Table 2. Characterization, efficacy and anti-tumor mechanism of nano-TCM monomers.

Nanomaterial	Monomer	Experimental model	Changes in tumor cells and tumor size	Particle size	Zeta potential	Stability	Drug loading ratio (DL%) = or drug loading capacity (LC%)	Encapsulation efficiency	Efficacy	Antitumor Mechanism
Lipsomes	Curcumin	Tumor-bearing mice	Inhibits tumor cell activity and subcutaneous tumor growth	50–100 nm	−25 mV or more	4 °C for 6 months	LC% = Curcumin: total phospholipids = 0.5–1:10	95% or more	Liposomes can encapsulate hydrophilic and hydrophobic drugs, improve the stability, biocompatibility and solubility of traditional Chinese medicine monomers, improve pharmacokinetics and tissue distribution, reduce toxicity, and improve therapeutic index.	Significantly inhibits the growth of subcutaneous tumors in mice and alleviates the progression of metastatic tumors (Park et al., 2023)
	Quercetin	Y79 cell	Reduces tumor volume	108.87 nm	−34.83 mV	4 °C for 5 days	1.26%	96.20%		Increase the internalization of drugs in Y79 cells and increase the killing effect of drugs on tumors (Mao et al., 2021)
	Ginsenoside Rg3	HepG2 and A549 cell	Reduces the rate at which tumors grow in size	133.9 nm	−23 mV			82.47%		Increased the expression of pro-apoptotic protein Bax, and enhanced the toxicity and apoptotic effect of DTX on tumor cells. At the same time, Rg3 inhibited STAT3 activation, reduced tumor cell secretion of CCL2, reduced the recruitment of MDSCs and TAMs in the lungs, destroyed the metastatic microenvironment (Siska et al., 2020)
	Triptolide	HepG2 cell	Enhance uptake of HepG2 cells	119.12 ± 2.78 nm	−16.9 ± 1.2 mV	4 °C for 7 days	LC% = 0.06 ± 0.002%	88.1 ± 1.8%		Celastrol exerts its antitumor effects through mechanisms such as inhibiting cell proliferation, inducing autophagy, and suppressing inflammatory stress. The combined use of the two can exert a synergistic effect by blocking the cell cycle and inducing apoptosis, reducing the drug dose and adverse reactions (Zeng et al., 2023)
	Curcumin	A549 cell	Significantly inhibited the invasion of A549 cells, with a tumor suppression rate of 90.3%	93 nm	+3 mV			95.23%		It has active tumor targeting, which can significantly improve tumor penetration and cellular internalization in the liposome drug delivery system (Gallien et al., 2021)
	Honokiol	A549 cell	Inhibited tumor cell proliferation, tumor inhibition rate of 60.7%	115.7 nm	−18.31 mV	Room temperature for a week				It enters the cell through endocytosis and can escape from lysosomes to improve drug absorption; CLT induces apoptosis, and apoptosis may be manifested by increased intracellular Ca²+ levels through the mitochondrial pathway. CLT can also significantly inhibit the migration and invasion of A549 cells, significantly reduce tumor growth, and increase tumor cell proliferation (Ki67 level decreases) and apoptosis (apoptosis rate increased by TUNEL detection) (Sharma et al., 2019)
	Ginsenoside Rg3	MCF-7cell Mouse breast cancer model	Reduced the production of tumor-associated fibroblasts (TAFs) and collagen fibers, resulting in a tumor inhibition rate of 90.3%	88.7 ± 0.99 nm		37 °C for 72 h	DL% = 20.15%	97.35%		Rg3-PTX-LPs remodel the tumor microenvironment (TME) by inhibiting the IL-6/STAT3/p-STAT3 signaling pathway, repolarizing pro-tumor M2 macrophages to anti-tumor M1, inhibiting the activity of myeloid-derived suppressor cells (MDSCs), and reducing the production of tumor-associated fibroblasts (TAFs) and collagen fibers (Wu et al., 2022)
	Salvianolic acid B	Breast cancer NIH3T3 cell	Reduces the migration and invasion ability of tumor cells, inhibits tumor growth, and reduces tumor weight	166.2 nm	−37.76 mV	4 °C for 15 days	LC% = 17%	82%		Enhance penetration in tumors and reshape tumor microenvironment (Chen et al., 2025)
	Paclitaxel	C6 glioma cell line, C6luc glioma cell line, human cerebral vascular endothelial cell line, HBMEC, orthotopic glioma model	Inhibited the proliferation and migration of C6 cells, induced their apoptosis, significantly inhibited the growth of glioma in situ, and the tumor volume was small.	128.15 ± 1.63 nm	−18.31 mV		DL% = 1.52 ± 0.12%	98.76 ± 0.08%		RVG15 can be modified to bind to nAChR, enhance the uptake of HBMECs and tumor cells, and mediate endocytosis into cells through clathrin. It has a strong ability to penetrate the blood-brain barrier, and can accumulate within the tumor and penetrate deep into the parenchyma; The released PTX exerts a chemotherapeutic effect, inhibits tumor growth and metastasis, and prolongs the survival time of mice (Wu et al., 2022).
