Table 4 DDSs for ginsenoside studied in preclinical cancer models
From: Ginsenosides emerging as both bifunctional drugs and nanocarriers for enhanced antitumor therapies
DDS | Carrier | Bioactive compound | Target form/molecular | Cancer model | Loading efficiency | Encapsulation efficiency | Main results | References |
|---|---|---|---|---|---|---|---|---|
Polymeric NPs | PEG-COOH | Rh2/Rh1 | Passive tumor targeting | A549 cells | NA | NA | In vitro: PEG-Rh1 conjugate showed stronger anticancer activity in human non-small cell lung cancer cell line | [87] |
NA | Rh2/Re | NA | MCF-7 cells | 38%/32% | NA | In vitro: GS-Rh2 showed significant cytotoxicity to MCF-7 cancer cells | [21] | |
DA-OCMC | CK | NA | HepG2 cells | 10.65% ± 1.49% | 42.65% ± 1.24% | In vitro: CK-NPs showed dose-dependent inhibitory effects on HepG2 cells with IC50 values of 23.33 and 16.58 μg/mL | [105] | |
mPEG-b-P (Glu-co-Phe) | 20 (S)-Rg3 | Passive tumor targeting | Colorectal cancer/ mice | 8.90% | 82.40% | In vitro: Drug-loaded NPs possessed longer circulation time in blood In vivo: Proliferation of tumors can be significantly inhibited by Rg3-NPs through reducing expression of proliferating cell nuclear antigen and inducing apoptosis by increasing expression of caspase-3 in subcutaneous colon cancer model in mice | [88] | |
ANG-Rg3-NP | Rg3 | NA | C6 glioma cells | 27.2% ± 1.4% | 80.6% ± 3.0% | In vitro: ANG-Rg3-NPs inhibited the proliferation of C6 glioma cells in a concentration-dependent manner. Angioprep-2 functionalized NPs were easier to cross the BBB and accelerate uptake of NPs by cells | [89] | |
CS/HA /HPC | 20 (R)-Rg3 | NA | A549 cells | 15.87% ± 0.09% | 100.8% ± 6.1% | In vitro: Proliferation of A549 cells can be inhibited effectively by microparticles | [90] | |
Liposomes | ePC | Rg3 | NA | A549 cells/ HepG2 cells/mice | NA | 82.47% ± 0.74% | In vitro: Cytotoxicity of A549 and HepG-2 cells could be enhanced by L-Rg3 In vivo: Cmax and AUC of L-Rg3 were 1.19 × and 1.52 × higher than those of Rg3. Growth rate of BALB/c nude mice inoculated with A549 tumor cells was significantly inhibited by L-Rg3. Besides, Tumor growth can be inhibited by liposome by reducing MVD and enhancing angiogenesis inhibition | [97] |
DSPE-PEG2000 | Rg3 | NA | NA | 7.44% ± 0.08% | 85.24% ± 1.02% | In vitro: Rg3-PEGylated liposomes showed sustained release | [96] | |
DSPE-PEG2000 | Rh2 | NA | A549 cells/mice | 15.3% | 88.2% | In vitro: IC50 values of A549 cells treated with DLT indicated that tumor growth could be inhibited by DLT In vivo: DLT showed stronger antiproliferation and apoptosis effects on xenografted tumors. DDS was safer than cisplatin in treatment of tumors | [98] | |
mPEG-PLA | Rh2 | Passive tumor targeting | HepG2/mice | NA | 94.93% ± 4.18% | In vivo: Fluorescence intensity at tumor site decreased gradually after injection of PLP for 8 h and lasted for 24 h. Rh2-PLP was superior to Rh2-LP and Rh2-CLP in anti-tumor effect | [100] | |
EYPC/Rh2 /Rg3/Rg5 | PTX/Rh2/Rg3 /Rg5 | Active targeting: Rh2/Rg3/Rg5 | BGC-823 cells/mice | Rh2: 5.6% ± 0.3% Rg3: 7.3% ± 0.4% Rg5: 4% ± 0.1% | Rh2: 91.3% ± 2.1% Rg3: 95.5% ± 3.3% Rg5: 82.8% ± 1.6% | In vitro: Ginsenoside liposome can be accumulated in tumor for recognizing GLUT carrier on tumor cell membrane In vivo: Ginsenosides showed significant synergistic effects with PTX for antitumor activity | [26] | |
EYPC/Rh2 | PTX/Rh2 | Active targeting: Rh2 | 4T1 cells /mice | 5.6% | 91.3% | In vitro: PTX-Rh2-liposome showed ~ 80% cell apoptosis to 4T1 cells In vivo: PTX-Rh2-liposome reduced tumor growth to certain extent comparable with lipisu | [25] | |
EPC/Rg3 | PTX/Rg3 | Active targeting: Rg3 | C6 murine glioma cells/mice | 9.80% ± 0.13% | 94.15% ± 1.34% | In vitro: Rg3-liposome promoted C6 glioma cell’s uptake efficiency and tumor penetration simultaneously In vivo: PTX-Rg3-liposome showed antiproliferation effects. Immune microenvironment in glioma was activated, with promoting T cell immune response | [28] | |
Lecithin/Rg5 | PTX/Rg5 | Active targeting: Rg5 | HGC-27 /MCF-7 /A549 cells | NA | 97.20% | In vivo: G-PTX achieved curative effects through targeting GLUT receptor on tumor surface In vivo: Broad-spectrum targeting ability of G-PTX was confirmed with HGC-27, A549, and MCF-7 subcutaneous tumor models, through clathrin and caveolae-dependent pathways for endocytosis | [27] | |
DSPE-PEG2000-tLyp-1 | CK | Active targeting: tLyp-1 peptide | A549 cells/mice | 14.80% | 83.40% | In vitro: tLyp-1 liposomes induced mitochondrial apoptosis of A549 tumor cells against tumor In vivo: tLyp-1 liposomes showed stronger antitumor effect and fewer side-effects on normal tissues than drug combinations | [101] | |
