Therapeutic oxygen delivery by perfluorocarbon-based colloids

After the protocol-related indecisive clinical trial of Oxygent, a perfluorooctylbromide/ phospholipid nanoemulsion, in cardiac surgery, that often unduly assigned the observed untoward effects to the product, the development of perfluorocarbon (PFC)-based O-2 nanoemulsions (blood substitutes) has come to a low. Yet, significant further demonstrations of PFCO2-delivery efficacy have continuously been reported, such as relief of hypoxia after myocardial infarction or stroke; protection of vital organs during surgery; potentiation of O-2-dependent cancer therapies, including radio-, photodynamic-, chemo- and immunotherapies; regeneration of damaged nerve, bone or cartilage; preservation of organ grafts destined for transplantation; and control of gas supply in tissue engineering and biotechnological productions. PFC colloids capable of augmenting O-2 delivery include primarily injectable PFC nanoemulsions, microbubbles and phase-shift nanoemulsions. Careful selection of PFC and other colloid components is critical. The basics of O-2 delivery by PFC nanoemulsions will be briefly reminded. Improved knowledge of O-2 delivery mechanisms has been acquired. Advanced, size-adjustable O-2-delivering nanoemulsions have been designed that have extended room-temperature shelf-stability. Alternate O-2 delivery options are being investigated that rely on injectable PFC-stabilized microbubbles or phaseshift PFC nanoemulsions. The latter combine prolonged circulation in the vasculature, capacity for penetrating tumor tissues, and acute responsiveness to ultrasound and other external stimuli. Progress in microbubble and phase-shift emulsion engineering, control of phase-shift activation (vaporization), understanding and control of bubble/ultrasound/tissue interactions is discussed. Control of the phase-shift event and ofmicrobubble size require utmost attention. Further PFC-based colloidal systems, including polymeric micelles, PFC-loaded organic or inorganic nanoparticles and scaffolds, have been devised that also carry substantial amounts of O-2. Local, on-demand O-2 delivery can be triggered by external stimuli, including focused ultrasound irradiation or tumor microenvironment. PFC colloid functionalization and targeting can help adjust their properties for specific indications, augment their efficacy, improve safety profiles, and expand the range of their indications. Many new medical and biotechnological applications involving fluorinated colloids are being assessed, including in the clinic. Further uses of PFC-based colloidal nanotherapeuticswill be brieflymentioned that concern contrast diagnostic imaging, includingmolecular imaging and immune cell tracking; controlled delivery of therapeutic energy, as for noninvasive surgical ablation and sonothrombolysis; and delivery of drugs and genes, including across the blood-brain barrier. Evenwhen the fluorinated colloids investigated are designed for other purposes than O-2 supply, they will inevitably also carry and deliver a certain amount of O-2, and may thus be considered for O-2 delivery or co-delivery applications. Conversely, O-2-carrying PFC nanoemulsions possess by nature a unique aptitude for F-19 MR imaging, and hence, cell tracking, while PFC-stabilized microbubbles are ideal resonators for ultrasound contrast imaging and can undergo precise manipulation and on-demand destruction by ultrasound waves, thereby opening multiple theranostic opportunities. (C) 2021 Published by Elsevier B.V.

Automated summary

PFC-based O-2 nanoemulsions have shown efficacy in various medical applications, such as relieving hypoxia, protecting vital organs, enhancing cancer therapies, and promoting tissue regeneration. Advanced nanoemulsions with improved O-2 delivery mechanisms and stability have been designed, offering new possibilities in medical and biotechnological applications. Additional uses of PFC-based colloidal nanotherapeutics are being explored, including contrast diagnostic imaging, therapeutic energy delivery, and drug administration, expanding their potential in the medical field.