	Gambogic acid	4T1 breast cancer cells and human breast cancer cells MDA-MB-231, mouse 4T1 tumor-bearing model	AZGL has inhibitory effect on 4T1 and MDA-MB-231 cells, and the tumor almost disappears.	87.7 ± 9.2nm	−16.9 mV	7 days	DL% = 1.04 ± 0.01%	38.40 ± 0.57%		GA in AZGL nanoparticles can inhibit HSP90 overexpressed under heat stress, re-sensitization photothermal therapy (PTT); TCPP-mediated photodynamic therapy (PDT) produces ROS to kill heat-tolerant tumor cells; The heat generated by PTT can not only kill cancer cells, but also alleviate tumor hypoxia and enhance the PDT effect. In AZGL, tumors can accumulate, and tumors in the AZGL (PDT PTT) group almost disappear, showing good anti-tumor effects (Wang et al., 2023a).
Exosomes	Resveratrol	U251 and LN428 GBM cell lines	Promotes apoptosis	30–200 nm					It has low immunogenicity, strong homologous targeting, and high biocompatibility to evade immune surveillance. Traditional Chinese medicine exerts anti-tumor activity by regulating TAMs in the tumor microenvironment, regulating tumor cell cycle, inducing apoptosis, inhibiting tumor cell proliferation, migration, invasion and microtubule formation through exosomes, and can also inhibit tumor formation and metastasis by inhibiting the secretion of tumor-derived exosomes	U251 cells are sensitive to resveratrol and exhibit growth arrest and apoptosis, while LN428 cells exhibit drug resistance. It was found that the exosomes (U251/N/Exo) secreted by U251 cells could significantly enhance the sensitivity of LN428 cells to resveratrol, while the U251 exosomes (U251/Res/Exo) treated with resveratrol lost this ability. Protein composition in exosomes may play a key role in regulating the sensitivity of GBM cells to resveratrol (Almeida et al., 2020).
	Curcumin	HepG2 cell		30–150 nm						By inactivating the Wnt/β-catenin pathway and autophagy. In addition, lncRNA SNHG29 plays a key mediating role, silencing activates autophagy, increases β-catenin nuclear translocation to inhibit tumor cell malignant phenotype and mouse tumor growth (Zhong et al., 2021).
	Verbascoside	U87 and U251, subcutaneous xenograft model and lung metastasis model	It inhibits the proliferation, migration and invasion of GBM cells, and promotes apoptosis and inhibits tumor growth and metastasis	64.38 nm						VB-treated GBM cells showed significant inhibition of proliferation, increased apoptosis, and decreased migration and invasion. The expression of miR-7-5p in exosomes was up-regulated, and it could be transmitted to recipient cells through exosomes, inhibiting the EGFR/PI3K/Akt signaling pathway. In vivo: In a subcutaneous xenograft model, VB treatment significantly inhibited tumor volume and weight; In the lung metastasis model, VB reduced the number of lung metastases. The expression of miR-7-5p was up-regulated in tumor tissues, while the expression of EGFR, PI3K, p-Akt and other proteins was down-regulated, indicating that VB inhibited tumor growth and metastasis through exosome-mediated miR-7-5p transmission (Wang et al., 2024b).
