Table 1.
Summary of FUS parameters utilized and therapeutic payload delivered in the studies covered in the Pre-Clinical Delivery of Therapeutic Agents section. It should be noted that the studies provide different levels of detail in their methodology, including FUS pulsing parameters and MB dosage, composition, and size distribution. Here, we have highlighted as many FUS parameters as could be determined from the studies. MBs can be formulated with a wide variety of shell materials, gas cores, charges, functional group attachments, size distributions, and concentrations. These features may differentially impact the bioeffects of the MBs upon FUS application. It is difficult to draw definitive conclusions on their relative contributions due to a lack of standardization within the field with regards to reporting and controlling for these characteristics.
| Disease | Ref. | Animal model | Delivered agent | FUS Parameters f = frequency; dc = duty cycle; BL = burst length; PRF = pulse repetition frequency; PNP = peak negative pressure; I = Intensity t = time |
MB type |
|---|---|---|---|---|---|
| Alzheimer’s Disease (AD) | [27] | APPswe/PSENl-dE9 transgenic mice | GSK-3 inhibitor | f = 0.4 MHz; BL = 10 ms; PRF = 1 Hz; PNP = 0.41 MPa; t = 60 s | SonoVue® SF6-filled |
| [28] | TgCRND8 transgenic mice | TrkA-agonist | f = 1.68 MHz; BL = 10 ms; PRF = 1 Hz; PNP = 1.29 MPa; t = 120 s | Definity | |
| [29] | TgCRND8 transgenic mice | TrkA-agonist | f = 1.68 MHz; BL = 10 ms; PRF = 1 Hz; PNP = 1.29 MPa; 120 s | Definity | |
| [30] | TgCRND8 Transgenic mice | Intravenous immunoglobulin (IVIg) | f = 1.68 MHz; BL = 10 ms; PRF = 1 Hz; t = 120 s | Definity | |
| [31] | APPswe/PSddE9 transgenic mice | anti-pGlu3 Aβ mAb | f = 0.835 MHz; BL = 10 ms; PRF = 2 Hz; PNP = 0.33 MPa; t = 100 s | Optison™ | |
| [32] | APP/PS1 transgenic mice | Quercetin-modified sulfur nanoparticles | PNP = 1 MPa; t = 600 s | Poly(α-cyanoacrylate nbutyl acrylate) | |
| [33] | TgCRND8 Transgenic mice | rAAV1/2 | f = 1.68 MHz; BL = 10 ms; PRF = 1 Hz; t = 120 s | Definity | |
| [34] | TgCRND8 transgenic mice | rAAV9 | f = 1.68–1.78 MHz; BL = 10 ms; PRF = 1 Hz; t = 120 s | Definity | |
| [35] | pR5 tau transgenic mice | Single chain antibody fragment RN2N | f = 1 MHz; dc = 10 %; BL = 10 ms; PRF = 10 Hz; PNP = 0.7 MPa; t = 6 s/spot | Phospholipid shell, octafluoropropane gas core | |
| [36] | pR5 tau transgenic mice | RN2N IgG | f = 1 MHz; dc = 10 %; BL = 10 ms; PRF = 10 Hz; PNP = 0.6 MPa; t = 60 s | Phospholipid shell, octafluoropropane gas core | |
| Parkinson’s Disease (PD) | [37] | Human α-syn expressing transgenic mice | rAAV9 | f = 1.68 MHz; BL = 10 ms; PRF = 1 Hz; PNP = 1.0–1.1 MPa; t = 120 s | Definity |
| [38] | C57BL/6 mice | α-syn plasmid | f = 0.4 MHz; BL = 10 ms; PRF = 1 Hz; PNP = 0.3 MPa; t = 60 s | SonoVue® SF6-filled | |
| [39] | MPTP mice | Curcumin | f = 1 MHz; BL = 200 ms; PRF = 1 Hz; PNP = 0.24–0.45 MPa; t = 60 s | Lipid-PLGA nanobubbles | |
| [40] | MPTP mice | GDNF plasmid liposome | f = 0.5 MHz; BL = 10 ms; PRF = 1 Hz; PNP = 0.3–0.8 MPa; t = 60 s | Avidinylated MBs conjugated with LpDNA | |
| [41] | 6-OHDA rats | GDNF plasmid | f = 1 MHz; cycle number = 5,000; PRF = 1 Hz; PNP = 0.7 MPa | GDNFp-loaded cationic microbubbles | |
| [42] | 6-OHDA rats | Nrf2 | f = 0.5 MHz; t = 30 s | Nrf2-loaded cationic nanomicrobubbles | |
| [43] | 6-OHDA rats | GDNF-loaded BPNs | f = 1.15 MHz; BL = 10 ms; PRF = 0.5 Hz; PNP = 0.6 MPa; t = 120 s | Albumin-shelled, octofluoropropane gas core | |
| [44] | 6-OHDA rats | GDNF-loaded PEGylated liposome | f = 1 MHz; dc = 20 %; I = 2 W/cm2 | Avidinylated biotinylated lipid-shelled | |
