Main preparation methods of new fluorescent nanomaterial carbon quantum dots and their applications in tumor diagnosis and treatment

Abstract

BACKGROUND: Carbon quantum dots are a novel fluorescent nanomaterial that, thanks to their excellent optical properties, good biocompatibility, and low toxicity, show significant potential in the field of tumor diagnosis and treatment. OBJECTIVE: To systematically review the methods used to prepare carbon quantum dots and their applications in tumor diagnosis and treatment. METHODS: Relevant literature was retrieved from the China National Knowledge Infrastructure (CNKI) and PubMed databases using computer searches. Chinese search terms were “tumor therapy, carbon quantum dots, arc discharge, electrochemical discharge, drug delivery, fluorescence imaging.” English search terms were “CQD tumor therapy, carbon quantum dot preparation, carbon quantum dots, tumor diagnosis and treatment.” According to the inclusion and exclusion criteria, 102 articles were finally included in the review. RESULTS AND CONCLUSION: Common preparation methods for carbon quantum dots are top-down method and bottom-up method. In terms of preparation, the top-down method (arc discharge, electrochemical, laser ablation) uses graphite and other carbon materials as precursors, which is simple to operate but produces many by-products and has low quantum yield; after purification, the yield can be improved. The bottom-up method (hydrothermal, microwave, and template) utilizes biomass or small-molecule carbon sources, offering environmental friendliness and excellent water solubility of the products. In tumor diagnosis and therapy, carbon quantum dots exert their effects through multiple synergistic mechanisms. Fluorescence imaging enables early diagnosis and real-time monitoring by labeling tumor cells; photothermal therapy converts light energy into heat to kill tumor cells; photodynamic therapy generates reactive oxygen species to damage tumor cell biomolecules; as drug carriers, carbon quantum dots can target delivery of antitumor drugs to tumor sites, reducing adverse effects; in immunotherapy, they trigger immunogenic cell death, reverse the immunosuppressive microenvironment, and activate the stimulator of interferon genes pathway, converting “cold” tumors to “hot” tumors; in multimodal therapy, carbon quantum dots integrate chemotherapy, phototherapy, and immunotherapy to achieve high tumor inhibition rates.

1. Introduction

Tumors are diseases caused by abnormal proliferation of local tissue cells that have lost normal growth regulation at the genetic level. Despite significant progress in molecular mechanisms of tumor therapy, tumors remain a major threat to human health [1-2]. The treatment modalities vary depending on tumor type, location, nature, and stage; currently, the most effective approaches are surgical resection, radiotherapy, and chemotherapy [3]. Surgical resection is the preferred option for early-stage tumors, but it has time constraints; radiotherapy and chemotherapy, while inhibiting tumor cell division and controlling growth, lack targeting, often damaging normal cells and causing severe side effects [4-5]. Therefore, developing novel nanomaterials that specifically recognize and eliminate tumor cells while minimizing damage to normal tissues is crucial.

Carbon is the most abundant element in nature and has developed rapidly in the field of nanomaterials due to its high stability and wide availability [6]. Among various carbon-based nanomaterials, carbon quantum dots (CQDs) have attracted extensive attention in medicine because of their unique properties [7]. CQDs are near-spherical carbon nanoparticles with sizes less than 10 nm, and their surfaces can be modified with hydrophilic functional groups to achieve excellent water solubility and biocompatibility [8]. CQDs also exhibit excellent fluorescence properties, offering broad application prospects in fluorescence imaging and sensors [9-10]. Moreover, due to the special tumor microenvironment, tumor tissues have enhanced permeability, promoting the accumulation of CQDs, a property known as the enhanced permeability and retention (EPR) effect [11-12]. The EPR effect enhances the tumor targeting of CQDs, and if applied clinically, it is expected to significantly reduce adverse effects of tumor therapy [13]. Compared with traditional heavy metal quantum dots, the toxicity of CQDs is significantly lower [14], further broadening their application prospects in biomedicine.

This review aims to summarize the optimization strategies for CQD preparation (e.g., purification to enhance quantum yield) and their application progress in tumor fluorescence imaging, photothermal/photodynamic therapy, targeted drug delivery, immunomodulation, and multimodal synergistic therapy, with the goal of providing a theoretical basis for developing efficient and low-toxicity tumor theranostic nanoplatforms.