Near-infrared carbon dots: pioneering emerging frontiers in biomedical applications

Abstract

Carbon dots (CDs) are fluorescent carbon-based nanomaterials with sizes smaller than 10 nm, that are renowned for their exceptional properties, including superior anti-photobleaching, excellent biocompatibility, and minimal toxicity, which have received significant interest. Near-infrared (NIR) light has emerged as an ideal light source in the biological field due to its advantages of minimal scattering and absorption, long wavelength emission, increased tissue penetration, and reduced interference from biological backgrounds. CDs with efficient absorption and/or emission characteristics in the NIR spectrum have shown remarkable promise in biomedical uses. This study provides a comprehensive overview of the preparation methods and wavelength modulation strategies for near-infrared CDs and reviews research progress in their use in the areas of biosensing, bioimaging, and therapy. It also discusses current challenges and clinical prospects, aimed at deepening our understanding of the subject and promoting further advances in this field.

1. Introduction

Near-infrared (NIR, including the first NIR window 700–900 nm and the second window 1000–1700 nm) is regarded as an advanced diagnostic and therapeutic modality in nanomedicine, bioimaging, photothermal therapy and other fields due to its advantages of high resolution and deep tissue penetration[1–3]. Although commercial dipyrromethene boron difluoride (BODIPY) and Alexa dyes have near-infrared emission, their applicability is limited due to their high cost and complex synthesis[4]. Organic dyes are susceptible to photobleaching[5], and suffer from severe quenching effects caused by aggregation[6], which limits their potential for observing structural changes in live cell. To overcome these limitations, various nanomaterials based on silicon dioxide[7], rare earth materials[8], quantum dots[9], metals and semiconductors[10–11] have been developed. These nanomaterials exhibit superior photostability compared to organic fluorophores. However, despite their advantages, the clinical translation of these nanomaterials faces challenges. One major challenge is the requirement for targeted ligands, which can complicate the synthesis process and lead to nonspecific interactions. Moreover, the complex synthesis routes associated with these nanomaterials can hinder their scalability and practical application. Additionally, high cytotoxicity observed in vitro limits their suitability for clinical use[12].

As a novel carbon-based nanomaterial, carbon dots (CDs) have unique photophysical properties and good biocompatibility, thus exhibiting attractive application prospects in the field of biomedicine[13–15]. CDs are a type of zero-dimensional (0D) carbon nanomaterials characterized by their sp2/sp3 carbon frameworks and the presence of surface functional groups or polymer chains. In general, the synthesis of CDs can be achieved through either top-down or bottom-up approaches. Top-down methods primarily involve the exfoliation of macroscopic materials to produce nano-sized carbon particles. This can be achieved through chemical oxidation, laser ablation, hydrothermal or electrochemical methods[16]. Since the precursor materials used in these top-down methods are typically crystalline, the resulting CDs exhibit mainly sp2 hybridization[17]. On the other hand, bottom-up preparation methods are used to scale up the production of CDs. These methods include traditional pyrolysis, microwave-assisted methods, hydrothermal/solvothermal methods, magneto-thermal methods, microfluidic methods, and ultrasound methods[18–20]. The influencing factors on the fluorescent properties of CDs mainly include quantum confinement effect, edge structure effect, atomic doping effect, surface functional group effect, molecular state effect and environmental effect[21–23]. CDs offer distinct advantages compared to other nanomaterials. Firstly, they exhibit