Electrospraying as a Technique for the Controlled Synthesis of Biocompatible PLGA@Ag2S and PLGA@Ag2S@SPION Nanocarriers with Drug Release Capability.

Alexis Alvear-Jiménez,Consolación Melguizo,Laura Lozano-Chamizo,Beatriz Garcia-Pinel,Gonzalo Villaverde,Pablo Guardia,Marco Filice,Rafael Contreras-Cáceres,Yingli Shen,Irene Zabala Gutierrez,Miguel Tinoco,José Prados,Daniel Jaque,Manuel López-Romero

doi:10.3390/pharmaceutics14010214

Abstract

Ag2S nanoparticles are near-infrared (NIR) probes providing emission in a specific spectral range (~1200 nm), and superparamagnetic iron oxide nanoparticles (SPION) are colloidal systems able to respond to an external magnetic field. A disadvantage of Ag2S NPs is the attenuated luminescent properties are reduced in aqueous media and human fluids. Concerning SPION, the main drawback is the generation of undesirable clusters that reduce particle stability. Here, we fabricate biocompatible hybrid nanosystems combining Ag2S NPs and SPION by the electrospraying technique for drug delivery purposes. These nanostructures are composed of poly(lactic-co-glycolic acid) (PLGA) as the polymeric matrix in connection with both Ag2S NPs and SPIONs. Initially, we fabricate a hybrid colloidal nanosystem composed of Ag2S NPs in connection with PLGA (PLGA@Ag2S) by three different routes, showing good photoluminescent (PL) properties with relatively high average decay times. Then, we incorporate SPIONs, obtaining a PLGA polymeric matrix containing both Ag2S NPs and SPION (PLGA@Ag2S@SPION). Interestingly, in this hybrid system, the location of Ag2S NPs and SPIONs depends on the synthesis route performed during electrospraying. After a detailed characterization, we demonstrate the encapsulation and release capabilities, obtaining the kinetic release using a model chemotherapeutic drug (maslinic acid). Finally, we perform in vitro cytotoxicity assays using drug-loaded hybrid systems against several tumor cell lines.

Highlights

Fluorescence optical imaging has emerged as a technique used in nanomedicine to obtain physiological information of organs and tissues [1]
To obtain NPs able to be dispersed in biological media, the Ag2 S@DDT NPs were functionalized with SH-PEG-OCH3 by ligand exchange process, removing the DDT moieties and exchanging them with the PEG units
The hybrids systems were initially structured by poly(lactic-co-glycolic acid) (PLGA) as a biocompatible polymer in connection with PL Ag2 S NPs

Summary

Introduction

Fluorescence optical imaging has emerged as a technique used in nanomedicine to obtain physiological information of organs and tissues [1]. Several fluorophores emitting in the visible (Vis, 400–750 nm) or the first near-infrared window (NIR-I, 750–900 nm) have been synthesized as emitting markers [2–4]. The main disadvantages of these types of fluorophores are: (i) low tissue penetration, (ii) reduced spatial resolution, (iii) long acquisition times, and (iv) the autofluorescence generated by living tissues [5], which generates unclear images [6]. Fluorophores emitting in the second near-infrared window (NIR-II, 1000–1400 nm) have been successfully fabricated as a luminescence alternative for in vivo applications [7–9]. The principal advantages of NIR-II systems are that (i) they reduce photon scattering, (ii) they provide deeper tissue penetration, and (iii) they generate a much lower autofluorescence [10]. Silver sulfide nanoparticles (Ag2 S NPs) have recently appeared as a new type of NIR-II fluorophores [11,12], exhibiting fluorescence emission at

Methods

Results

Conclusion