Innovative tumor interstitial fluid-triggered carbon dot-docetaxel nanoassemblies for targeted drug delivery and imaging of HER2-positive breast cancer

Dan Xu; Dongnan Guo; Jing Zhang; Xueping Tan; Zijie Deng; Xiaofang Hou; Sicen Wang

doi:10.1016/j.ijpharm.2024.124145

Innovative tumor interstitial fluid-triggered carbon dot-docetaxel nanoassemblies for targeted drug delivery and imaging of HER2-positive breast cancer

Int J Pharm. 2024 Apr 26:124145. doi: 10.1016/j.ijpharm.2024.124145. Online ahead of print.

Authors

Dan Xu¹, Dongnan Guo¹, Jing Zhang¹, Xueping Tan¹, Zijie Deng¹, Xiaofang Hou², Sicen Wang³

Affiliations

¹ School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China; Shaanxi Engineering Research Center of Cardiovascular Drugs Screening & Analysis, Xi'an 710061, China.
² School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China; Shaanxi Engineering Research Center of Cardiovascular Drugs Screening & Analysis, Xi'an 710061, China. Electronic address: houxiaofang@mail.xjtu.edu.cn.
³ School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China; Shaanxi Engineering Research Center of Cardiovascular Drugs Screening & Analysis, Xi'an 710061, China. Electronic address: wangsc@mail.xjtu.edu.cn.

PMID: 38679242
DOI: 10.1016/j.ijpharm.2024.124145

Abstract

In this study, we have developed an innovative pH-triggered nanomedicine delivery system, targeting HER2-positive breast cancer cells for effective low-cost, imaging-guided drug delivery and precise therapy. The key feature of this system lies in its unique tumor interstitial fluid microenvironment-responsive drug release behavior which achieved tumor site-specific drug delivery. Our in vitro experiments demonstrated that the carbon dot-integrated material achieves more efficient DTX release (96.13 % at 72 h) in the tumor interstitial fluid microenvironment (pH 6.5), thereby boosting drug concentration at the tumor site and enhancing therapeutic efficacy. Further cell experiments confirmed the system's significant inhibitory effect on HER2-positive tumor cells SKBR3 in a pH 6.5 environment, and apoptosis assays indicating a notable increase in early cell apoptosis (from 8.39 % to 24.61 % compared with pH 7.4). Furthermore, the integration of HER2 aptamer within the carbon dot-based system enables targeted recognition and binding to tumor cells, ensuring more precise delivery of DTX while minimizing potential side effects. Crucially, the carbon dots in this system emit superior red fluorescence (the QY = 47.64 % excited at 535 nm compared with Rodamine 6G), enabling real-time visualization of the drug delivery process. This feature provides valuable feedback on treatment effectiveness, facilitating necessary adjustments. The small size (1.88 ± 0.48 nm) of carbon dots significantly improved their ability to penetrate biological barriers, while their low toxicity (no significant cell toxicity under 350 μg/mL) contributed to the formulation's outstanding biocompatibility. Overall, this carbon dot-enhanced drug delivery system offers immense potential for enhancing drug efficacy, minimizing side effects, and providing real-time treatment monitoring, thus proposing a innovate strategy for breast cancer therapy.

Keywords: Carbon dots; Cell imaging; HER2 targeting; pH-triggered drug release.