	Resveratrol	Huh7 cell line and nude mouse subcutaneous xenograft model	Inhibits tumor cell proliferation, migration, and epithelial-mesenchymal transition (EMT), significantly inhibiting tumor volume and weight	30–150 nm						Resveratrol inhibits exosome secretion in Huh7 cells by downregulating Rab27a, and inhibits the proliferation, migration, and epithelial-mesenchymal transition (EMT) of tumor cells through exosome delivery of lncRNA SNHG29. In addition, resveratrol-induced exosomes further inhibit tumor progression by inhibiting autophagy and the Wnt/β-catenin signaling pathway. The signaling pathway proteins involved include the autophagy markers Beclin1, p62, and LC3, as well as GSK-3β, β-catenin, and c-Myc in the Wnt/β-catenin pathway (Negri et al., 2020).
	Steroidal glycoal kaloids from Solanum lyratum	A549 Lung cancer cells and human umbilical vein endothelial cells (HUVECs)	Inhibition of the transformation of HUVECs into tumor-associated endothelial cells (Td-ECs)							In vitro experiments verified the anti-angiogenic activity of these compounds against tumor cells. Exosomes secreted by A549 cells promote the transformation of HUVECs into tumor-associated endothelial cells (Td-ECs), which is significantly inhibited by steroidal glycosalkaloids such as TSGS and SA1. These compounds may interfere with lipid raft function by aggregating cell membrane cholesterol, thereby inhibiting exosome formation and function, and ultimately inhibiting tumor angiogenesis. Signaling pathway proteins involved include VEGFR2 and its downstream signaling molecules (Liu et al., 2021).
Micelles	Baicalin	Hep G2 and Hela cell	Exhibits higher cytotoxicity in A549 cells	15.60 nm	5.26 mV	After 48 h of incubation in PBS, there was no significant change in particle size	LC% = 16.94%,	90.67%.	It is not easily recognized and captured by the endothelial reticular system, can exist stably in the blood for a long time, can achieve passive targeting of tumor sites through EPR effect, can promote intracellular drug accumulation and anti-tumor effects, and can achieve effective drug release at tumor sites through the introduction of stimulus-responsive prodrugs, such as pH-responsive micelles.	Biotin-modified micelles bind to the biotin receptor (SMVT) on the surface of tumor cells, enter cells through receptor-mediated endocytosis, release paclitaxel (PTX) to exert cytotoxicity, and non-cancer cells (HEK293 cells, biotin receptor negative) have low micelle uptake (Wang et al., 2020a).
	Shikonin	CT26 cells (mouse colon cancer cells), H2 tumor-bearing mice	Tumor volume was significantly reduced, and the tumor inhibition rate reached 62.9%	172.1 nm	−20.3 mV	Leave at room temperature for 7 days	LC% = 9.4 ± 0.6%	82.4 ± 4.2%		SK/Siido1-HMS can trigger immunogenic cell death (ICD), promote CRT exposure, increase the proportion of DCs maturation in draining lymph nodes up to 46.9 ± 7.3%, increase the infiltration of CD8 T cells within the tumor, increase intratumoral γ-interferon-γ (IFN-γ) and tumor necrosis factor-α α, TNF-α), reduce the expression level of IDO-1 and the ratio of kynurenine to tryptophan, reduce the frequency of intratumoral infiltrating regulatory T cells (Tregs), and increase antitumor effects compared with free monomers (Tong et al., 2024).
	Emodin	4T1 breast cancer cells	Cell proliferation is inhibited and tumor volume decreases	37.2 ± 1.7 nm,	0.64 ± 0.3 mV	Store at 4 °C for 30 days	LC% = 13.4 ± 0.4%	77.2 ± 2.7%		Polymers induce apoptosis by depleting GSH and increasing ROS levels, activating the intracellular oxidative stress response. In addition, the structure of the polymer is disrupted in the tumor microenvironment, releasing drugs and enhancing the cellular uptake and accumulation of drugs, further improving the anti-tumor effect (Du et al., 2020).
