Table 3:
Photothermal therapy (PTT): preclinical studies.
| Author | Year | Animal model | Nanoparticles | Type of study | Results |
|---|---|---|---|---|---|
| Takagi | 2008 | Mice (n=76) | MWCNT | Phase I | The highest mortality, MWCNT group followed by the Crocidolite group → study was terminated at week 25 (180 days)MWCNT induced mesothelioma along with Crocidolite (positive control) |
| Muller | 2009 | Rat | MWCNT | Phase I | After 24 months, MWCNT with or without structural defects did not induce mesothelioma (4 or 6 %, respectively). while Crocidolite induced a clear carcinogenic response (34.6 % animals with mesothelioma vs 3.8 % in vehicle controls). |
| The incidence of tumors other than mesothelioma was not significantly increased across the groups | |||||
| Zhang | 2010 | Mice | Gold nanoparticles |
Phase I | Gold nanoparticles at low concentrations do not cause appreciable toxicity |
| Obvious effects on organ index have been observed at high concentration. | |||||
| Toxicity: More important for orally administration (significant decreases in body weight, spleen index, and red blood cells) and intraperitoneal routes than IV injection | |||||
| Bagley | 2013 | Mice | PEG-NRs | Phase II | Toxicity and effectiveness of implanted NIR illumination source: |
| – Initial temperature change after 50 s of direct implanted NIR illumination in (e) tumors, (f) intestine, and (g) liver → More important in PEG-NR treated animals versus controls | |||||
| – Maximal temperature change for tumor, liver, and intestine of PEG-NR treated animals (n=5 per tissue) → significant accumulation of PEG-NRs in the liver | |||||
| – Histology and Ki-67 immunohistochemical staining of tissues following PEG-NR therapy with implanted NIR device. | |||||
| No tissue damage or proliferative defects in intestine/Thermal effects were more modest than in ovarian tumors or the liver | |||||
| – Quantification of doxorubicin-loaded liposomes and AngioSPARK750 in tumor 3 h after injection and PEG-NR/Implant NIR therapy or injection only → concentration was superior for PEG-NRs+implant NIR | |||||
| Rittinghausen | 2014 | Rats (n=500) | MWCNT | Phase I | Mortality: At the end of the experimental time after 24 months mortality was: |
| 80 % in the MWCNT A and B low- and high-dose groups and in the MWCNT C high-dose group | |||||
| 56 % in the MWCNT D low-dose group | |||||
| 76 % in the amosite asbestos group (positive control) | |||||
| and 34 % in the negative control group | |||||
| Histopathological findings: | |||||
| → Malignant mesotheliomas of the peritoneum | |||||
| MWCNT A groups: 98 % (high-dose) and 90 % (low-dose) | |||||
| MWCNT B groups: 90 % (high dose) and 92 % (low dose) | |||||
| MWCNT C groups: 94 % (high dose) and 84 % (low dose) | |||||
| MWCNT D groups: 70 % (high dose) and 40 % (low dose) | |||||
| Amosite asbestos group: 66 % | |||||
| Medium control group: 1 mesothelioma (2 %) | |||||
| → granulomas on the peritoneal surface: most of the MWCNT-treated rats | |||||
| Diddens-Tschoeke | 2015 | Mice (n=34) |
PdNc(OBu)8 | Phase II | Histology/Necrosis: In contrast to the control groups, the central area of the tumor tissue treated during 15 and 20 s was completely necrotic. Adjacent peripheral normal tissue including skin and muscle remained completely unaffected. |
| Nowacki | 2015 | Mice (n=60) | A0-o-CX-chem-CD133 | Phase III | 12 groups: 4 controls, 8 study groups (labeled as: C1, C2, C3, A0-o-C1-chem, A0-o-C2-chem, A0-o-C3-chem, A0-o-C1-chem-CD133, A0-o-C3-chem-CD133) |
| Toxicity: necrosis → differences in the evolution of the metastatic and infiltration processes in each of the experimental groups. | |||||
