Comparing the Effects of Light- or Sonic-Activated Drug Delivery: Photochemical/Sonochemical Internalization

Abstract

Photochemical internalization (PCI) is a technique that uses the photochemical properties of photodynamic therapy (PDT) for the enhanced delivery of endolysosomal-trapped macromolecules into the cell cytoplasm. The released agent can therefore exert its full biological activity, in contrast to being degraded by lysosomal hydrolases. Activation of photosensitizers via ultrasound (US), called sonodynamic therapy (SDT), has been proposed as an alternative to light-activated PDT for the treatment of cancerous tumors. The use of focused US (FUS) to activate photosensitizers allows treatment at tumor sites buried deep within tissues, overcoming one of the main limitations of PDT/PCI. We have examined ultrasonic activation of photosensitizers together with the anticancer agent bleomycin (BLM) using sonochemical internalization (SCI), as an alternative to light-activated PCI. Our results indicate that, compared to drug or US treatment alone, US activation of the photosensitizer AlPcS2a together with BLM significantly inhibits the ability of treated glioma cells to form clonogenic colonies.

Synergistic Efficacy of Ultrasound, Sonosensitizers and Chemotherapy: A Review

“…The results shown in Figure 5B, employing this model, demonstrated that SDT potentiated the cytotoxic effects of BLM to a significant degree. This was the case regardless of the sequence of SDT and BLM application, although SDT before drug was more effective [42,45]. This synergistic effect is postulated to be due to endosomal escape, in a similar manner to that seen for light-based PCI [46,47].…”

“…The overall damage induced by SDT is closely related to the precise subcellular localization of the sonosensitizer. Figure 3 [42]. Fluorescence microscopy was used to verify the uptake and intracellular localization of AlPcS 2a in the absence or presence of FUS.…”

“…Spheroids are 3D aggregates of cells that mimic microtumors and metastases. In comparison to monolayer cultures, a significant advantage of this model is that their microenvironment more closely mimics the in vivo situation Reproduced with permission from [42].…”

Nanosensitizers for sonodynamic therapy for glioblastoma multiforme: current progress and future perspectives

“…Several studies have explored the molecular mechanisms of SDT for GBM treatment through in vitro and in vivo experiments. Many drugs, including 5-ALA [ 44 – 52 ], fluorescein [ 53 ], rose Bengal [ 54 ], hematoporphyrin mono-methyl ether (HMME) [ 38 , 55 – 60 ], sino-porphyrin [ 61 – 63 ], photofrin [ 64 , 65 ], photolon [ 66 , 67 ], protoporphyrin IX (ppIX) [ 52 ], talaporfin sodium [ 52 ], aluminum phthalocyanine disulfonate (AlPcS 2a ) [ 68 , 69 ], and titanium dioxide (TiO 2 ), have been used as sonosensitizers [ 70 , 71 ], which mainly accumulate in the mitochondria (Table 1 ).…”

“…SDT with US (1.0 MHz, duty cycle of 80%, 1.8 W/cm 2 , 1 min) exerted the greatest inhibitory effects on the viability of U87MGde 2–7 cells, with the highest generation of ROS. To compare the efficacy of SDT and PDT in combination with chemotherapy, Madsen et al [ 68 ] investigated ultrasonic and photic activation of AlPcS 2a together with the anticancer agent bleomycin (BLM) to treat F98 cells. The author aimed to compare the effects of photochemical internalization (PCI) and sonochemical internalization (SCI) on tumor cells.…”