	Camptothecin	SKOV3 ovarian cancer cells	Proliferation is significantly inhibited	121.6 nm	−23.2 ± 0.5 mV	It exhibits good stability in simulated blood circulation (pH 7.4) and tumor cell microenvironment (pH 5.0).	LC% = 12.927 ± 0.880%	85.097 ± 2.936%		Enzyme responsiveness is achieved by cathepsin B-sensitive ALAL peptide, and a positively charged secondary micelle (9-NC/TPC) is formed after cleavage, which promotes lysosomal escape and enters the nucleus with the help of TAT peptide, inhibits topoisomerase I, and induces apoptosis of tumor cells. The micelles increase drug loading through π-π stacking to ensure stable drug delivery, while using the acidic environment and enzyme activity in tumor cells to achieve targeted release, enhancing the cellular uptake and intranuclear accumulation of drugs (Zheng et al., 2020).
	Andrographolide	CT26 colon cancer cells	Improves toxicity to tumor cells	84.68 ± 2.08 nm,	−12.49 ± 2.28 mV	Store at room temperature for 7 days	DL% = 6.84 ± 0.01%	91.15 ± 0.05%		BSP-VES micelles significantly improved the anti-tumor effect of AG by enhancing cell uptake and tumor targeting. In the experiment, the proliferation of CT26 colon cancer cells was significantly inhibited, and the tumor volume was significantly reduced in the in vivo experiment. In addition, BSP-VES micelles improved their toxicity to tumor cells by enhancing the intracellular accumulation of AG while reducing damage to normal cells (Zhao et al., 2012).
	Emodin		Apoptosis is initiated, the tumor volume is reduced by 70%, and it disappears completely after 2 weeks	100 nm		Medium with deionized water and 10% fetal bovine serum for 7 days	LC% = 73.8 ± 2.8%			Iron oxide nanocubes produce local high temperature (42–45 °C) under alternating magnetic field, triggering the upregulation of heat shock protein (HSP) expression, disrupting tumor cell homeostasis and activating the mitochondrial apoptosis pathway, high temperature induces increased cell membrane fluidity, promotes the flow state of the PHEP chain in the micelle core, accelerates the release of the hydrophobic drug emodin, which blocks DNA replication by inhibiting Topoisomerase II activity, and activates the MAPK pathway to induce cell cycle G2/M phase arrest, Magnetic targeting enhances drug accumulation at tumor sites, and local high concentration of emodin further down-regulates the expression of anti-apoptotic protein by inhibiting the NF-κB signaling pathway, and synergizes hyperthermia to induce programmed cell death (Song et al., 2020).
	Shikonin	MDA-MB-231 (Luc1) cell	Significantly inhibits the volume and weight of TNBC tumors	<70 nm		It is well stable at pH 7.4 with 50% fetal bovine serum (FBS).	LC% > 50%			SK inhibits mitochondrial biosynthesis by binding to and inhibiting mitochondrial polymerase γ (POLG), which in turn downregulates the expression of PGC-1α (peroxisome proliferator-activating receptor γ coactivator 1α), inhibiting mitochondrial DNA (mtDNA) levels. This mechanism leads to a decrease in the proliferation and metabolic capacity of tumor cells, ultimately inhibiting tumor growth and metastasis. In the experiment, the expression of POL and PGC-1α in SK-treated TNBC cells and tumor tissues was significantly reduced, and the number of mitochondria and ATP levels in tumor cells were also significantly reduced. In vivo experiments, SK significantly inhibited the volume and weight of TNBC tumors and reduced the number and area of lung metastases (Su et al., 2017).
Carbon nanotubes	Curcumin	4T1 breast cancer cell line	Reduced cell viability	8.5 nm,	−14 eV		DL% = 27.14%,		With a hollow physical structure and easy to modify chemical properties, it can be developed for the delivery of therapeutic drug carriers, enhance the pharmacological activity of traditional TCM monomers, reduce drug side effects, and increase drug accumulation in tumor sites.	The drug release rate of CNT-Pt-CUR in the acidic environment (pH 4.7) was significantly higher than that in the physiological environment (pH 7.4), and it showed good pH sensitivity. In addition, combined with X-ray radiation, CNT-PT-CUR significantly enhanced the killing effect on tumor cells, and it was speculated that it could enhance the radiotherapy effect by increasing the production of reactive oxygen species (ROS), inducing DNA damage and cell cycle arrest (Wang et al., 2020c).