| Survival: | |||||
| The first animal death: 4th day, in group C1 | |||||
| The longest individual survival rate: 16th day, group A0-o-C1-chem-CD133 | |||||
| The shortest general survival (8 days): control group K3 | |||||
| The longest survival (12.6 days): group A0-o-C1-chem-CD133 (p=0.05) | |||||
| The survival rates for the other control groups were as follows: K1 – 11.0 days; K2 – 9.0 days and K4 – 8.4 days. | |||||
| Wu | 2015 | Mice | pSGNs | Phase II | Necrosis: Mice with ovarian PC, treated with pSGNs (OD800=1.5) or 10 % trehalose and irradiated with an 808-nm NIR laser → IP lavage → annexin V and propidium iodide |
| The percentage of necrosis in cancer cells was significantly increased in the groups that received IP PTT mediated by pSGNs | |||||
| Toxicity: damage of normal tissues in the intraperitoneal cavity → TUNEL assay | |||||
| No noticeable damage in normal tissues (liver, kidney, spleen, intestinal epithelium) | |||||
| Chemoluminescent intensity: The NIR laser irradiation was repeated every 3–4 days. IP administered pSGNs combined with NIR laser irradiation significantly inhibited tumor growth compared with the control, NIR-only, and pSGNs-only groups in both tumor cell | |||||
| models. Repeated PTT can inhibit IP tumor growth in vivo. | |||||
| Conjugating pSGNs with anti-human CD47 monoclonal antibody: | |||||
| The group treated with anti-human CD47 conjugated pSGNs and NIR laser irradiation had the strongest therapeutic effect on the human ovarian cancer cell xenograft model. | |||||
| Zhang | 2018 | Mice | C-GERTs | Phase III | Toxicity: Histological analysis of major organs (liver, lung, kidney, heart, and spleen) → no obvious signs of toxicity are found in the harvested organs |
| Bioluminescence: The C-GERTs+laser group shows the best therapeutic effect, with near complete elimination of tumors and suppression of regrowth | |||||
| Total flux (TF) value 20th days: | |||||
| – saline and cisplatin: increased to more than 600 % of the initial value | |||||
| – C-GERTs+laser group: near complete elimination of tumors and suppression of regrowth; average TF value decreased to about 37 % 20 days after treatment. | |||||
| The extent of tumor dissemination in the abdominal cavities: significant reduction in tumor number, size, and weight in the GERTs+laser group | |||||
| GERTs+laser group: few small intra-abdominal tumors (5 per mouse). | |||||
| C-GERTs+laser group: 80 % of mice were completely cured, with just 2 mice found to have 1 small tumor remaining each. | |||||
| The average tumor weight in the C-GERTs+laser group was significantly reduced to 0.03±0.05 g per mouse → tumor weights in the saline+laser, cisplatin, C-GERTs, and GERTs+laser groups (≈0.80±0.14, 0.55±0.08, 0.41±0.06, and 0.18±0.15 g per mouse, respectively) | |||||
| Survival: The C-GERTs+laser group achieves a survival rate of 100 % during the observation period (35 days). All mice in the other four groups eventually succumbed to their tumors, with survival times of 26.33±2.05, 24±1.63, 25.33±2.05, and 31.67±1.25 days for saline+laser, cisplatin, C-GERTs, and GERTs+laser groups, respectively |
PdNc(OBu)8, Palladium 5,9,14,18,23,27,32,36-octabutoxynaphthalocyanine; MWCNT, multi-wall carbon nanotubes; A0-o-CX-chem-CD133, nanovehicles based on anti-CD133 antibodies bioconiugated to carbon nanotubes loaded with platinum (Pt) -prodrugs; PEG-NRs, polyethylene glycolcoated gold nanorods; pSGNs, pegylated silica-core gold nanoshells; C-GERTs, cisplatin-loaded gap-enhanced Raman tags; IV, intravenous; IP, intra peritoneal