that the effects of the nano-formulation was superior to those of the freeze-dried powder.

In summary, the latest study by Deng[1] included an in vivo experiment on animals that demonstrated the safety and reliability of the CINPs, indicating their excellent prospects for clinical application. In addition, this latest study also provides some ideas for conducting antitumor research on other TCM. We believe that there are good prospects for the clinical application of nano-TCM, especially in the field of antitumor nano-TCM.

1. Deng RH, Zou MZ, Zheng DW,Nanoparticles from Cuttlefish Ink Inhibit Tumor Growth by Synergizing Immunotherapy and Photothermal Therapy. ACS nano 2019.

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4. Ye X, He X, Lei Y,One-pot synthesized Cu/Au/Pt trimetallic nanoparticles with enhanced catalytic and plasmonic properties as a universal platform for biosensing and cancer theranostics. Chem Comm 2019, 55: 2321-2324.

5. Wang YH, Song XM, Jiang Y,Methodological study on in situ target identification of active constituents of traditional Chinese medicine based on magnetic nanoparticle carrier. Chin J Chin mater med 2019, 44: 2657-2661. (Chinese)

6. Kou ZY, Wang SF, Zhou G. Research and prospect of nano-Chinese medicine. Jilin Normal Univ J (Natur Sci) 2005: 31-32. (Chinese)

7. Li HJ, Qi YF, Li XR. Study on anti-tumor research of nano-realgar. Liaoning J Tradit Chin Med 2018, 45: 105-107. (Chinese)

8. Zhu N, Zhang LS, Wang FJ. Nanotechnology application of active ingredients of traditional Chinese medicine polysaccharides. Chin J New Drug 2017, 26: 60-65. (Chinese)

9. Wang D, Wang JJ. Modern research progress in the hemostasis of Chinese medicine Haipiaoxiao (cuttlefish bone). Acta Chin Med Pharmacol, 2018, 46: 113-118. (Chinese)

10. Fang YQ, Zhao YH. Research Progress of cuttlebone. Chin J Ethnomed Ethnopharm 2016, 25: 47-48. (Chinese)

11. Zhang YY, Zhang XY, Fu XD,. Inhibitory effect of paclitaxel tumor targeted delivery system on MCF-7 cells. J Zhengzhou Univ Med Sci 2013, 48: 595-598. (Chinese)

12. Zhang YY, Fu XD, Liu KD,Preparation and targeting of NGR-single-wall carbon nanotube-paclitaxel complex. Chin Pharm J 2013, 48: 1748-1754. (Chinese)

13. Wen LJ. Tissue distribution of hydroxycamptothecin lyophilized powder needle and nano-preparation in mice with liver tumor in situ. Northwest Pharm J 2011, 26: 40-43. (Chinese)

14. Wen LJ. Study on pharmacodynamics of hydroxycamptothecin nano-preparation on mice with liver tumor in situ. Chin J New Drugs Clin Remed 2012 31:100-103. (Chinese)

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CINPs, Cuttlefish ink; TAMs, Tumor-associated macrophages; TCM, Traditional Chinese medicine; MAPK, Mitogen-activated protein kinase.

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The authors declare that they have no conflict of interest.

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Jing-Na Zhou, Guo-Wei Zhang. Antitumor applications of nano-traditional Chinese medicine. Traditional Medicine Research 2019, 4 (5): 224-226.

:Nuo-Xi Pi.

:4 August 2019,

12 August 2019,

:13 August 2019.

10.12032/TMR20190813129

Guo-Wei Zhang, College of Traditional Chinese Medicine, Hebei University, No. 342 Yuhua Road, Baoding 071000, China. E-mail:xxzgw@126.com.