	Plumbagin	Bel-7402 tumor cells HepG-2 for liver cancer and HCT-116 for colon cancer	Significantly reduces the survival rate of tumor cells and induces apoptosis	300 nm		Good stability was shown in water, PBS, and complete media				After PLB-PEG-SWNTs are internalized into cells, the amide and ester bonds that connect drug molecules and SWNTs are hydrolyzed and broken, and the drug molecules are directly released to directly act on the G2/M phase control points of tumor cells and initiate the apoptosis pathway, thereby affecting cell division and proliferation (Li et al., 2021).
	Ginsenoside RG3	TNBC cell	Promotes apoptosis of tumor cells, reducing tumor volume by approximately 65%							Rg3-CNT down-regulates the expression of PD-L1 protein on the surface of tumor cells, blocks its immunosuppressive binding to PD-1 on the surface of T cells, relieves immune escape, and inhibits the transcriptional expression of PD-L1 by inhibiting the mRNA and protein levels of the epiregulatory factor BRD4. Rg3-CNT reduced tumor volume by about 65%, delayed growth by about 18 days, and decreased PD-L1 expression in tumor tissues by 40–50% (Liang et al., 2023).
	Paclitaxel	L929 mouse embryonic fibroblasts and Hela cell lines	Significantly inhibited the growth of Hela cells	65–105 nm		74.4% release rate within 96 h	LC% = 58–77%,	29–36.5%		CNTs-g-PMAA enables targeted therapy of tumor cells through the rapid release of anti-cancer drugs (e.g., paclitaxel, PTX) in an acidic environment. This mechanism exploits the acidic microenvironment of tumor cells (pH 5.8–6.8) in contrast to the normal physiological environment (pH 7.4), allowing for precise drug release, enhancing anti-cancer effects and reducing toxicity to normal cells. PTX-loaded CNTs-g-PMAA had a better inhibitory effect on tumor cells than free PTX in an acidic environment, and had lower toxicity to normal cells (Shao et al., 2015).
Dendrimers	Honokiol	Huh-7 and HepG-2 hepatoma cells	Inhibit tumor cell proliferation and promote tumor cell apoptosis	119.9 to 199.5 nm	−10.9 mV to –22.3	It exhibits good stability in both water and ethanol	DL% = 1.4 to 5.37%	5.37%	The surface functional groups can be covalently coupled to the monomer of traditional TCM, and the drug loading is controllable. It has active targeting, and the end can modify the target molecule (such as RGD peptide) to improve tumor specificity. The positively charged surface promotes cell uptake and has high transmembrane efficiency.	The ability to inhibit MMP-9 is conferred by modification of latent zinc-bound branched linkers and terminals. The synthetic Third - Generation Carboxylic Acid - Terminated Dendrimer (TPG 3-OH) 10) and hydrazide analogue ((TPG 3-NH2) 12) were safer against normal lung fibroblasts than Honokiol. (TPG3-NH₂)12 has better inhibitory activity than (TPG3-OH)10 for MMP-9 and MMP-2 (Mohd Nurazzi et al., 2021).
	Curcumin	Glioblastoma cells	Significantly reduces the activity of tumor cells	4 nm	−32.4 mV ± 0.4	10.1 min	DL% = 10%	85.097 ± 2.936%		G4 90/10-Cys dendritic macromolecule can effectively encapsulate curcumin and significantly reduce the activity of human (U87), murine (GL261), and rat (F98) glioblastoma cells, with less effect on normal cells (e.g., HEK 293, mouse and rat bone marrow mesenchymal stem cells). Encapsulated curcumin significantly improves anti-tumor efficacy by increasing its bioavailability (Mohammadi et al., 2024).
