Table 3.
Summary of nanoformulation curcumin and chemotherapeutic drugs in vivo.
| Types of Cancer | Co-Delivery System | Treatment | Animal Model | Findings | References |
|---|---|---|---|---|---|
| Lung cancer | Methoxy poly(ethylene glycol)-poly(caprolactone) (MPEG-PCL) micelles | Curcumin and doxorubicin (5 mg/kg) intravenous tail injection every 5 days until the control mice became weak | The female C57 mice (aged 6-8 weeks) (n = 40) mice were injected subcutaneously with 100 µL of LL/2 cell suspension (1 × 106) into the right flank. The tumor-bearing mice were randomly divided when the mean tumor diameter reached about 6 mm |
1. Tumors in the groups treated with curcumin and doxorubicin/MPEG-PCL were smaller than those receiving the other treatments (p < 0.05) 2. Inhibited the growth of subcutaneous LL/2 lung carcinoma (p < 0.05) 3. Induced apoptosis of tumor tissue and inhibited tumor angiogenesis, as shown in TUNEL assay and CD31 staining (p < 0.05) |
[93] |
| Liver cancer | Lipid nanoparticle | Curcumin and doxorubicin (2 mg/kg doxorubicin) for 20 weeks, intravenously injected once a week |
Diethylnitrosamine-induced hepatocellular carcinoma mice (n = 32) 24 mice were administrated by oral administration of diethylnitrosamine solution in sesame oil (0.1 g/mL) at 40 mg/kg once a week for 15 weeks. 8 mice were administrated with sesame oil only (normal mice) |
1. The liver/body weight (p < 0.05) and serum ALT and AST levels (p < 0.01) were significantly decreased in curcumin and doxorubicin-lipid nanoparticle group 2. The mRNA and protein levels of Bax/Bcl-2 (p < 0.01) were all increased in tumor tissue from curcumin and doxorubicin-lipid nanoparticle group compared to the doxorubicin-lipid nanoparticle group 3. The immunohistochemistry analysis induced expression of caspase-3 4. The expression of c-myc and PCNA decreased significantly in curcumin and doxorubicin-lipid nanoparticle (p < 0.01) compared to the control group 5. The mRNA and protein levels of VEGF in curcumin and doxorubicin-lipid nanoparticle were significantly decreased compared to the control group (p < 0.05) 6. The mRNA levels of MDR1 and Bcl-2, as well as the protein levels of P-gp and Bcl-2 were all decreased in curcumin and doxorubicin-lipid nanoparticle group compared to the doxorubicin-lipid nanoparticle group (p < 0.01) |
[136] |
| Breast cancer | Polymeric micelles | Curcumin (10 mg/kg) and doxorubicin (10 mg/kg) for 12 days | The female BALB/c mice (n = 60) were injected with 1 × 106 4T1 cells into the right axilla of mice. When the tumor reached about 100 mm3, 4T1 tumor-bearing mice were randomly divided into 6 groups (n = 10) | 1. Curcumin and doxorubicin polymeric micelles treated group exhibited a considerable tumor inhibition compared to the saline-treated group (p < 0.001) 2. The AST, LDH, CK, and CKMB were significantly reduced compared to the mice treated with doxorubicin polymeric micelles (p < 0.05) 3. No pathological damages were found in heart, liver, spleen, lung, and kidney in the mice treated with curcumin and doxorubicin polymeric micelles by using H&E staining 4. Tumors treated with curcumin and doxorubicin polymeric micelles had enhanced dark brown spots by using TUNEL assay, indicating that drug encapsulated in micelles could enhance tumor cell apoptosis and showed better antitumor effects |
[123] |
