br In addition the systemic
In addition, the systemic toxicity of the various treatments was as-sessed by recording the body weight of each group during the treatment course (Fig. 7). The body weight was increased in all groups as a result
Fig. 4. Schematic representation of the treatment protocol. (IP: intraperitoneal).
Fig. 5. Assessment of in vivo antitumor eﬃcacy against Balb/c mice bearing CT26 tumor model. (a) Representative photographs of the mice at Days 1, 7, 14 and 21 of the treatment course. (b) Tumor growth curve following diﬀerent treatments during 21 days of study (The error bars represent the standard deviation). (c) Representative photo and (d) the weight of CT26 tumors isolated from mice on day 21 (* P value < 0.05, ** P value < 0.01).
Fig. 6. Survival rate of CT26 tumor-bearing mice after various treatments at 45 days follow-up period.
Fig. 7. The body weight change of CT26 tumor-bearing mice during the treatment course.
of the growing tumor burden except the ACA + laser group that showed a slight decrease in body weight during the first week of the treatment course. However, the body weight of the mice treated with ACA + laser was increased by prolonging time and returned to its normal level, indicating the little adverse side eﬀect of this treatment.
3.5. Tumor metabolic activity
High [18F]FDG uptake in the tumor is correlated with high meta-bolic activity in viable tumor cells. Fig. 8 shows the coronal view of [18F]FDG-PET images of the mice receiving various treatments. As shown in this figure, the mice treated with ACA + laser indicated no evidence of [18F]FDG uptake and then metabolic activity at the tumor
site. This represents that beside the macroscopic level, the combination of ACA nanocomplex and laser irradiation can eradicate tumor Thapsigargin even at microscopic level. Table 1 compares the tumor metabolic parameters derived from PET images of the mice receiving various treatments where ACA + laser resulted in the lowest tumor metabo-lism. Meanwhile, the mice treated with cisplatin and ACA alone ex-hibited a significantly decreased tumor metabolism compared to the control.
Recent years have seen remarkable evolution in the design and application of numerous nanomaterials in cancer nanotechnology.
M. Mirrahimi, et al.
Fig. 8. Coronal view of [18F]FDG-PET image of Balb/c mice bearing CT26 tumor receiving various treatments on the10th day of study period (arrows indicate tumor site). The ACA + laser group has no evidence of [18F]FDG up-take at the tumor site that implies the absence of viable tumor cells.
Tumor metabolic parameters extracted from [18F]FDG-PET images of Balb/c mice bearing CT26 tumor receiving various treatments.
Metabolic parameters Control Cisplatin ACA ACA + LASER
AuNPs with a number of physical properties have been the subject of intensive research in biomedical applications especially cancer diag-nosis and therapy [19–21]. In recent years, we have conducted nu-merous researches in the area of cancer nanotechnology with the spe-cial focus on AuNPs [22–29]. In this regard, the photoresponsive features of AuNPs in combination with laser exhibited promising results for photothermal ablation of cancer cells [30–33]. Altogether, the summary of our recent eﬀorts revealed that AuNPs based photothermal therapy was not so eﬃcient to eradicate all the tumor cells. As a result, the remaining living cancer cells may contribute to tumor relapse or metastasis. Therefore, photothermal therapy needs to be coupled with other modalities such as chemotherapy to achieve a stronger anticancer eﬃcacy.
Multi drug resistance (MDR) is a major impediment toward the successful treatment following cancer chemotherapy. The major me-chanism of MDR has been found to be attributed with the over-expression of ATP-binding cassette (ABC) transporters, mostly Pglycoprotein (P-gp). This causes increased eﬄux pumping of drugs out of the plasma membrane and subsequently lowering the intracellular drug supply [34,35]. A report by Wang et al. revealed that the MDR issue can be potentially overcome by the use of a drug delivery system based on AuNPs . They demonstrated that gold-doxorubicin (Au-DOX) nanoconjugates significantly increased the intracellular drug ac-cumulation in MDR cancer cells compared to free DOX, thereby indu-cing greater cell cytotoxicity. Apart from enhancing the intracellular drug dosage, nucleus targeting is another eﬀective strategy to address the MDR issue by completely bypassing the P-gp. Several reports proved that AuNPs can be able to penetrate the cell nucleus, especially when functionalized with proper ligands, and subsequently deliver the drug payloads to the nucleus [37,38].