	Conjugated podophyllotoxin	Mouse model of hepatocellular carcinoma (HCC).	Inhibits liver fibrosis and hepatic stellate cell activation				DL% = 9:1			Reduces interleukin-6 (IL-6) levels and inhibits its induced DNA damage and tumor growth; 2) inhibition of the expression of nuclear factor kappa B (NF-κB) and blocking the key link between inflammation and cancer; 3) Reduce the expression of transforming growth factor-β (TGF-β) and α-smooth muscle actin (α-SMA), and inhibit liver fibrosis and hepatic stellate cell activation. Together, these effects inhibit the progression of HCC (Zhong, 2011)
	Resveratrol	Lung cancer A549 cells	Inhibits cell proliferation	251.4 ± 15.7 nm		Store at room temperature for a long time	LC% = 18.4 ± 0.9%	75.1 ± 2.2%		Through ester bond bonding, a large number of drugs are released after complete hydrolysis of ester bonds catalyzed by enzymes in esterase-rich tumor cells, enhancing the anticancer activity of drugs (Zhou et al., 2020)
Nanogels	Emodin	HepG2 hepatocellular carcinoma cell line and a nude mouse subcutaneous xenograft model	Induces apoptosis and reduces tumor volume and weight	80 nm	−24.13 mV at pH 7.4 and 1.21 mV at pH 6.5	Store at 25 °C for 14 days	DL% = 100%		The three-dimensional cross-linked network structure is suitable for loading water-soluble TCM monomers, intelligent response release such as pH/temperature response, tumor microenvironment triggers gel swelling or contraction, release of drugs, has good biocompatibility, degradation products are non-toxic, and the surface can be modified to target ligands (such as folic acid) or immune checkpoint inhibitors (PD-L1 antibodies)	By targeting mitochondria, Rhein−DOX nanogel significantly increases intracellular reactive oxygen species (ROS) levels, decreases mitochondrial membrane potential (ΔΨm), and induces apoptosis. These changes suggest that nanogels exert anti-tumor effects by enhancing ROS-mediated mitochondrial damage and inducing apoptosis. Signaling pathway proteins involved include proteins related to mitochondrial function (e.g., JC-1) and apoptosis-related proteins (e.g., Annexin V) (Singh & Kesharwani, 2021)
MOFs contain ferrous metal-organic frameworks	Triptonide		Activates dendritic cell maturation (DCs) maturation and T cell infiltration	100 nm	−17 mV	Store at 4 °C 30 days	DL% = 36.2%	81.4%	The porous structure can efficiently load hydrophobic TCM monomers and encapsulate chemotherapy drugs at the same time. Fe2+/Fe3+ produces reactive oxygen species (ROS) through the Fenton reaction, which directly kills tumor cells, synergizes with the anti-tumor mechanism of traditional TCM monomers, and has imaging functions.	TPL inhibits Nrf2 expression and interferes with de novo glutathione (GSH) synthesis, increasing cell sensitivity to ferroptosis; At the same time, Fe3+ increased the intracellular ROS level through the Fenton reaction after entering the cell, and the two synergistically amplified the production of ROS and induced ferroptosis, which was manifested by down-regulation of Nrf2 and GPX4 expression and decreased GSH level. On the other hand, TPL can induce GSDME-dependent pyroptosis, and Fe3+ enhances this process by activating caspase-3, causing it to cleave GSDME to produce N fragments, forming pores in the cell membrane, causing cell swelling, membrane rupture, and the release of IL-1β and LDH, etc., to trigger pyroptosis (Sharma et al., 2017)
Self-assembling nanoparticles	Ursolic acid	3T3 cells LNCaP cells	Targeting CAF cells and regulating the tumor microenvironment	195.13 ± 8.06 nm,	−29.07 ± 0.55 mV	Store at 4 °C for 30 days	LC% = 12.93%,	92.80%	The hydrophobic nucleus is loaded with fat-soluble drugs, the hydrophilic shell enhances stability, the photosensitive or redox-sensitive bonds are designed, the targeted modification is convenient, the surface is easy to couple the targeted molecule, and the self-assembly process is simple, which is suitable for industrial scale-up.	Anisamide-modified ursolic acid nanoparticles can significantly down-regulate the expression of NRG1 in CAF cells, thereby reducing the phosphorylation levels of HER3 and AKT in LNCaP cells, thereby alleviating enzalutamide resistance. This mechanism suggests that the nanoparticles modulate signaling pathways in the tumor microenvironment by targeting CAF cells and enhance the sensitivity of prostate cancer cells to enzalutamide (Khalil et al., 2021)