| Breast cancer | Transferrin-poly(ethylene glycol) | Curcumin (50 mg/kg) and doxorubicin (50 mg/kg) were injected into the mice by tail vein for 7 weeks | BALB/c mice were inoculated subcutaneously with 1 × 106 MCF-7 cells. MCF-7 tumor xenografts were grown in BALB/c mice and estrogen was provided as a β-estradiol pellet 1 week prior to the injection of the cells. The tumors were allowed to develop on the posterolateral side of the mice for 1 week prior to treatment to obtain the breast cancer-bearing animal model. The mice were randomly divided into 6 groups | Compared with curcumin and doxorubicin, transferrin-poly(ethylene glycol)-curcumin/doxorubicin nanoparticles presented a remarkably higher inhibition effect towards tumor growth (p < 0.05) | [131] |
| Liver cancer | Biotin-/lactobionic acid–modified poly(ethylene glycol)-poly(lactic-co-glycolic acid)-poly(ethylene glycol) (BLPP) copolymer | Curcumin (10 mg/kg) and 5-FU (4 mg/kg). The mice were injected once at an interval of 2 days of a total of 4 injections through the tail vein for 30 days | The BALB/c nude mice (n = 18) were inoculated subcutaneously with HepG2 cells (2 × 106). The mice were randomly divided into 6 groups (n = 3) when the tumor volume reached about 50 mm3 | 1. The tumors in BLPP/curcumin +5-FU nanoparticle were approximately 8 times smaller than the tumor volume observed in the control (phosphate-buffered saline) group (p < 0.001) 2. The mice treated with BLPP/curcumin +5-FU nanoparticles induced tumor apoptosis or necrosis significantly compared to the BLPP/curcumin nanoparticle (p < 0.05) 3. The western blotting analysis showed that BLPP/curcumin + 5-FU nanoparticle significantly decreases the DPYD expression compared to the BLPP/5-FU nanoparticle and the control groups (p < 0.05) 4. p53 protein expression was higher in BLPP/curcumin groups than in BLPP/5-FU nanoparticle group (p < 0.05) 5. Bcl-2 protein expression of BLPP/curcumin + 5-FU was lower than that of the BLPP/5-FU nanoparticle, BLPP/curcumin nanoparticle, and control groups; while the expression of cytochrome c was higher (p < 0.05) |
[134] |
| Pancreatic cancer | Superparamagnetic iron oxide nanoparticle (SPION) formulation of curcumin (SP-CUR) | 2 treatments groups [Curcumin (100 µg dissolved in 100 μL of 0.1% Tween 20) and gemcitabine (300 μg dissolved in 50 μL of phosphate-buffered saline)] and another two groups were treated with an intraperitoneal injection of 100 μg curcumin loaded SP-CUR and combination with gemcitabine, respectively. Treatments were administered twice weekly for 7 weeks | HPAF-II cells (1.0 × 106) and human pancreatic stromal cells (stromal component; 0.5 × 106) were suspended in 50 μL of HBSS media containing 1% (v/v) matrigel and injected into the parenchyma of the pancreas in old male athymic nude mice (6 weeks old). Five days later, mice were randomly divided into five groups (n = 8) | 1. The bioluminescence imaging results showed a significant (p < 0.05) decrease in the pancreatic tumor volume of SP-CUR + gemcitabine-treated mice compared to the vehicle-treated mice 2. SP-CUR + gemcitabine-treated mice showed a significant decrease in the tumor weight of pancreas compared to the gemcitabine alone (p < 0.0001) 3. None of the mice treated with SP-CUR + gemcitabine were recorded for distant metastasis 4. Immunoblotting and immunohistochemistry analyses showed that SP-CUR + gemcitabine inhibited SHH, NF-қB, Gli-1 and Gli-2 expression 5. SP-CUR + gemcitabine reduced the amount of α-SMA, N-cadherin, and SMO and upregulated hCNT |
[135] |
α-SMA: alpha-smooth muscle actin; ALT: alanine aminotransferase; AST: aspartate aminotransferase; BLPP: biotin-/lactobionic acid–modified poly(ethylene glycol)-poly(lactic-co-glycolic acid)-poly(ethylene glycol); CK: creatine kinase; CKMB: creatine kinase MB; hCNT: human concentrative nucleoside transporter; H&E: hematoxylin and eosin; LDH: lactate dehydrogenase; NF-қB: nuclear factor-kappa beta; PCNA: proliferating cell nuclear antigen; SHH: sonic hedgehog; SMO: smoothened; VEGF: vascular endothelial growth factor; 5-FU: 5-fluorouracil.