An article by Deng et al. [1] that was first published in ACS Nano in 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.

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Traditional Chinese Medicine
Antitumor applications of nano-traditional Chinese medicine
Jing-Na Zhou1
, Guo-Wei Zhang1
*
1
College of Traditional Chinese Medicine, Hebei University, Baoding 071000, China.
*Corresponding to: Guo-Wei Zhang, College of Traditional Chinese Medicine, Hebei University, No. 342 Yuhua
Road, Baoding 071000, China. E-mail: xxzgw@126.com.
Abbreviations:
CINPs, Cuttlefish ink; TAMs, Tumor-associated macrophages; TCM, Traditional Chinese medicine; MAPK,
Mitogen-activated protein kinase.
Competing interests:
The authors declare that they have no conflict of interest.
Citation:
Jing-Na Zhou, Guo-Wei Zhang. Antitumor applications of nano-traditional Chinese medicine. Traditional
Medicine Research 2019, 4 (5): 224-226.
Executive Editor: Nuo-Xi Pi.
Submitted: 4 August 2019, Accepted: 12 August 2019, Online: 13 August 2019.

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doi: 10.12032/TMR20190813129
TMR | September 2019 | vol. 4 | no. 5 |225
An article by Deng et al. [1] that was first published in
ACS Nano in 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 [Physalis
alkekengi L. var. franchetii (Mast.) Mak] and
Chuanxinlian (Herba Andrographitis), 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 et al.
were the first to propose the concept of “nano-TCM.”
Their study in 1998 found that when Niuhuang
(Calculus Bovis) 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 et al. 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 et al. [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 M1 macrophages 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” (Os Sepiae seu Sepiellae), 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 et al. [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

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instance, Zhang et al. [11-12] have found that the
antitumor effect of nano-paclitaxel was superior to that
of paclitaxel. Moreover, Wen et al. [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 et al. [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.
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