Ultrasound-activated decafluoropentane-cored and chitosan-shelled nanodroplets for oxygen delivery to hypoxic cutaneous tissues

Magnetto, C.; Prato, Maurizio; Khadjavi, Amina; Giribaldi, Giuliana; Fenoglio, Ivana; Jose, Jithin; Gulino, Giulia Rossana; Cavallo, Federica; Quaglino, Elena; Benintende, Emilio; Varetto, Gianfranco; Troia, Adriano; Cavalli, Roberta; Guiot, Caterina

doi:10.1039/c4ra03524k

Cited by 42 publications

(103 citation statements)

References 61 publications

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“…The same nanoconstruct was studied to deliver oxygen to hypoxic tissues, exploiting the boiling point of the perfluoropentane core (32°C). In fact, whereas this compound is liquid at room temperature, it is in vapour phase at body temperature, leading [155][156][157][158][159][160][161][162][163][164][165][166][167][168][169][170][171][172] to an higher expansion of the nanobubbles and enhancing the release of loaded oxygen molecules under ultrasound irradiation [102]. In addition to liposomes and polymeric NPs, also metallic and inorganic nanoconstructs could represent efficient platforms for carrying sonosensitizer molecules.…”

Section: Nps Used In the Sonodynamic Therapymentioning

confidence: 99%

Nanoparticle-assisted ultrasound: A special focus on sonodynamic therapy against cancer

Canavese

Ancona

Racca

et al. 2018

Chemical Engineering Journal

327

247

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• Ultrasound-based therapies are opening new horizons in the oncological field.• Innovative and promising solutions derive from different nanoparticles-assisted ultrasound treatments.• Sonodynamic therapy (SDT) emerged recently as a novel approach for cancer treatment.• Different and complex cell death mechanisms are involved in nanoparticles-assisted SDT.• Nanoparticles-assisted ultrasound is still at its infancy in clinics. A R T I C L E I N F O Keywords:Inertial cavitation Reactive oxygen species Sonoluminescence Sonodynamic Tumor Therapy Cytotoxicity A B S T R A C TAt present, ultrasound radiation is broadly employed in medicine for both diagnostic and therapeutic purposes at various frequencies and intensities. In this review article, we focus on therapeutically-active nanoparticles (NPs) when stimulated by ultrasound. We first introduce the different ultrasound-based therapies with special attention to the techniques involved in the oncological field, then we summarize the different NPs used, ranging from soft materials, like liposomes or micro/nano-bubbles, to metal and metal oxide NPs. We therefore focus on the sonodynamic therapy and on the possible working mechanisms under debate of NPs-assisted sonodynamic treatments. We support the idea that various, complex and synergistics physical-chemical processes take place during acoustic cavitation and NP activation. Different mechanisms are therefore responsible for the final cancer cell death and strongly depends not only on the type and structure of NPs or nanocarriers, but also on the way they interact with the ultrasonic pressure waves. We conclude with a brief overview of the clinical applications of the various ultrasound therapies and the related use of NPs-assisted ultrasound in clinics, showing that this very innovative and promising approach is however still at its infancy in the clinical cancer treatment.

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Section: Nps Used In the Sonodynamic Therapymentioning

confidence: 99%

Nanoparticle-assisted ultrasound: A special focus on sonodynamic therapy against cancer

Canavese

Ancona

Racca

et al. 2018

Chemical Engineering Journal

327

247

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“…The known benefits of nanotechnology, including size, stability, and controlled drug release (Schroeter et al, 2010), combined with the emerging advantages of ultrasound (US)-triggered transdermal drug delivery (Park et al, 2014) have paved the way to develop nonconventional and innovative therapies for infected chronic wounds. In particular, USresponsive perfluoropentane-cored oxygen-loaded nanobubbles and decafluoropentane (DFP)-cored oxygen-loaded nanodroplets (OLNs), both coated with biocompatible and biodegradable polysaccharides such as chitosan or dextran, recently proved effective in releasing oxygen either in vitro or in vivo (Cavalli et al, 2009a(Cavalli et al, , 2009bMagnetto et al, 2014;Prato et al, 2015).…”

Section: Contents Lists Available At Sciencedirectmentioning

confidence: 99%

Chitosan-shelled oxygen-loaded nanodroplets abrogate hypoxia dysregulation of human keratinocyte gelatinases and inhibitors: New insights for chronic wound healing

