Table 1.

The values of various parameters, i.e. NM composition, NM average sizes, ultrasound frequency/intensity/focusing/MI, and their associated in vitro and in vivo anti-tumor efficacies as well as mechanisms of action, where tumor diagnosis and therapy are covered

NM composition	NM average size	Therapy (Th) Diagnosis (Di)	Ultrasound parameters Intensity (I); Frequency (f); Mechanical index (MI); focused (fo) vs unfocused (ufo)	In vitro/In vivo/ex vivo efficacy	Mechanism of action	References
MNP + DOX at the surface of MB	MB: 0.4–200 µM MNP (Fe3O4): 50 nm	Th	f = 0.5–2 MHz Oscillation thresold: 0.4 bar Pressure either above or below 0.5 bar Focused transducer	Delivery of MNP + DOX to mouse tumor tissue	Release of MNP/DOX from MB by ultrasounds above oscillation threshold Diffusion of MNP from MB by several 100 µm	[47]
Magnetic Polylactic co-glycolic acid Nanocapsules (MNC) + 5-fluorouracil	70 nm	Di: PA	f = 3 MHz I between 0,3 and 1 W/cm2	NA	Release of + 5-fluorouracil from MNC (increasing release with increasing US intensity)	[205]
Phosphilpid NB Phosphilipd MB Self-assembled amphiphilic polymers (hydrophobic core + hydrophilic exterior): MI	MB: 1–4 µm (Definity, CAV) NB: 100–500 nm MI: 10–100 nm	Di	Frequency larger than 20 MHz	NA (review)	1/ NB: diffuse in tumor by EPR, requires pluoronic acid to be echogenic, can transport drugs; 2/ MB: does not diffuse to tumor via EPR, highly echogenic; 3/ MI: diffuse to tumor via EPR; requires specifc phospholipid concentration to be echogenic, unstable	[33]
Nanodroplet (ND) loaded with Iodine	60 nm	Di	B-mode imaging	iv injection of ND in mice bearing Hepatocellular carcinoma	ND targets liver and hepatocyte Precise tumor volume measurement CT + US CA combined	[27]
Silica NC containing NIR-dyes-modified polymers and ultrasmall gold NP	Silica NC: 100 nm	Di	f = 13–24 MHz	Combination of US and PA features of Silica NC validated ex vivo	Silica NC: US CA Gold NP: PA CA	[41]
MB liposomes conjugated with anti-Her2 antibodies loaded with survivin-targeted siRNA and doxorubicin	NA	Th	f = 5–12 MHz MI = 0,61	MB injected in mice bearing LNCaP prostate tumor xenograft followed by US application: tumor cell apoptosis + suppression of survivin expression	Specifically target PC-3 and LNCaP prostate tumor cells; Intra-cellular delivery observed by CM; Delivery of MB by US application; Survivin expression was suppressed in vivo	[32]
Au NP IONP Nano-graphene oxide (NGO)	Au: 6 nm IONP: 10 nm NGO: 22 nm	Th	f = 1 MHz; i = 2 W/cm2;	NP brought into presence of CT26 tumors exposed to US: temperature elevation rates of 12.5%, 20.4%, and 37.5% for IONP, NGO, and AuNP	Temperature increase is more pronounced in the presence than absence of NP	[45]
Liposomes containing Cis-platine	100 nm	Th Di	1 MHz 2 W/cm2 B-mode observation of ND	Inhibition of 4T1 human breast cancer cells growth by ND exposed to US	Release of 63% of Curcumin under US application; Acoustic droplet vaporization	[34]
Liposomes containing Cis-platin	NA	Th	20 kHz	Treatment of mice bearing C26 footpad murine tumors with NM + US results in negligible tumor growth one moth following treatment compared with untreated mice	Increase in local Cisplatin concentration in C26 footpad murine tumor following NM administration + US application to 70% in US treated tumors compared with 3% in untreated tumors	[35]
DPP-TPA NP	100 nm	Di	Use of a Nexus128 small animal PA imaging system with 680 nm laser (1 W/cm2)	PA of xenografted tumors filled with NP	Increase of PA signal with increasing NP concentration	[156]
