HER2-positive breast cancer, defined by the amplification or overexpression of HER2/neu, a key receptor tyrosine kinase in the epidermal growth factor receptor family (Adrienne and Eric, 2019, Iqbal and Iqbal, 2014). This subtype represents approximately 20 % of breast cancer cases (Adrienne and Eric, 2019, Larissa et al., 2021) and is associated with poor prognosis in the absence of systemic therapy. Current clinical therapies for HER2-positive breast cancer include anti-ERBB2 antibodies (trastuzumab and pertuzumab) and small-molecule tyrosine kinase inhibitors (lapatinib and neratinib) (Fan et al., 2014). While these drugs are effective, they frequently come with high costs and severe side effects, including damage to healthy tissues. To address these issues, several HER2-targeting aptamers have been synthesized as a low-cost, stable, and specific alternative. Aptamers such as HApt, Apt, and HB5 have shown promising prospects in targeting drug delivery (Chowdhury et al., 2020, Ghassami et al., 2019, Heo et al., 2018, Jiang et al., 2017, Niazi et al., 2015, Nguyen et al., 2017, Powell et al., 2017, Wu et al., 2020). As a result, various drug-loaded nanoparticles have been developed and modified with HER2 aptamers (Nguyen et al., 2017, Powell et al., 2017), leveraging their specific recognition and binding capabilities to enable targeted chemotherapy delivery to tumor sites.

To enhance drug delivery efficiency, various trigger-release drug carrier systems, including temperature, ultrasoud or pH-triggering, have been developed (Kanamala et al., 2016, Zhu and Chen, 2015). Traditionally targeting the acidic tumor microenvironment, these systems typically focus on pH levels such as 5.0 or 5.5 (Chen et al., 2017, Mewada et al., 2014), contrasting with the normal tissue pH of 7.4. However, recent research reveals a more refined pH gradient within tumors. Specifically, intracellular tumor environments and lysosomes have a pH around 5.5, while tumor interstitial fluid and nearby solid tumor areas are about pH 6.5 (Alvarez-Lorenzo and Concheiro, 2014, Kong et al., 2018, Pan et al., 2019, Wang et al., 2017). This distinct pH levels are crucial for developing more precise, pH-responsive drug carriers, enabling targeted and efficient drug release at specific tumor sites.

Carbon dots (CDs) have become recognized as a significant carbon-based material, known for their applications in imaging (Liu et al., 2019) and drug delivery due to their favorable optical properties, high drug loading capacity, easy surface functionalization, good biocompatibility, and low toxicity (Liu et al., 2020a, Liu et al., 2020b, Panwar et al., 2019). The characteristics of CDs have enabled their use in imaging-guided chemotherapy drugs delivery (Bao et al., 2019, Chang et al., 2019, Deng et al., 2018, Jin et al., 2019, Liu et al., 2020a, Liu et al., 2020b, Lu et al., 2019, Sun et al., 2020, Sun et al., 2019, Tang et al., 2013) and phototherapy (Shu et al., 2021, Sun et al., 2019, Williams et al., 1983) for the treatment of cancers. The use of CDs in imaging-guided drug delivery systems allows therapists to monitor the absorption, distribution, metabolism, and excretion of drugs in real-time, providing greater insight into the treatment process and improving the safety of medication. With this technology, therapists can optimize drug dosages and delivery routes for maximum effectiveness and minimal side effects.

In this study, we developed a nanomedicine delivery system HPRCD@DTX, aimed specifically at tumor extracellular microenvironment of HER2-positive breast cancer. The system comprises a HER2 aptamer, polyethylene glycol (PEG), red carbon dots (RCDs), and docetaxel (DTX). A key feature of HPRCD@DTX is its pH-triggered drug release, particularly effective in the tumor interstitial fluid (pH 6.5) and tumor endochylema (pH 5.5) microenvironments. This characteristic guarantees enhanced drug release at the tumor site, thereby increasing its concentration and amplifying its therapeutic effect. Furthermore, the red carbon dots in this system offer distinct red fluorescence, facilitating real-time monitoring of the drug delivery process. This imaging feature is essential in directing the treatment of HER2-positive breast cancer. Lastly, the HER2 aptamer facilitates targeted delivery to cancer cells through specific binding to HER2 receptors, thereby boosting treatment efficacy and minimizing side effects. Collectively, HPRCD@DTX represents a promising approach for precise, imaging-guided cancer therapy, integrating efficient drug delivery with real-time monitoring of treatment.