Micelles | pNP-PEG-pNP | Rh2 | NA | A549 cells | NA | 85.23% ± 4.38% | In vitro: CG-M showed stronger cell uptake ability, apoptosis induction ability and antiproliferation activity of A549 cells | [113] |
Solutol HS15/TPGS | Rh2 | NA | A549 cells | 7.68% ± 1.34% | 95.27% ± 1.26% | In vitro: Rh2-M synthesized with Solutol HS15 and TPGS were capable of enhancing solubility and antitumor effects of Rh2 In vivo: Rh2-M displayed a higher tumor inhibition rate in tumor-bearing nude mice | [112] | |
TPGS/PEG-PCL | CK | Passive tumor targeting | A549 and PC-9 cells/ mice | 11.19% ± 0.87% | 94.60% ± 1.45% | In vitro: Growth of A549 and PC-9 cells could be inhibited by CK-M by blocking G1 phase. Bax and Bcl-2 were regulated to promote tumor cell apoptosis and inhibit tumor cell invasion, metastasis, and outflow In vivo: CK-M micelles showed higher tumor inhibition and longer maintenance time of micelles in tumor tissue | [106] | |
PC/DP | CK | Passive tumor targeting | A549 cells/ mice | 11.76% ± 1.32% | NA | In vitro: Micelles exerted proapoptotic effects and antitumor efficacy against human lung carcinoma A549 cells In vivo: Micelles exhibited higher tumor inhibition than free CK through increased permeability and retention effects | [107] | |
DA-OCMC /A54 peptide | CK | Active targeting: peptide A54 | HepG2/Huh-7 cells | 3.18% ± 1.49% | 76.56% | In vitro: Cytotoxicity of APD-CK micelles to HepG2 and Huh-7 cells was significantly higher than that of free CK. APD-CK micelles could promote protein expression of caspase-3, caspase-9, and poly (ADP-ribose) polymerase | [108] | |
AP/TPGS | CK | Passive tumor targeting | A549 cells/mice | 13.26% ± 1.89% | 91.34% ± 5.24% | In vitro: Mixed micelles induced cell apoptosis and inhibited cell migration by inducing cell cycle arrest in the G0/G1 phase of A549 cells In vivo: A549 lung cancer xenografts in mice showed that mixed micelles were an efficient tumor-targeting DDS with obvious antitumor effects | [109] | |
MEs | PLA | 20 (R)-Rg3 | NA | NA | 0.2853 | 0.78 | In vitro: Ginsenoside Rg3 PLA microspheres exhibited controlled release of drugs | [104] |
PLGA | ac-Rb1 | NA | NA | NA | 0.96 | In vitro: Controlled release of ac-Rb1 followed the Fickian diffusion | [102] | |
Etoposide, coix seed oil | Rh2 | NA | A549 cells/mice | NA | 0.9 | In vitro: Cytotoxicity and apoptosis induced by ECG-MEs were significantly enhanced in A549 cells In vivo: Oral ECG-MEs could enter blood circulation through intestinal barrier, then prolonged blood circulation time and accumulated in tumor site. Mechanism of antitumor effect was related to small-scale mediated tumor penetration depth and increased serum Th1 cytokine concentration | [122] | |
Protein-based nanocarriers | BSA | Rg5 | Active targeting: FA | A549 cells/mice | 12.64% ± 4.02% | 73.59% ± 5.50% | In vitro: EPR effect and receptor-mediated targeting led to MCF-7 cell apoptosis In vivo: FA-modified targeted NPs efficiently accumulated Rg5 within 8 h at tumor site in MCF-7 xenograft mouse model, showing strong tumor aggregation capacity | [118] |
BSA | Rh2 | NA | A549/HT29 cells | 0.36Â mg of Rh2/mg of BSA-Rh2 NPs | NA | In vitro: BSA-CK NPs had stronger inhibitory effects on lung cancer A549, HepG2 hepatoma, and HT29 colon cancer cell lines | [115] | |
GNPs | DCY51T-AuCKNps | CK | NA | A549/HT29 cells | 11.03% | NA | In vitro: DCY51T-AuCKNp showed enhanced cell apoptosis in A549, HT29, and AGS cells, suggesting that DCY51T-AuCKNp was an effective photothermal agent with synergistic chemotherapy effects | [110] |
Carbon nanomaterials | CDs | Re | NA | MCF-7/HepG2/A375 | NA | NA | In vitro: Small-sized Re-CDs were beneficial to cellular uptake, which had strong fluorescence imaging properties. Re-CDs could inhibit tumor cell proliferation through ROS-mediated pathway | [117] |
CNTs | Rb1/Rg1 | NA | MCF-7/PANC-1 cells | NA | NA | In vitro: Induction effect on MCF-7 and PANC-1 cell death pathway of ginsenoside CNT was stronger than pure ginsenoside | [103] | |
GO | Rh2 | NA | OVCAR3/MDA-MB/A375 cells | NA | NA | In vitro: Rh2, amino acid Lys and Arg modified GO showed higher antitumor activity and lowest toxicity to coagulation system and heart tissue | [116] | |
MSNPs | MSNPs | CK/Rh2 | NA | A549/HepG2/HT-29 cells | NA | NA | In vitro: MSNPs enhanced efficacy of CK and Rh2, exerting anticancer effects on HepG2, A549 and HT-29 colon cancer cells | [111] |