NB associated with siRNA (NB-siRNA)	625 nm	Th	f = 1 MHz; i = 0.88 W/cm2;	Mice bearing U87 GBM tumors injected iv with NB-SiRNA followed by US application: Tumor growth delay (compared with treatment of NB-SiRNA without US)	NB can accumulate in intercellular spaces (due to their nm size); “Sonoporation” produced by UTD: increase cell membrane permeability; NB exposed to US: improve siRNA transfection and silencing of targeted genes;	[24]
Hollow mesoporous organosilica NP functionalized with fluorocarbon chains + IR780 (SS) + O2	180 nm	Th	f = 1 MHz I = 1 W/cm2	Destruction of PANC-1 cells in vitro; Shrinkage of hypoxic PANC-1 pancreatic subcutaneous mouse tumors in vivo	NP delivers O2 to tumors and reduces tomor hypoxia Production of ROS to destroy tumors	[42]
Theranostic polymer microcapsules composed of hydrogen-bonded multilayers of tannic acid and poly(N-vinylpyrrolidone) loaded with DOX	5 µm	Th Dia	1/Diagnostic US: f = 2 MHz, i = 115 mW/cm2; 2/ Therapeutic US: f = 20 kHz, i = 15–257 W/cm2	50% DOX release from NM exposed to US → 97% destruction of MCF-7 human cancer cells in vitro (no cytotoxicity without US application) Capsules can be imaged under B-mode US	1/low intensity diagnostic US → 20–30% DOX release from NM 2/high intensity therapeutic US → up to 75% DOX release from NM	[65]
MB with Porphyrin Grafted Lipid (PGL) +  Camptothecin-Floxuridine Conjugate (CF)	0,5–9 µm (MB) 30–100 nm (NB)	Th Dia	f = 1–7 MHz; i = 1 W/cm2; MI < 0.06	MB + ultrasound + laser leads to 90% tumor inhibition rate of HT-29 colorectal cancer with no recurrence in vivo	Transformation of MB into NB under US application produces accumulation of chemo-drugs/photosensitizer in tumors due to enhanced EPR effect PDT (laser) leads to reduction of (ATP)-binding cassette subfamily G member 2 (ABCG2) expression responsible for the drug resistance in chemotherapy	[162]
MB containing a core of PFP-Oxygen and a shell of PLGA loaded with ICG and PTX	150 nm (before laser irradiation) 700 nm (after laser irradiation)	Th Di	f = 1 MHz I = 1 W/cm2	MB exposed to laser + US: apoptosis of SKOV3 cells in vitro + SKOV3 tumor growth inhibition in vivo  → MB can be monitored by US/PA and guided towards tumors	MB release PTX and generate ROS under laser and US exposure MB increase US contrast and improve PA imaging;	[163, 164]
MnOx/TiO-Graphene-polyvinylpyrrolidone Nanocomposite	260 nm	Th Di	f = 1 MHz; I = 1–1.5 W/cm2;	Complete eradication of 4T1 subcutaneous mouse tumors without re-occurrence following NM injection and US + laser administration; (60 °C during 600 s reached during treatment)	Association of TiO2 and graphene prevents electron/hole recombination upon US application and facilitates ROS generation; MnOx enables T1-weighted MRI	[64]
Hydrophilized Au-TiO2 nanocomposites	200 nm	Th	NA	Mice bearing SCC7 tumor injected iv with Au-TiO2 nanocomposites and exposed to US → ROS production + tumor suppression	Combination of TiO2 with Au improves ROS generation by TiO2	[51]
Au NP	15 nm	Th	HIFU i = 10–20 W; f = 1.2 MHz;	For US intensity of 10 W, the maximum temperature rise increased by 32% and 43% for Au NPs concentrations of 0.0625% and 0.125%, compared with the heating without NP; For US intensity of 20 W the lesion volume doubled and tripled for Au concentrations of 0.0625% and 0.125% compared with the heated volume without NP	Application of US in the presence of Au NP:larger temperature increase and larger heated volume than in the absence of NP	[46]
NB conjugated with folate (FOL)	287 nm	Th Di	f = 9 MHz; MI = 0.12;	MCF-7 over-expressing FR: enhanced targeting of NB and better US imaging;	Greater cellular targeting ability for (FOL)-NB than for non targeted NB	[25]
