Abstract

In this study, we employed the copolymer poly(methyl vinyl ether-alt-maleic monoethyl ester) (PMVEMA-Es) and three fluorene-based cationic conjugated polyelectrolytes to develop fluorescent nanoparticles with emission in the blue, green and red spectral regions. The size, Zeta Potential, polydispersity, morphology, time-stability and fluorescent properties of these nanoparticles were characterized, as well as the nature of the interaction between both PMVEMA-Es and fluorescent polyelectrolytes. Because PMVEMA-Es contains a carboxylic acid group in its structure, the effects of pH and ionic strength on the nanoparticles were also evaluated, finding that the size is responsive to pH and ionic strength, largely swelling at physiological pH and returning to their initial size at acidic pHs. Thus, the developed fluorescent nanoparticles can be categorized as pH-sensitive fluorescent nanogels, since they possess the properties of both pH-responsive hydrogels and nanoparticulate systems. Doxorubicin (DOX) was used as a model drug to show the capacity of the blue-emitting nanogels to hold drugs in acidic media and release them at physiological pH, from changes in the fluorescence properties of both nanoparticles and DOX. In addition, preliminary studies by super-resolution confocal microscopy were performed, regarding their potential use as image probes.

Highlights

  • The development of biocompatible nanosystems that integrate increasingly sophisticated functions, such as imaging and therapeutic properties, in one entity is having a high impact in pharmaceutical and biomedical applications, establishing smart nanomedical vehicles with theragnostic applications [1,2,3,4,5]

  • Because the of PMVEMA-Es contains an ionizable acidic group in its structure with a pKa ~5.3, we explored the effect of pH on the new formulations, finding that the nanoparticles have the properties of a reversibly cross-linked system, as their overall size is responsive to pH and ionic strength, swelling at physiological pH and returning to their initial size at acidic pHs

  • Nanoparticles composed of PMVEMA-Es (0.03 M in terms of repeat units) were prepared in water, following the protocol described in Materials and Methods, and subsequently characterized

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Summary

Introduction

The development of biocompatible nanosystems that integrate increasingly sophisticated functions, such as imaging and therapeutic properties, in one entity is having a high impact in pharmaceutical and biomedical applications, establishing smart nanomedical vehicles with theragnostic applications [1,2,3,4,5]. Polymers are extensively used to this end, due to their great versatility and biocompatibility, and their ability to encapsulate, adsorb and covalently bind drugs and penetrate through biological barriers and reach the target site effectively [6,7]. These polymeric nanocarriers can be further modified as stimuli-responsive systems based on triggered release mechanisms (pH, ionic strength, electric field, temperature, light, etc.) to achieve maximal therapeutic efficacy [8]. They can be prepared from available, low-cost resources and can be manipulated to meet markers for bioimaging and sensing devices and have recently been used to develop mul‐

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