Development of Multifunctional Biopolymeric Auto-Fluorescent Micro- and Nanogels as a Platform for Biomedical Applications.

Arti Vashist,Ajeet Kaushik,Madhavan Nair,Venkata Atluri,Marisela Agudelo,Jessica C Ramella-Roman,Zaohua Huang,Andrea Raymond,Hitendra S Chand,Atul Vashist,Ilyas Saytashev,Tiyash Parira,Roozbeh Nikkhah-Moshaie,Asahi Tomitaka,Andriy Durygin

doi:10.3389/fbioe.2020.00315

Abstract

The emerging field of theranostics for advanced healthcare has raised the demand for effective and safe delivery systems consisting of therapeutics and diagnostics agents in a single monarchy. This requires the development of multi-functional bio-polymeric systems for efficient image-guided therapeutics. This study reports the development of size-controlled (micro-to-nano) auto-fluorescent biopolymeric hydrogel particles of chitosan and hydroxyethyl cellulose (HEC) synthesized using water-in-oil emulsion polymerization technique. Sustainable resource linseed oil-based polyol is introduced as an element of hydrophobicity with an aim to facilitate their ability to traverse the blood-brain barrier (BBB). These nanogels are demonstrated to have salient features such as biocompatibility, stability, high cellular uptake by a variety of host cells, and ability to transmigrate across an in vitro BBB model. Interestingly, these unique nanogel particles exhibited auto-fluorescence at a wide range of wavelengths 450–780 nm on excitation at 405 nm whereas excitation at 710 nm gives emission at 810 nm. In conclusion, this study proposes the developed bio-polymeric fluorescent micro- and nano- gels as a potential theranostic tool for central nervous system (CNS) drug delivery and image-guided therapy.

Highlights

Numerous systems have been developed as theranostics agents, which included multi-functional inorganic nanoparticles (Degli Esposti et al, 2018), quantum dots (Ho and Leong, 2010), and many radiolabeled biomarkers (Kang et al, 2018), the clinical applications of these agents have provoked practical challenges
Biopolymers chitosan having medium molecular weights (190– 310 kDa) and hydroxyethyl cellulose (HEC) have been used for the development of hydrogel particles
It was hypothesized that the hydrophobic modification will restrict the swelling capacity of the polymeric hydrogel particles, which thereby will enhance their hydrophobicity and help them traverse through the blood-brain barrier (BBB)

Summary

Introduction

Numerous systems have been developed as theranostics agents, which included multi-functional inorganic nanoparticles (Degli Esposti et al, 2018), quantum dots (Ho and Leong, 2010), and many radiolabeled biomarkers (Kang et al, 2018), the clinical applications of these agents have provoked practical challenges. The current strategy of developing bio-polymeric theranostic agents has pronounced conviction of incorporating inherent features of no toxicity, biodegradability, biocompatibility and high sensitivity In this regard, fluorescent hydrogels have attracted great attention of us and others due to their smart biomaterials like features and have been intensively explored as most convenient tracers and therapeutics for decades. The entrapment of fluorophores in the hydrogel matrix is tedious and limiting process as the tagging or entrapping fluorescent dyes or compounds and their photobleaching may affect their characteristic features like biocompatibility and biodegradability (Zhang and Yang, 2013) Such DDS has exhibited performance in a personalized manner due to tunable salient features including size, morphology, targeted delivery, and release profile (Allen and Cullis, 2004)

Objectives

Methods

Results

Discussion

Conclusion