Abstract

Theranostic systems have attracted considerable attention for their multifunctional approach to cancer. Among these, carbon nanodots (CDs) emerged as luminescent nanomaterials due to their exceptional chemical properties, synthetic ease, biocompatibility, and for their photothermal and fluorescent properties useful in cancer photothermal therapy. However, premature renal excretion due to the small size of these particles limits their biomedical application. To overcome these limitations, here, hybrid poly(lactic-co-glycolic acid) (PLGA-CDs) nanoparticles with suitable size distribution and stability have been developed. CDs were decisive in the preparation of polymeric nanoparticles, not only conferring them photothermal and fluorescent properties, needed in theranostics, but also having a strategic role in the stabilization of the system in aqueous media. In fact, CDs provide stable PLGA-based nanoparticles in aqueous media and sufficient cryoprotection in combination with 1% PVP. While PLGA nanoparticles required at least 5% of sucrose. Comparing nanosystems with different CDs content, it is also evident how these positively impinge on the loading and release of the drug, favoring high drug loading (~4.5%) and a sustained drug release over 48 h. The therapeutic and imaging potentials were finally confirmed through in vitro studies on a breast cancer cell line (MDA-MB-231) using fluorescence imaging and the MTS cell viability assay.

Highlights

  • In the era of precision medicine, theranostic nanomaterials represent a new valid approach to drug development through a strategic combination of tumor diagnosis, monitoring and therapy in a single targeted nanoplatform, resulting in overcoming severe limitations of conventional chemotherapy which often lead to the failure of treatment and the development of multidrug resistance (MDR) [1,2]

  • We demonstrated that the presence of carbon nanodots (CDs) inside the biodegradable PLGA nanomatrix impinge on several formulation parameters determining the stability in physiological fluids, drug loading processes and drug release profiles

  • PLGA allowed an increase in size, reducing premature renal excretion of CDs, the encapsulation of CDs proved capable of effectively stabilizing the system, increasing drug loading capacity and prolonging the release over time

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Summary

Introduction

In the era of precision medicine, theranostic nanomaterials represent a new valid approach to drug development through a strategic combination of tumor diagnosis, monitoring and therapy in a single targeted nanoplatform, resulting in overcoming severe limitations of conventional chemotherapy which often lead to the failure of treatment and the development of multidrug resistance (MDR) [1,2]. One advanced application of theranostic nanomaterials is imaging-guided photothermal therapy (IG-PTT), a promising strategy which combines the use of near-infrared (NIR) laser photoabsorbers with contrast agent properties. While the image guidance provides a precisely localization of the tumor region, the biodistribution of the nanosystems and the monitoring of the treatment, the conversion of NIR light energy into heat over the physiological temperature range (41–45 ◦C) by photothermal agents induces selective thermal ablation of cancer cells and their hypersensitization towards xenobiotics [3,4,5]. Various nanomaterials with low toxicity, strong fluorescence and photothermal conversions property within the biological transparency window (620–1100 nm) have been proposed for IG-PTT application such as organic dyes, noble metal nanoparticles and carbon derivates. Despite the higher thermo/photostability of noble metal nanoparticles (e.g., gold nanoparticles) against organic dyes, they are characterized by a low renal excretion with possible organ deposits and potential long-term toxicity which limit their clinical application [7,8,9]

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