br ensures moderate monodispersity in
ensures moderate monodispersity in aqueous solution (Fig. 1b) . Fig. 3b. Compared to the tumors treated with laser alone that received
The Zeta potential of ACA nanocomplex was -35.1 mV that proves the no significant thermal dose (8.67 × 10−2), the tumors loaded with the
good stability of the nanocomplex (Fig. 1c). The UV–vis spectrum in- nanocomplex received much greater thermal doses. Moreover, as ex-
dicates that ACA nanocomplex has an Spectinomycin peak at 530 nm which pected from thermometry results, the tumors treated with the nano-
matches with the laser wavelength used in this study (Fig. 1d).
complex received the varied amounts of thermal dose at the three dif-
ferent sessions in spite of the same treatment conditions used during the
3.2. Biodistribution of ACA nanocomplex
experiments. After 15 min laser irradiation, the tumors treated with
The tumor accumulation of the nanocomplex was investigated at 6, whereas this value was remarkably enhanced to 8.37 × 10+2 min (S2)
Fig. 1. Characterization of ACA nanocomplex. (a) TEM image of ACA nanocomplex, showing that AuNPs are coated by alginate (arrow indicates alginate coating).
(b) Hydrodynamic size distribution of ACA nanocom-plex by DLS with highest frequency around 44 nm. (c) Zeta potential of ACA nanocomplex with the peak in-tensity of -35.1 mV. (d) UV–vis spectrum of ACA na-nocomplex with the peak absorption at 530 nm.
M. Mirrahimi, et al.
Fig. 2. (a) Time-dependent tumor accumulation of ACA nanocomplex at 6, 12 and 24 h after the intraperitoneal injection. (b) ICP-MS analysis of the Au content of various organs 24 h after the intraperitoneal administration of ACA nanocomplex.
Fig. 3. (a) Temperature rise profile of the tumor under 15 min laser irradiation. (b) The values of thermal dose received by the tumors treated with laser alone (the average of the three sessions) and ACA + laser (at diﬀerent sessions). (c) The representative infrared thermal image of the tumor bearing mice upon laser irradiation at diﬀerent sessions.
3.4. In vivo antitumor assessment
Fig. 4 represents the schematic of in vivo study protocol for the antitumor assessment of various treatments. To evaluate the in vivo tumor inhibition eﬃcacy of the treatments, the variations in the tumor size of the mice were recorded during 21 days after treatment start (Fig. 5a, b). The mice which were injected with nothing were con-sidered as blank control. The laser irradiation alone and chemotherapy with free cisplatin delayed the tumor growth to some extent, showing a tumor growth inhibition rate of 34% and 45%, respectively. In contrast, photothermal therapy alone (AuNP + Laser) and chemotherapy with ACA nanocomplex at the same cisplatin concentration caused a notably greater inhibition rate of 73% and 81%, respectively. The re-presentative photographs of the mice during study period (Fig. 5a), the
photographs and the weight of the typical tumors extracted on the day 21 (Fig. 5c, d) obviously indicate that the combined chemo-photo-thermal therapy results in the best antitumor activity. The in-traperitoneal injection of ACA nanocomplex followed by laser irradia-tion (24 h post-injection) for three sessions dramatically suppressed tumor growth (> 95%) and left a black scar at the tumor site, showing the evidence of extensive tumor necrosis. All mice in ACA + laser group remained alive, and 60% of them revealed no evidence of recurrence until the end of the 45 days follow-up period, whereas the other groups had growing tumors and showed significantly lower survival rates (Fig. 6).