Naturally occuring heme-based pigment biliverdin NP	100 nm	Di	Photoacoustic imaging with Endra Nexus 128 photoacoustic tomographer (excitation between 680 and 800 nm)	NP injected in mouse leg: Detection of NP in lymph nodes using PA	NP strong absorbance at 365 and 680 nm. Excitation in near-infrared: PA signal Excitation in UV: fluorescence	[55]
PFP/C9F17-PAsp(DET)/CAD/PGA-g-mPEG ND	400 nm	Th Di	Di: 3.5 MHz, MI = 0.08;	Increased ND internalization in HepG2 and CT-26 cells following US application	ND: i) contrast agent in US imaging, ii) can release DOX at acidic pH, iii) efficient carrier due to cationic amphiphilic fluorinated polymer	[28, 29, 52]
Oxygen-deficient bimetallic oxide MnWOX NP	6 nm	Th Di	f = 40 kHz; i = 3 W/cm2;	iv/it injection of NP in 4T1-tumor bearing mice → tumor growth retardation; NP metabolized without long-term toxicity	NP stable, biocompatible, produce more ROS than protoporphyrin IX and titanium dioxide, (MnWOX traps electrons/prevents electron–hole recombination	[28, 29, 52]
Outer membrane vesicles (OMV) encapsulating biopolymer melanine	100 nm	Di	f = 5 MHz	It administration of OMV in subcutaneous 4T1 mouse tumors followed by laser irradiation (1.5 W/cm2, 800 nm, 6 min) → tumor disappearance	OMV produces heat under laser irradiation that can be used to destroy tumors and for PA imaging	[57]
PLGA-R837/PLGA-MPLA NP	100 nm	Th	HIFU (f = 4 MHz; i = 43 W)	Colorectal tumors (CT26) grown on both mouse flanks; tumor on one flank removed with HIFU therapy to remove the larger tumor; 40 days after treatment, NP injected and second tumor disappears	R-837/MPLA: agonists of TLR7/TRL4 HIFU → produces tumor antigen; NP → adjuvants stimulating immature DC and naive T cells at tumor sites and tumor-draining lymph nodes	[10]
Liquid perfluorocarbon (PFC) NP conjugated to 9E5 (antibody targeting epiregulin)	140 nm	Th	f = 5 MHz; Peak negative pressure = 1.5 MPa	NPs target 97.8% of EREG expressing cancer cells and kill 57% of those cells following US application; intracellular vaporization changes cell morphology;	Liquid PFC transformed in gas following US exposure; NPs conjugated to 9E5 selectively internalize in cancer cells; kill these cells by US-induced intracellular vaporization	[74]
DOX loaded human serum albumin NP attached at the surface of Chlorin e6 encapsulated MB	2500 nm	Th	f = 1 MHz; i = 0,2 W/cm2	NP/MB + US treatment reduces the number of cells with cancer stem-like cell property	Maximize anticancer efficiency by overcoming MDR NP/MB complex delivered to cells by sonoporation caused by MB cavitation ROS generated by intracellular delivered Ce6 under laser irradiation stops ABCG2 efflux receptor activity overexpressed in doxorubicin-resistant breast cancer cells (MCF-7/ADR), leading to improved chemotherapy efficacy	[36, 37, 38]
Membrane fusogenic liposomes loaded with Docetaxel (MFL-DCT)	100 nm	Th	f = 1.1 MHz; i = 20 W; focused	Mice bearing MDA-MB-231 tumors treated by iv injection of DTX-MFLs + MB followed by US application → tumor growth retardation	MFL-DCT can fuse with cell membrane and thereby efficiently deliver DCT inside cells;	[36–38]
pH-sensitive reduced albumin NP loaded with DOX	146 nm	Th	f = 1.1 MHz; i = 20 W; focused	Mice bearing MDA-MB 231 breast tumors injected with NP and treated by US: Tumor growth retaradation	Application of US improves the efficacy of EPR effect and the diffusion of NP in the tumor	[36–38]
