Abstract
In the present study, we examined properties of poly(lactide-co-glycolide) (PLGA)-based nanocarriers (NCs) with various functional or “smart” properties, i.e., coated with PLGA, polyethylene glycolated PLGA (PEG-PLGA), or folic acid-functionalized PLGA (FA-PLGA). NCs were obtained by double emulsion (water-in-oil-in-water) evaporation process, which is one of the most suitable approaches in nanoemulsion structural design. Nanoemulsion surface engineering allowed us to co-encapsulate a hydrophobic porphyrin photosensitizing dye—verteporfin (VP) in combination with low-dose cisplatin (CisPt)—a hydrophilic cytostatic drug. The composition was tested as a multifunctional and synergistic hybrid agent for bioimaging and anticancer treatment assisted by electroporation on human ovarian cancer SKOV-3 and control hamster ovarian fibroblastoid CHO-K1 cell lines. The diameter of PLGA NCs with different coatings was on average 200 nm, as shown by dynamic light scattering, transmission electron microscopy, and atomic force microscopy. We analyzed the effect of the nanocarrier charge and the polymeric shield variation on the colloidal stability using microelectrophoretic and turbidimetric methods. The cellular internalization and anticancer activity following the electro-photodynamic treatment (EP-PDT) were assessed with confocal microscopy and flow cytometry. Our data show that functionalized PLGA NCs are biocompatible and enable efficient delivery of the hybrid cargo to cancer cells, followed by enhanced killing of cells when supported by EP-PDT.
Highlights
Effective nanocarriers (NCs) for cancer treatment need both passive and active targeting approaches to achieve highly specific drug delivery to cancer cells while avoiding rapid clearance by the mononuclear phagocyte system and cytotoxicity to normal cells [1]
Biodegradable polyesters, such as poly(glycolic acid) (PGA), poly(lactic acid) (PLA), and their copolymers are the favorite synthetic polymers for biomedical and pharmaceutical applications, since they were proved to be useful in the stabilization of different drug delivery systems and have excellent biocompatibility and bioresorbability [25]
According to the first phase of our general strategy presented in Scheme 1a, poly(lactic-co-glycolic acid) (PLGA), polyethylene glycol (PEG)-PLGA, and functionalized PLGA (FA-PLGA) polymers were used for stabilization and structuration of nanoemulsion droplets involving the three-step w/o/w double emulsion evaporation approach, leading to co-encapsulation of the hybrid cargo, i.e., VP and CisPt in the NC’s double compartment
Summary
Effective nanocarriers (NCs) for cancer treatment need both passive and active targeting approaches to achieve highly specific drug delivery to cancer cells while avoiding rapid clearance by the mononuclear phagocyte system and cytotoxicity to normal cells [1]. Nanoemulsion systems (so-called submicron emulsions, parenteral emulsions, or miniemulsions) are referred to in the literature as transparent or translucent (often bluish) isotropic dispersions of water and oil, with nano-domains coexisting in high kinetic equilibrium due to the occurrence of surfactant molecules at the oil/water interface [2,3] Owing to their small size (usually in the range 20–200 nm), high kinetic stability, and much lower surfactant concentration (typically 3–10%) required for their formation in comparison to microemulsions (generally about 20% and higher, both oil-in-water (o/w) and water-in-oil (w/o), nanoemulsions were found to be very attractive for droplet engineering to obtain efficient nanocarriers with functional properties. The biological effectiveness of such multifunctional nanosystems in the combined anticancer therapy may be intensified by increasing their cellular uptake by the electroporation (EP) approach
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