5-Aminolevulinic acid hydrochloride loaded microbubbles-mediated sonodynamic therapy in pancreatic cancer cells

Abstract

5-Aminolevulinic acid hydrochloride (ALA)-mediated sonodynamic therapy (SDT) had anti-tumour effect on pancreatic cancer cells. Hence, ALA loaded lipid/poly(lactic-co-glycolic acid) (PLGA) microbubbles (MBs)-mediated SDT for pancreatic cancer has great potential. The average size of ALA-lipid MBs and ALA-PLGA MBs was about 3.0 mm. The two kinds of MBs had good biocompatibility to normal HPDE6-C7 cells and were not toxic to pancreatic cancer cells. Compared with ALA-induced SDT, a statistically significant decrease in cell viability was observed in ALA lipid/PLGA MBs combined with ultrasound groups in AsPC-1 and BxPC-3 cells (p < .05). Obvious effect on the apoptotic rate, apoptosis and pyroptosis morphology, enhanced reactive oxygen species was found in ALA-lipid/PLGA MBs mediated SDT in vitro. Through in vivo study, we found ALA-lipid/PLGA MBs-mediated SDT was a promise treatment for pancreatic cancer.

Nanotechnology-enabled sonodynamic therapy against malignant tumors

“… 124 Additionally, hyperthermic cells can also be killed by a non-thermal effect (cavitation and direct effect) of US under various gas conditions. 125 Yang et al 126 reported that compared with SDT alone, SDT combined with 5-ALA mediated hyperthermia could inhibit the growth of human glioma more effectively by in vitro and in vivo experiments. As a new kind of light and sound responsive nanomaterial, ALA-lipid/PLGA MB-mediated SDT was a promising treatment for pancreatic cancer.…”

Latest Advances in the Use of Therapeutic Focused Ultrasound in the Treatment of Pancreatic Cancer

“…It should be noted that in the absence of hyperthermia treatment of the tumours, their non-liposomal doxorubicin concentration was approximately eight times higher than that when liposomal doxorubicin was used (parameters: f = 1.2 MHz, Power = 7 W, d.c = 100%, T = 41.2 ± 1.3 • C) [174]. Additional studies have shown that the delivery of gemcitabine to pancreatic tumours was enhanced by sonoporation in human pancreatic MiaPaCa-2 tumours grown orthotopically in mice [175], while the combination of sonodynamic therapy with various anti-cancer compounds, including 5-aminolevulinic acid [176,177], 5FU [178,179], antibiotic and root extracts [180], gemcitabine [181], nanocomposites able to generate reactive oxygen species or nitric oxide [182][183][184], radiation [185] and epirubicin [186], have provided proof of concept for the intriguing potential that sonodynamic therapy has in pancreatic cancer.…”

The Role of Nonapoptotic Programmed Cell Death — Ferroptosis, Necroptosis, and Pyroptosis — in Pancreatic Ductal Adenocarcinoma Treatment

“…5-Aminolevulinic acid hydrochloride (ALA) is an effective sonosensitizer. Yang and colleagues indicated that ALA-loaded lipid/poly(lactic-co-glycolic acid) (PLGA) microbubble (MB)-mediated SDT induces the pyroptosis of AsPC-1 and BxPC-3 cells because the combination of MBs and ultrasound can facilitate cell membrane permeability and cause cell swelling ( 88 ).…”