Gaz vesicles (GV): gas-filled protein-shelled NC (produced intracellularly by certain bacteria/archaea	140–800 nm	Di	Imaging at 6 MHz (peak positive pressure of 0.3–1.2 MPa)	In vivo ultrasound imaging during passage through the inferior vena cava (IVC) in mice	US imaging of gas vesicles that can be genetically engineered	[58, 59]
Polymeric (poly(D,L-lactide-co-glycolide) NP containing calcium carbonate, where NP are bound to rabies virus glycoprotein (RVG) peptide (a targeting moiety to neuroblastoma)	220 nm	Di Th	f = 15 MHz (imaging);	Iv injection of NP in mice bearing N2a (neuroblastoma) tumors; NP accumulate at tumor site, NP increase US signals, NP reduce tumor growth	NPs produce carbon dioxide bubbles under acidic conditions (pH change) and enhance US signals NPs generating gas induces necrosis and reduces tumor growth	[169]
H2O2 encapsulated in Fe3O4-PLGA polymersomes	412 nm	Th Di	f = 40 MHz	Mice bearing HeLa tumors injected iv with polymersomes followed by US exposure display tumor disappearance	O2 is used as echogenic source for US imaing; OH production through the Fenton reaction by reaction of H2O2 and Fe3O4	[60]
Long-circulating lipid-coated MB	1500 nm	Di	f = 2.8 MHz	Mice bearing liver tumors injected with MB and SonoVue and imaged with US, MB stay in tumors longer than SonoVue and hence enable US contrast imaging for longer time	MB fabricated by changing the core of SonoVue microbubbles to a higher–molecular weight gas (C3F8) MB have smaller diameter and higher inertial cavitation threshold than Sonovue: better/longer organ imaging	[206, 207]
Liposomes co-encapsulating doxorubicin (DOX), hollow gold nanospheres (HAuNS), and perfluorocarbon (PFC)	200 nm	Th Di	f = 1.9 MHz	Mice bearing 4T1tumors injected iv with liposomes and tumors heated by laser irradiation (2 W/cm2); US signal detected in tumors; treatment leads to DOX release and increase of tumor temperature to 70 °C; tumor growth retardation	Heating of HAuNS by 808 nm NIR laser irradiation; Liposome tumor accumulation due to their nm sizes; Heating triggers DOX release; Gasification of PFC enhances US imaging signal;	[39]
Pt-CuS Janus NM composed of Pt and CuS with inner cavities loaded with sonosensitizers (tetra-(4-aminophenyl) porphyrin, TAPP)	285 nm	Th Di	f = 1 MHz i = 1 W/cm2	Mice bearing CT26 xenograft tumors treated by NM iv administration followed by 808 nm laser irradiation and US Almost complete tumor resection without obvious reoccurrence (heat at 70 °C); Photoacoustic (PA) imaging and NIR thermal imaging	Pt enhances photothermal performance Pt leads to nanozyme activity for transforming H2O2 to O2 and overcome tumor hypoxia NM leads to ROS production	[72]
MON@C: Mesoporous organo-silica nanoparticles (MON) containing catalases (c) inserted inside pores	150 nm	Th	f = 1.1–3.5 MHz; i = 70–100 W;	Nude mice bearing MB231 xenograft tumors injected iv with MON@C followed by HIFU: O2 production yields an increase in tumor ablated volume by 10 compared with HIFU treatment with MON (no O2 production)	MON@C transforms H2O2 into oxygen bubbles more efficiently than free catalase Bubbles amplify echo signal to guide HIFU surgery; Bubbles intensify cavitation effect under HIFU irradiations Cancerous region displays larger H2O2 concentration compared to the normal tissue (effect specific to tumor region)	[40, 130]
AML: Liposome containing: i) Anethole Dithiolethione (ADT) and hydrogen sulfide (H2S) pro-drug, embedded in lipid bilayer, ii) SPION in liposome core	166 nm (liposome) 7 nm (MNP)	Th Di	f = 18 MHz; B mode imaging	NB specifically target tumor in vivo following magnetic field application Intra-tumoral conversion of nanostructure to microstructure: better anticancer efficacy Transformation monitored by MRI/US imaging	AML generate intra-tumoral H2S bubbles used for tumor imaging and tumor destruction (gas emission) under HIFU AML exposed to magnetic field: significant inhibition of tumor growth	[40, 43, 130]