Khadjavi

Magnetto

Panariti

et al. 2015

Toxicology and Applied Pharmacology

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“…For OFN and OSS PBS formulations, OLN preparation protocol was 208 applied omitting O 2 or dextran/DFP addition, respectively. Immediately after manufacturing, 209 nanodroplets were sterilized through ultraviolet (UV)-C ray exposure for 20 min and 210 characterized for: morphology and shell thickness, by optical and transmitting electron 211 microscopy; size, particle size distribution, polydispersity index and zeta potential, by 212 dynamic light scattering; refractive index by polarizing microscopy; viscosity and shell shear 213 modulus by rheometry; and oxygen content (before and after UV-C sterilization) through a 214 chemical assay as previously described [Magnetto et al, 2014;Prato et al, 2015]. O 2 ) conditions, in a humidified CO 2 /air-incubator at 37°C in serum-free medium.…”

mentioning

confidence: 99%

Dextran-shelled oxygen-loaded nanodroplets reestablish a normoxia-like pro-angiogenic phenotype and behavior in hypoxic human dermal microvascular endothelium

Basilico

Magnetto

D’Alessandro

et al. 2015

Toxicology and Applied Pharmacology

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When citing, please refer to the published version. MMP-9 and increases TIMP-1 without affecting TIMP-2 secretion, whereas in human 60 keratinocytes it reduces MMP-2, MMP-9, and TIMP-2, without affecting TIMP-1 release. 61Provided that the phenotype of the cellular environment is better understood, chronic wounds 62 might be targeted by new oxygenating compounds such as chitosan-or dextran-shelled and 63 2H,3H-decafluoropentane-cored oxygen-loaded nanodroplets (OLNs). Here, we investigated 64 the effects of hypoxia and dextran-shelled OLNs on the pro-angiogenic phenotype and 65 behavior of human dermal microvascular endothelium (HMEC-1 cell line), another cell 66 population playing key roles during wound healing. Normoxic HMEC-1 constitutively 67 released MMP-2, TIMP-1 and TIMP-2 proteins, but not MMP-9. Hypoxia enhanced MMP-2 68 and reduced TIMP-1 secretion, without affecting TIMP-2 levels, and compromised cell 69 ability to migrate and invade the extracellular matrix. When taken up by HMEC-1, nontoxic 70OLNs abrogated the effects of hypoxia, restoring normoxic MMP/TIMP levels and 71 promoting cell migration, matrix invasion, and formation of microvessels. These effects were 72 specifically dependent on time-sustained oxygen diffusion from OLN core, since they were 73 not achieved by oxygen-free nanodroplets or oxygen-saturated solution. Collectively, these 74 data provide new information on the effects of hypoxia on dermal endothelium and support 75 the hypothesis that OLNs might be used as effective adjuvant tools to promote chronic wound 76 healing processes. 77 78Keywords: oxygen; nanodroplet; matrix metalloproteinase (MMP); tissue inhibitor of 79 metalloproteinase (TIMP); human microvascular endothelial cell (HMEC); skin. 80 5 Introduction 81 82After injury, skin integrity must be restored promptly to reestablish the homeostatic 83 mechanisms, minimize fluid loss, and prevent infection [Greaves et al., 2013]. This is 84 achieved through wound healing, a complex biological process where multiple pathways are 85 simultaneously activated to induce tissue repair and regeneration. Traditionally, acute wound 86 healing is defined as a complex multi-step and multi-cellular process, distinguished in four 87 phases involving different cell types: i) hemostasis, involving platelets; ii) inflammation, 88 involving neutrophils, monocytes, and macrophages; iii) proliferation, involving 89 keratinocytes, endothelial cells, and fibroblasts; and iv) matrix remodeling, involving 90 keratinocytes, myofibroblasts, and endothelial cells. [Diegelmann et al., 2004]. In particular, 91 during the third and fourth phases, the endothelium plays a pivotal role, since wound 92 microvasculature is rebuilt through angiogenesis to restore the supply of oxygen, blood 93 constituents and nutrients to the regenerating tissue, helping to promote fibroplasia and 94 prevent sustained tissue hypoxia [Eming et al., 2014]. Notably, oxygen represents a key 95 regulator of normal wound healing since it is required for collagen deposition, 96 epith...

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Ultrasound-activated decafluoropentane-cored and chitosan-shelled nanodroplets for oxygen delivery to hypoxic cutaneous tissues

Abstract: Ultrasound-activated decafluoropentane/chitosan nanodroplets effectively release oxygen to the skin.

Cited by 42 publications

References 61 publications

Nanoparticle-assisted ultrasound: A special focus on sonodynamic therapy against cancer

Nanoparticle-assisted ultrasound: A special focus on sonodynamic therapy against cancer

Chitosan-shelled oxygen-loaded nanodroplets abrogate hypoxia dysregulation of human keratinocyte gelatinases and inhibitors: New insights for chronic wound healing

Dextran-shelled oxygen-loaded nanodroplets reestablish a normoxia-like pro-angiogenic phenotype and behavior in hypoxic human dermal microvascular endothelium

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