Fluorescent Nanodiamonds Based Theranostic Platform for pH‐Sensitive Drug Delivery and Quantum Sensing
At a Glance
Section titled “At a Glance”| Metadata | Details |
|---|---|
| Publication Date | 2025-10-09 |
| Journal | Advanced Functional Materials |
| Authors | Kaiqi Wu, Siyu Fan, Yue Zhang, Willem Woudstra, Th. Mulder |
| Institutions | University Medical Center Groningen, University of Groningen |
| Analysis | Full AI Review Included |
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Executive Summary
Section titled “Executive Summary”- Developed a pH-sensitive nanodiamond (ND) platform (FND-HPG-DMA-DZX) for targeted drug delivery and redox monitoring in triple-negative breast cancer (TNBC) cells.
- The platform combines pH-sensitive drug release of Diazoxide (DZX) with quantum sensing capabilities via nitrogen-vacancy (NV) centers in the nanodiamonds.
- Demonstrated controlled drug release in mildly acidic conditions (pH 6.5), mimicking the tumor microenvironment.
- Showed that DZX release leads to increased mitochondrial ROS (O2-) levels and a decrease in radical load in endo/lysosomal regions.
- Utilized diamond relaxometry to monitor intracellular redox dynamics at the location of drug release.
- The multifunctional nanoplatform offers potential for advancing targeted cancer therapy and redox biology research.
- Provides novel insights into DZX’s mechanism of action, particularly its role in modulating mitochondrial ROS and cellular redox balance.
Technical Specifications
Section titled “Technical Specifications”| Parameter | Value | Unit | Context
| DZX concentration (µg/mL) | 10 |
| DZX concentration (µM) | 2.75 |
| ND size (unmodified) | 0-150 | nm |
| FND size (fluorescent) | 70 | nm |
| NV center concentration in FND | 3 | ppm |
| HPG Polymerization Time (this study) | 4 | h |
| HPG Polymerization Temperature | 140 | °C |
| DZX Release at pH 6.5 (8h) | ≈78 | % |
| DZX Release at pH 7.4 (8h) | ≈26 | % |
| IC50 of DZX | 1.34 | µM |
| Laser Power (Relaxometry) | 50 | µW |
| Excitation Wavelength (Relaxometry) | 532 | nm |
| Dark Interval Range (Relaxometry) | 0.2 - 1000 | µs |
| T1 (FND-HPG-DMA-DZX, 4h) | 154 | µs |
| T1 (FND-HPG-DMA-DZX, 24h) | 194 | µs |
| Lysoview 405 Blue Concentration | 1 | µg/mL |
| MitoSOX Green Concentration | 1 | µM |
Key Methodologies
Section titled “Key Methodologies”- ND-HPG Synthesis:
- ND powder dispersed in glycidol via sonication.
- Stirred at 140 °C for 4 h under N2 atmosphere.
- Methanol added during cooling to prevent gel formation.
- Centrifuged, washed with methanol, and dried.
- ND-HPG-DMA Synthesis:
- DMA dissolved in dichloromethane and mixed with oxalyl chloride/DMF.
- Stirred on ice, then at room temperature.
- Vacuum dried, dissolved in DCM.
- ND-HPG suspended in DCM via sonication under Ar.
- Mixed CDM and ND-HPG solutions, stirred overnight.
- Collected by centrifugation, washed with DCM, and dried.
- ND-HPG-DMA-Cargo (DZX) Synthesis:
- ND-HPG-DMA suspended in anhydrous DMSO via sonication under Ar.
- Amino group-containing molecules (DZX) added.
- pH-Responsive Release Profile:
- ND-HPG-DMA-Alexa 488 added to petri dish.
- Unattached complex removed.
- pH 7.4 and pH 6.5 PBS buffer added.
- Incubated for 4 h, imaged using fluorescence microscopy.
- Cellular Uptake and Subcellular Location:
- MDA-MB-231 cells incubated with FND/FND-HPG-DMA-DZX.
- Washed, fixed with paraformaldehyde, permeabilized with Triton X-100.
- Nuclei labeled with DAPI, actin cytoskeleton visualized with phalloidin-FITC.
- Imaged using confocal microscopy.
- Intracellular Diamond Relaxometry:
- FND-HPG-DMA-DZX internalized by MDA-MB-231 cells.
- Optically polarized using a 532 nm laser pulse (5 µs).
- Variable dark interval (0.2-1000 µs).
- NV fluorescence read out, photons collected via photodetector.
- Photon counts plotted as a function of dark interval to extract T1.
Commercial Applications
Section titled “Commercial Applications”- Quantum Sensing: Development of advanced sensors for intracellular environments, redox biology, and cancer diagnostics.
- Targeted Drug Delivery: Development of pH-sensitive drug delivery systems for cancer therapy.
- Nanomaterials: Synthesis and functionalization of nanodiamonds for biomedical applications.
- Pharmaceuticals: Targeted delivery of therapeutics to specific cellular compartments.
View Original Abstract
Abstract Breast cancer is the most common cancer in women worldwide. Triple negative breast cancer (TNBC) is particularly problematic due to the poor prognosis and limited treatment options. Here, nanodiamond particles are synthesized for delivering the cancer drug Diazoxide (DZX) to TNBC cells. The multifunctional nanodiamond (ND) platform integrates pH‐sensitive drug release and advanced quantum sensing capabilities, enabling precise drug delivery and monitoring of intracellular redox dynamics. Due to the nitrogen‐vacancy (NV) centers in the diamond particles, they can be imaged. Further, quantum sensing is demonstrated specifically at the location where the drug is released. After 24 h of treatment at 10 µg mL −1 diamond‐DZX complex (equivalent to 2.75 µM DZX), diamond relaxometry reveals a decreased radical load in the endo/lysosomal regions, while MitoSOX fluorescence indicates elevated mitochondrial ROS (O 2 − ) levels, suggesting the activation of intracellular redox homeostasis. By combining controlled drug delivery with advanced quantum sensing, this work provides novel insights into DZX’s mechanism of action, particularly its role in modulating mitochondrial ROS and cellular redox balance. This multifunctional nanoplatform demonstrates significant potential for advancing targeted cancer therapy and redox biology research.