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. 2023 Jun 8;11:1212193. doi: 10.3389/fchem.2023.1212193

TABLE 1.

Mitochondria-targeted organic SDT agents for cancer therapy.

SDT agent Probe construction US irradiation Cell viability (off-target vs. mitochondria-targeted SDT) Therapeutic strategy Reference
IR780 PFP/IR780 core-shell nanodroplets (IR780-NDs) 3 min <40% for IR780-NDs vs. >90% for NDs (w/o IR780) cell viability of 4T1 cells at 121 μg/mL Combination of mitochondria-targeted SDT, deep penetration, and FL/PA imaging visualization Zhang et al. (2019)
650 kHz
2.4 W/cm2
IR780 R162/IR780 TPP-based lipid bilayer (MLipRIR NPs) 1 min 16.4% for MLipRIR NPs vs. 27.6% for LipRIR NPs (w/o TPP) cell viability of 4T1 cells at 1 μg/mL (R162 conc.) Combination of mitochondrial SDT and immunotherapy (w/R162) Ren et al. (2021)
1.0 MHz
1.5 W/cm2
50% duty cycle
IR780 HSA-NO/FDC nano-formulation (PIH-NO) 1 min 30% for PIH-NO vs. 50% for PIH (w/o HSA-NO) and 70% for IH (w/o HSA-NO and FDC) cell viability of 4T1 cells at 4 μg/mL (IR780 conc.) Combination of mitochondria-targeted SDT and gas therapy (w/HSA-NO and FDC) Ji et al. (2021)
1.0 MHz
1.5 W/cm2 50% duty cycle
IR780 IR780/CPI-613/adipocyte-derived organelle LDs (CPI-613/IR780@LDs) 1 min <40% for CPI-613/IR780@LDs cell viability of both normoxic and hypoxic Panc02 cells at 20 μmol/L Combination of mitochondria-targeted SDT and metabolic modulation therapy (w/CPI-613) Shi et al. (2023)
1 MHz
0.5 W/cm2
50% duty cycle
ALA ALA/2-DG/MB 5 min 33.2% for ALA/2-DG/MB vs. 49.2% for ALA/2-DG cell viability of HepG2 cells at 2 mmol/L (2-DG) Combination of mitochondria-targeted SDT, metabolic modulation therapy (w/2-DG), and US-stimulated microbubble therapy (w/MB) Xie et al. (2017)
3 MHz
2 W/cm2
60% duty cycle
HMME HMME/TPP-Chol liposome (HMME-Lipo-TPP) 3 min ∼32% for HMME-Lipo-TPP vs. ∼44% for HMME-Lipo (w/o TPP) cell viability of MCF-7 cells at 20 μg/mL US-assisted increased cancer cells mitochondria delivery Chen et al. (2017b)
1 MHz
0.5 W/cm2
Ce6 TPP-Ce6/PL/EV (EV (TPP-Ce6/PL) 1 min ∼6.5% for EV (TPP-Ce6/PL) vs. ∼30% for EV (TPP-Ce6) and ∼70% for TPP-Ce6 cell viability of MCF-7 cells at 10 μM (TPP-Ce6 (or Ce6) conc.) Combination of mitochondria-targeted SDT and chemotherapy (w/PL) Cao et al. (2023)
1 MHz
0.3 W/cm2
IR780/HMME IR780/HMME/GOx/PLGA core-shell nano-formulation (IHG@P) 30 s 8.48% for IHG@P vs. ∼68% for starvation therapy alone and ∼58% for SDT therapy alone cell viability of 4T1 cells at 60 μg/mL (PLGA conc.) Combination of mitochondria-targeted dual SDT agent therapy, starvation therapy (w/GOx), and FL/PA imaging visualization Zhang et al. (2020)
2 W/cm2
IR780/Ce6 PEG-IR780/Ce6 nano-micelle (PEG-IR780@Ce6) 3 min 35% for PEG-IR780@Ce6 vs. 85% for free Ce6 and 43% for PEG-IR780 cell viability of MDA-MB-231 cells at 40 μg/mL Mitochondria-targeted dual SDT agent therapy Han et al. (2021)
1 MHz
0.6 W/cm2
50% duty rate)
Gd(III)- porphyrinate TPP-Gd(III) porphyrinate/MAL-PEG-b-PDPA pH-responsive nanomicelle (RPGdP) 1 min 25% for RPGdP vs. 65% for RPGd (w/o TPP) cell viability of H22 cancer cells at 80 μg/mL Combination of mitochondria-targeted SDIT and MR imaging visualization Li et al. (2022)
1 MHz
1.5 W/cm2

[Abbreviation] PFP: perfluoropentane, NDs: nanodroplets, w/o: without, PA: photoacoustic, FL: fluorescence, MR: magnetic resonance, R162: glutamate dehydrogenase 1 inhibitor, TPP: triphenylphosphonium, conc.: concentration, HSA-NO: human serum albumin-based NO donor, FDC: perfluorodecalin, CPI-613: FDA-approved TCA cycle inhibitor, LDs: lipid droplets, w/: with, ALA: 5-aminolevulinic acid, 2-DG: glycolysis inhibitor 2-deoxyglucose, MB: microbubble, HMME: hematoporphyrin monomethyl ether, Chol: cholesterol, Ce6: Chlorin e6, PL: prooxidant piperlongumine, EV: extracellular vesicle, GOx: glucose oxidase, PLGA: polylactic-co-glycolic acid, SDIT: sonodynamic immunotherapy SDT: sonodynamic therapy.