Table 3 Summary of the development of nano-systems for the treatment of vascular anomalies

Liposomal gel

Propranolol hydrochloride

Transdermal drug delivery

–

Hemangiomas

Increase drug content in skin obviously, reduce dosing frequency compared with suspension, decrease drug content in the systemic circulation

[153]

Polymeric film

Propranolol hydrochloride

Transdermal drug delivery

–

Hemangiomas

Enhance skin retention, increases skin permeation ability

[126]

Cubic nanoparticles (CNPs)

Propranolol hydrochloride

Transdermal drug delivery

–

Hemangiomas

Improved drug transportation across, enhance skin retention with a decrease in the size of CNPs, possess favorable stability during storage

[127]

Lipid polymer nanoparticles

Rapamycin

Intravenous route

Anti-VEGFR2 antibody

Hemangiomas

Released rapamycin lastingly, and inhibiting hemangiomas both in vitro and in vivo

[154]

Poly(lactic-co-glycolic acid) (PLGA) nanoparticles

Propranolol

Intravenous route

Anti-VEGFR antibody

Hemangiomas

Anti-VEGFR antibody has a great targeted ability in HemECs and HUVECs

[25]

Polymer–lipid hybrid nanoparticles

Rapamycin

Intravenous route

–

Hemangiomas

Sustained release of rapamycin, and significantly reduced the frequency of administration

[155]

Exosome-mimetic nanoparticles-in-PLGA microspheres

Rapamycin

Intravenous route

–

Hemangiomas

Sustained release, efficient delivery, and therapeutic

efficacy of rapamycin towards hemangiomas

[139]

Liposomes-in-microsphere (LIM)

Propranolol

Intravenous route

–

Hemangiomas

Promising approach to efficiently and locally deliver propranolol to the hemangioma, significant inhibit the infantile hemangioma

[156]

Poly(lactic-co-glycolic acid) (PLGA) nanoparticles

Propranolol

Intravenous route

CD133 aptamers

Hemangiomas

Significantly reduced the frequency of administration of propranolol and excellent targeted ability

[24]

Mesoporous silica nanoparticles(MSN)

Propranolol

Intravenous route

–

Hemangiomas

PRN@MSN inhibited the growth of hemangiomas both in vitro and in vivo and induced autophagy dysfunction with excessive autophagosome accumulation

[143]

Poly(ethylene oxide)–poly(d,l-lactic acid) (PEG-PLA)block copolymer

–

Intravenous route

Cell-penetrating peptide (CPP)

Vascular anomalies (human vascular networks)

Phototargeted NP can enhance accumulation of the NP and drug in a subcutaneous graft model of engineered vessels

[157]

Liposomes

Sodium morrhuate

Intravenous route

Anti-VEGFR2/KDR antibody

Hemangioma

KDR-targeting sodium morrhuate immunoliposomes have an increased capacity for binding to HECs and elicit apoptotic death through the mitochondrial apoptotic cascade

[158]

Gold nanoshells (AuNSs)

–

Intravenous route (photo-assist)

–

Venous malformation

Intravenously administered of AuNSs and then exposure by 808 nm NIR iodine laser can ablate venous malformations

[147]

Gold nanorods (GNRs)

–

Intravenous route (photo-assist)

CD31 antibody

Venous malformation

Anti-CD31 GNRs could be applied specifically to treat venous malformations and exhibited effective ablation of PTT both in vitro and in vivo

[148]