NC: GPC3 antibody linked to PEGylated nanometric-reduced-graphene-oxide associated with NB	700 nm	Th	F = 1 MHz; I = 1–3.5 W/cm2	NC inhibit HepG2 cells following US and laser applications	US application leads to NB destruction and an increase in NC concentration around the HepG2 cells Heat at 60 °C by laser irradiation helps to destroy tumor cells	[208]
NB associated with fluorescent dyes	112 nm	Di	F = 4,4 MHz; MI = 0,1	NB: efficient imaging of mouse breast tumor (higher concentration in tumor compared with commercially available US CA agent)	Dyes yield BRET − FRET mechanism and large increase in fluorescent signal NB enables imaging by US of delineation of tissue microvasculature	[26]
EXO-DVDMS: sinoporphyrin sodium (DVDMS), attached to tumor cell-derived exosomes (EXO)	150 nm	Di Th	f = 1 MHz; i = 3 W;	EXO-DVDMS followed by ultrasound applications: growth inhibition of breast cancer-lung metastasis	Exosomes serve as camouflage to enable DVDMS to reach tumor sites; Exosomes target specifically homotypic tumors US is applied to enhance accumulation of EXO-DVDMS is tumors (improved efficacy of EPR effect) EXO-DVDMS endocytosed by lysosomes; low lysosome pH yields DVDMS release and triggers cell death-signaling pathways	[56]
NP: (mPEG-PLGA) associated with anti-carcinoembryonic antigen and anti-carbohydrate antigen 19–9 encapsulating PTX	100 nm	Di Th	f = 1 MHz i = 1 W/cm2 UTMD (ultrasound targeted microbubble destruction)	NP have prolonged imaging time in rabbit kidney and tumor of nude mice compared with Sonovue NP have potential enhanced antitumor effect due to longer tumor residence time	NP internalization facilitated by the application of US	[209]
NC: PLGA NC coated with a thin Silica layer encapsulating i) perfluorocarbon (PFOB), ii) antitumor Ruhenium complex, iii) superparamagnetic Fe3O4 NP	225 nm	Di Th	i = 270 W (HIFU)	HeLa tumor-bearing nude mice injected iv with NC followed by HIFU treatment resulted in more tumor inhibition than HIFU alone	Imaging by US and MRI Image-guided HIFU-triggered chemotherapy PFOB/gas in NC causes collapse of the shell under HIFU and releases Ruhenium complex	[44]
Self-assembled peptide-based NP encasulating phalloidin	300/1200 nm	Di	NA	Internalization in A549 cells of phalloidin into cells following US-triggered rupture of nano-peptisomes	Phalloidin delivered to cell cytoplasm upon US-mediated rupture of nano-peptisomes	[63]
NC: Anti-cancer drug + PFP encapsulated in glycol chitosan NP Hydrophobic core/hydrophilic shell	432 nm	Di Th	i = 0.0676 W/cm2; f = 10 MHz; MI = 0.235;	Mice bearing SCC7 tumors injected IV with NC followed by US application: accumulation in tumor + tumor growth retardation (effect more pronounced than in the absence of US application)	NC echogenic due to MB formation US-triggered drug release Enhanced EPR effect (nanometric size)	[174]
Carbonate NP (pluronic external surface) + inner part: gaz/DTX (chemotherapeutic drug)	100–300 nm	Th Di	f = 10 MHz; MI: 0.235; i: 0.0676 W/cm2	Mice bearing SCC7 tumors injected iv with NC followed by US applications: tumor growth retardation	Generates bubbles under US application; Release drugs under US application;	[137]
MB loaded with porphyrin	NA	NA	F = 1 MHz	Extravasation of MB outside of bllod vessels in vivo under US exposure	Transformation of MB to NB (gaz loss + shell shedding)	[68–70]
