Table 3.

Preclinical research on MRgFUS-facilitated targeted drug delivery

Disease indication	Drug category	Therapeutic agent of interest	Subject/disease model	FUS parameters*	Results	Year
Brain tumor	Conventional chemotherapy	Lipo-Dox	Rat/gliosarcoma	1700; 1.2; 10; 1; 60–120, 5–9 sonications in total	↓ tumor growth	20121 [16]
					↑ survival
		IL-4 targeted Lipo-Dox	Mouse/GBM	1000; 0.7; _; 1: _, 5% duty cycle	↓ tumor growth	20121 [24]
					↑ survival
		Lipo-Dox	Rat/gliosarcoma	690; 0.55–0.81; 10; 1; 60, 5–20 sonications in total, 3 weekly treatments	↓tumor growth,	2013 [8]
					↑ survival
		Free Dox	Mouse/GBM	612.5; 0.4; 10; 1; 180	↓ tumor growth	2014 [66]
					↑ survival
		BCNU	Rat/GBM	400; 0.62; 10; 1; 30	↓ tumor growth	2010 [73]
					↑ survival
		TMZ	Rat/gliosarcoma	500; 0.6; 10; 1; 60	↓ tumor growth	2013 [122]
					↑ survival
	Monoclonal antibody	Anti-HER2 Ab (Herceptin)	Mouse/normal	690; 0.6 or 0.8;10; 1; 40	Targeted Ab delivery	2006 [64]
		Anti-HER2 Ab (Herceptin)	Rat/metastatic breast cancer (HER2+)	690; 0.69; 10; 1; 60,6 weekly treatments	↓ tumor size	2012 [95]
					↑ survival
	Nanoparticle	Epirubicin immobilized on MNP	Rat/GBM	400; 0.62; 1; 10; 1; 120	↓ tumor growth	2010 [74]
					↑ survival
		BCNU immobilized on MNP	Rat/GBM	400; 0.7; 10; 1; 30	↓ tumor growth	2010 [23]
		Cisplatin immobilized on NP	Rat/gliosarcoma, GBM	1140; 0.6 or 0.8; _; _; 120,0.5% duty cycle	↓ tumor growth	2017 [114]
					↑ survival
	Gene therapy	HSV1-tk-loaded VCMBs/ganciclovir	Rat/GBM	1000; 0.7; _; 5; 120	↓ tumor growth	2013 [2]
					↑ survival
	Cells	NK-92 cells (chimeric HER2 antigen receptor+)	Rat/metastatic breast cancer (HER2+)	551.5; 0.33; 10; 1; 120	↑ NK-92 cell accumulation at the tumor sites	2013 [2]
		NK-92 cells (chimeric HER2 antigen receptor+)	Rat/metastatic breast cancer (HER2+)	551.5; _; 10; 2; 120	↓ tumor growth and	2016 [3]
					↑ survival in the front-loaded treatment
AD	Antibody	Anti-Ap Ab	Tg mouse/AD	690; 0.67–0.8; 10; 1; 40–45	↑ Ab delivery	2008 [98]
					↑ endogenous IgG
		Anti-Ap Ab (BAM-10)	Tg mouse/AD	558; 0.3; 10; 1; 120	↓ Aβ plaques	2010 [56]
	Nanoparticle	Anti-AS Ab (6E10) immobilized on NP	Tg mouse/AD	2500; 0.95–2.21; _; _; 60	↑ Ab delivery	2014 [125]
Parkinson's disease	Antibody	Anti-DRD4 Ab	Mouse/normal	690; 0.6-1.1; 10; 1; 40	↑ Ab delivery	2006 [65]
	Drug	Lipo-rhFGF20	Rat/6-OHDA lesioned	690; _; 10; 1; 60, 3 W	↑ drug delivery	2018 [90]
					↓ motor dysfunction
					↓ DA neuronal loss
Huntington’s disease	Gene therapy	cc-siRNA-Htt	Rat/normal	558; 0.3; 10; 1; 120	↓ Htt expression	2012 [13]
Unspecified	Gene therapy	AAV9-GFP	Mouse/normal	1180; 0.53-0.6; 10; 1; 120	Targeted GFP expression	2012 [113]
		AAV2-GFP	Mouse/normal	1500; 0.44-0.7; 10; 1; 120	Targeted GFP expression	2013 [46]

^*Frequency (kHz); negative peak pressure (MPa); burst length (ms); repetition frequency (Hz); total US duration (sec).

MRgHIFU : magnetic resonanceguided focused ultrasound, FUS : focused ultrasound, Lipo-Dox : liposomal doxorubicin, ↓ : inhibition/reduction, ↑ : increase, GBM : glioblastoma multiforme, _ : unspecified, BCNU : 1,3-Bis(2-chloroethyl)-1-nitrosourea, TMZ : temozolomide, HER2 : human epidermal growth factor receptor 2, Ab : antibody, MNP : magnetic nanoparticle, NP : nanoparticle, HSV1-tk : herpes simplex virus type 1-thymidine kinase, VCMB : VEGFR2-targeted and cationic microbubble, NK : natural killer, Aβ : amyloid-beta, AD : Alzheimer’s disease, IgG : immunoglobulin G, DRD4 : dopamine receptor D4, rhFGF20 : recombinant human fibroblast growth factor-20, OHDA : hydroxydopamine, Tg : transgenic, DA : dopaminergic, cc-siRNA : cholesterol-conjugated small interfering RNA, Htt : Huntingtin protein, AAV : adeno-associated virus, GFP : green fluorescent protein