| [45] | MitoPark mice | polyethylenimine superparamagnetic iron oxide plasmid DNA | f = 1 MHz; cycle number = 5000; PRF = 1 Hz; PNP = 0.3 MPa; t = 60 s | Lipid-shelled | |
| [46] | MPTP mice | AAV-GDNF and neurturin (NTN) | f = 1.5 MHz; PRF = 10 Hz; PNP = 0.45 MPa; t = 60 s | In-house polydisperse | |
| [47] | MPTP mice | BDNF | f = 1.5 MHz; BL = 6.7 ms; PRF = 10 Hz; PNP = 0.45 MPa; t = 60 s | Size-isolated lipid-shelled | |
| [48] | C57BL/6 mice | BDNF | f = 1.5 MHz; BL = 6.7 ms; PRF = 5 Hz; PNP = 0.45 MPa; t = 60 s | Lipid-shelled, perfluorobutane core | |
| Glioblastoma Multiforme (GBM) | [51] | U87-luc and patient-derived 6240-luc Mice | Carboplatin | f = 1.05 MHz; BL = 23.8 ms; PRF = 1 Hz; PNP = 0.3 MPa; t = 120 s | SonoVue® |
| [52] | MGPP3 (Pdgf+/Pten−/−/P53−/−) Mice | Etoposide | f = 1.5 MHz; BL = 1 ms; PRF = 5 Hz; PNP = 0.7 MPa; t = 30 s | In-house polydisperse, lipid-shelled | |
| [54] | C6 Rats | Liposomal temozolomide nanoparticles | f = 1 MHz; cycle number = 10,000; PRF = 1 Hz; PNP = 0.8 MPa; t = 60 s | In-house lipid-shelled, perfluoropropane gas core | |
| [55] | Patient-derived glioma Mice | Paclitaxel | f = 1 MHz; BL = 12 ms; PRF = 1 Hz; PNP = 0.3 MPa; t = 120 s | Lumason | |
| [56] | U87 and B16F1ova Mice | ZsGreen BPNs and Luc-BPNs | f = 1.1 MHz; BL= 10 ms; PRF = 0.5 Hz; PNP = 0.55 MPa; t = 120 s | Albumin-shelled | |
| [57] | T98G Mice | pCas9/MGMT-loaded cRGD Lipid-polymer hybrid nanoparticles (LPHNs) | I = 1.84 W | In-house avidinylated biotinylated lipid-shelled conjugated to LPHNs-cRGD | |
| [58] | GL261 Mice | PEG-b-PMBSH nanoparticles | f = 1 MHz; dc = 0.5 %; cycle number = 5,000; PRF = 1 Hz; PNP = 0.3–0.7 MPa; t = 60 s | In-house cationic lipid-shelled | |
| [59] | 3-Gy irradiated Mice | Trypan blue dye solution | f 0.69 MHz; BL = 10 ms; PRF = 2 Hz; PNP = 0.26–0.27 MPa; t = 95 s | Optison | |
| [60] | GL261 Mice | mCD47 | f = 1.1 MHz; dc = 0.5 %; PNP = 0.4 MPa; t = 120 s | Albumin-shelled | |
| [61] | Patient-derived glioma Mice | 89Zr-radiolabelled antibody targeting EphA2 receptors | f = 1.1 MHz; BL = 10 ms; PRF = 0.4 Hz; PNP = 0.85 MPa; t = 120 s | Definity | |
| [62] | eGFP-transduced U87 and GL261 Mice | eGFP mRNA | f = 1.44 MHz; dc =1%; BL = 10 ms; PRF = 1 Hz; PNP = 3.82 MPa; t = 120 s | In-house lipid-shelled, perfluorobutane core | |
| [63] | eGFP-transduced U87 and GL261 Mice | eGFP mRNA | f = 1.44 MHz; dc = 1 %; BL = 10 ms; PRF = 1 Hz; PNP = 3.82 MPa (U87) and 1.52, 2.74, 3.53 MPa (GL261); t = 120 s | In-house lipid-shelled, perfluorobutane core | |
| [64] | Porcine model Normal brain tissue | GFAP and myelin basic protein release | f = 0.65 MHz; BL = 10 ms; PRF = 1 Hz; PNP = 1.5 MPa; t = 180 s | Definity | |
| Temporal Lobe Epilepsy | [65] | Rat model pilocarpine | N/A | f = 0.65 MHz; dc = 2 %; BL = 20 ms; PRF = 1 Hz; PNP = 0.4 MPa; t = 90 s | Definity |
| [66] | CD-1 mice | Quinolinic acid | f = 1.5 MHz; dc = 2 %; BL = 20 ms; PRF = 1 Hz; PNP = 0.33, 0.5, 0.67 MPa; t = 120 s | Definity | |
| [67] | Sprague Dawley rats | Quinolinic acid | f = 1.5 MHz; dc = 2 %; BL = 20 ms; PRF = 1 HZ; PNP = 0.69 MPa; t = 120 s | In-house PEG lipid-shelled, decafluorobutane gas core | |
| Stem Cell Delivery for CNS Disorders | [70] | Sprague Dawley rats | Iron labeled GFP neural stem cells | f = 0.558 MHz; BL = 10 ms; PRF = 1 Hz; PNP = 0.24 MPa; t = 120 s | Definity |
| [72] | Sprague-Dawley rats | SPION-loaded hNPCs | f = 1.5 MHz; BL = 10 ms; PRF = 10 Hz; PNP = 0.45 MPa; t = 60 s | monodisperse microbubbles (SIMB4-5) | |
| [73] | Sprague–Dawley rats | Mesenchymal stem cells | f = 0.515 MHz; BL = 10 ms; PRF = 1 Hz; PNP = 0.25 MPa; t = 300 s | Definity |