TNB: NB linked to NPY (Y1 receptor ligand) + DOX	300 nm	Th	f = 1,5–10 MHz; MI = 0,7;	Mice bearing 4T1 tumors treated by iv injection of TNB + DOX followed by US application: tumor growth retardation;	DOX and TNB are injected separately; US irradiation favors EPR effect of DOX and DOX diffusion in tumor (with better efficacy than MB);	[210]
NC: hollow mesoporous TiO2 surrounded by DsDNA containing DOX	126 nm	Th	i = 1 W/cm2	Mice bearing MCF-7/ADR tumors injected iv with NC followed by US application: tumor growth retardation	Treatment enables to overcome drug resistance towards MCF-7/ADR via the inhibition of mitochondrial energy supply due to the “explosion” of NC Treatment produces ROS and releases DOX NC can escape lysosome following US application;	[50]
ND of PFC stabilized by albumin	160 nm	Th	f = 1 MHz; i = 3.5 W	Mice bearing 4T1 tumors injected iv with ND + liposomal Ce6 followed by laser and US irradiation: Tumor growth delay	NDs adsorb oxygen in lung + release oxygen in tumor under ultrasound stimulation (cycles are repeated); Enhances tumor oxygenation and improves efficacy of PDT/RT treatment of tumors	[30]
ND containing PFC, a photoabsorber/photoacoustic agent (PDI), and a photosensitizers ZnF16Pc	113 nm	Di	f = 40 MHz	ND injected iv in mice bearing U87MG glioblastoma: ND tumor accumulation via EPR effect (imaging of ND via PA/US following laser irradiation at 671 nm) PDT + PTT treatment, result in complete tumor eradication with minimal side effects	Laser irradiation of PDI: liquid-to-gas phase transition of PFC + PTT effect PFC provides O2 to tumor, hence improving PDT efficacy	[31]
Anti-EGFR-PEG-SPIO	9 nm	Th	f = 1–1.2 MHz i = 60–160 W/cm2	Treatment of rats with lung tumors injected with SPIO and exposed to US: tumor growth retardation	SPIO specifically target lung cancer cells overexpressing EGFR SPIO yield more heat in tumors than healthy tissues SPIO improve MRI sensitivity for visualization of EGFR overexpressed lung cancer in a rat model	[48, 49]
NET-1 siRNA-conjugated sub micron bubble (SMB)	600 nm	Th	f = 1 MHz; i = 1 W/cm2	NET-1 siRNA-SMB brought into presence of SMMC-7721 human hepatocellular carcinoma cells followed by low-frequency US application → enhancement of gene transfection efficacy	SMB exposed to low-frequency US promotes gene transfection	[211]
Echogenic NB enclosing cell-permeable peptides (CPPs) and siRNA	200 nm	Th	f = 1 MHz; i = 1 W/cm2	NB brought into presence of human breast tumor cells followed by US application: releases of 90% of encapsulated CPP-siRNA (compared with 1.5% without US) NB administered iv to mice bearing fibrosarcoma HT-1080 tumors: i) NB tumor accumulation, ii) increase in c-myc silencing, iii) tumor growth delay	Local ultrasound stimulation triggered the release of CPP-siRNA from the NBs and activated its tumor cell penetration	[170]
Peptide labeled semimetal bismuth NP (Bi-LyP-1 NP)	3,6 nm	Th Di	PA using a Vevo LAZR PA system	Mice bearing 4T1 tumors injected iv with Bi-LyP-1 NP exposed to laser + X-ray: i) heat at 45 °C during 15–20 min, ii) tumor growth retardation; Bi-LyP-1 NP: cleared from mice through renal/ fecal routes after 30 days	Bi-LyP-1 NP: more tumor accumulation with peptide LyP-1 than without LyP-1; Bi-LyP-1 NP: Absorb both ionizing radiation and the second near-infrared (NIR-II) window laser radiation; Bi-LyP-1 NP: dual mode imaging (CT/PA); Bi-LyP-1 NP: efficient synergistic NIR-II photothermal/radiotherapy of tumors	[53]
Silicon needle covered by Zinc-Oxide nanowires (ZnONW)	MB: 5–20 µm	Th	f = 20 kHz; i = 5 W/cm2;	Mice bearing MC4L2 tumors treated by iv injection of ZnONW followed by US application: ≈82% decrease in tumor size within 10 days compared with 25% with PTX	ZnONW produce MB under US application	[212]
NC: ammonium bicarbonate, gold nanorods and DOX encapsulated in folic acid conjugated liposomes	100–150 nm	Th	f = 1 Hz; i = 1 W;	S180 tumor-bearing mice injected iv with NC followed by laser or US application: tumor growth delay	NC allows: i) multimodal imaging (CT/US), ii) local release of drug (doxorubicin), iii) hyperthermia Ammonium bicarbonate allows controlled DOX release	[6]
NC: terrylenediimide (TDI) poly(acrylic acid) (TPA) based nanomedicine (TNM)	13 nm	Th Di	NA	4T1 bearing mice administered iv with NC followed by laser irradiation: tumor growth delay	Temperature increase under laser irradiation (up to 60 °C) PA imaging of NC in tumor	[213]
Polymersome embedding perfluorocarbon and DOX;	178–437 nm	Th Di	f = 1 MHz Acoustic pressure: 2 Mpa	Mice bearing C6 glioma tumors injected iv with NC and exposed to US: tumor growth retardation	Size of NC increases from 178 nm during circulation to 437 nm in acidic tumor microenvironment NC small size allows efficient tumor uptake NC swells at tumor size to become efficient CA for US imaging; NC release DOX in tumor under US application	[61, 62]
Biomimetic nano-system (BM): Macrophage membrane coated on CAu-BMSN: CORM-401 (H2O2-sensitive CO release prodrug) loaded into Au NP associated with black phosphorus quantum dots	50 nm	Th Di	f = 1 MHz; i = 1 W/cm2;	Mice bearing 4T1 tumors injected iv with biomimetic nano-systems followed by US application: tumor growth retardation	BN: tumor-targeted delivery of singlet oxygen (1O2) and carbon monoxide (CO) following US application in presence of H2O2 in tumor microenvironment; Tumor targeting favored by macrophage membrane (RES evasion) Cell apoptosis caused by mitochondrial dysfunction Effective immune responses through indoleamin 2,3-dioxygenase (IDO) signal blocking (prevents tumor regrowth and metastasis)	[75, 135]
Annexin V-conjugated NB (A-NB)	635 nm	Th Di	f = 10–60 MHz	Long lasting US imaging of NC in MDA-MB-231 mouse tumors	A-NB: extravasate in tumor vasculature and recognize apoptotic tumor cells A-NB: better tumor US contrast than non targeted NB	[214]
NC: MnOx with biocompatible/biodegradable hollow mesoporous organosilica NP conjugated with protoporphyrin (sonosensitizer) and cyclic arginine-glycine-aspartic pentapeptide (targeting peptide)	100 nm	Th Di	f = 1 MHz i = 1.5 W/cm2	Mice bearing U87 tumor xenograft injected iv with NC followed by US application: suppressed tumor growth NC can be imaged by MRI in tumor, enabling therapeutic guidance/monitoring during SDT	MnOx: i) nanoenzyme converting H2O2 (overexpressed in tumor) into oxygen, ii) increasing tumor oxygen level, iii) facilitating ROS production, iv) improving SDT efficacy	[71]

CA, contrast agents; CAV, Commercially available; CM, confocal microscopy; CT, computed tomography; DOX, Doxorubicin; ICG, Indocyanine green; MNP, magnetic nanoparticle; MB, Microbubbles; MI, Micelles

MNC, Magnetic nanocapsule; MPLA, monophosphoryl lipid A; NM, Nanomaterial; NB, Nanobubbles; NC, Nanocapsule; ND, Nanodroplet; NM, Nanomaterials; OMV, Outer membrane vesicle; PA, Photoacoustic; PFP, Perfuoropentane; PLGA, poly(lactic-co-glycolic acid); PTT, Photothermal therapy; PTX, paclitaxel; SPION, Superparamagnetic iron oxide nanoparticles; SS, Sonosensitizer; TPA, Two photon absorption; US, Ultrasound; XIAP, X-linked inhibitor of apoptosis protein