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 of Groningen, University Medical Center Groningen |
| Analysis | Full AI Review Included |
Technical Documentation & Analysis: Fluorescent Nanodiamonds for Theranostics
Section titled “Technical Documentation & Analysis: Fluorescent Nanodiamonds for Theranostics”This document analyzes the research article “Fluorescent Nanodiamonds Based Theranostic Platform for pH-Sensitive Drug Delivery and Quantum Sensing” to highlight the critical role of high-quality CVD diamond materials and connect the study’s requirements directly to 6CCVD’s advanced manufacturing capabilities.
Executive Summary
Section titled “Executive Summary”This research successfully demonstrates a multifunctional nanodiamond (ND) platform for targeted cancer therapy and in situ redox monitoring, leveraging the unique properties of Nitrogen-Vacancy (NV) centers.
- Theranostic Platform: A pH-sensitive nanoplatform (FND-HPG-DMA-DZX) was synthesized using Fluorescent Nanodiamonds (FNDs) to deliver Diazoxide (DZX) specifically to Triple Negative Breast Cancer (TNBC) cells.
- Targeted Release: The platform utilizes a pH-labile amide-oxobutenoic acid linkage, enabling controlled release of DZX (≈78% release efficiency) in the mildly acidic endo/lysosomal environment (pH 6.5).
- Quantum Sensing: NV-center diamond quantum relaxometry (T₁ measurement) was employed in situ to monitor intracellular free radical load and redox dynamics at the subcellular level.
- Redox Homeostasis Insight: The study confirmed that DZX induces mitochondrial Reactive Oxygen Species (mitoROS) production, while T₁ relaxometry simultaneously showed a significant decrease in free radical load in the cytoplasm/lysosomes, indicating the activation of redox homeostasis pathways.
- Material Requirement: The success hinges on high-quality FNDs with controlled NV center concentration (3 ppm) and robust surface functionalization (HPG, DMA linker).
- Core Value: This work validates the use of diamond quantum sensing for real-time, compartment-specific monitoring of drug mechanisms, opening new avenues for targeted cancer research.
Technical Specifications
Section titled “Technical Specifications”The following hard data points were extracted from the research paper, detailing the material properties and performance metrics of the FND-HPG-DMA-DZX complex.
| Parameter | Value | Unit | Context |
|---|---|---|---|
| Nanodiamond Core Size | 70 | nm | Fluorescent Nanodiamond (FND) |
| NV Center Concentration | 3 | ppm | Optimized for quantum sensing/relaxometry |
| DZX Loading (wt%) | 5.9 | wt% | Final ND-HPG-DMA-DZX complex composition |
| HPG Loading (wt%) | 10.4 | wt% | Hyperbranched Polyglycerol shell |
| DMA Loading (wt%) | 7.3 | wt% | pH-sensitive linker |
| Drug Release Trigger pH | 6.5 | pH | Mimics acidic tumor microenvironment/lysosomes |
| DZX Release Efficiency (pH 6.5) | ≈78 | % | Cumulative release over 8 hours |
| DZX Concentration (Cell Study) | 10 µg mL⁻¹ (2.75 µM) | Concentration | Used for cellular uptake and sensing |
| Hydrodynamic Diameter (ND) | 122 ± 4 | nm | Pristine Nanodiamonds in H₂O |
| Hydrodynamic Diameter (Final Complex) | 225 ± 32 | nm | ND-HPG-DMA-DZX after conjugation |
| Zeta-Potential (Final Complex) | -26 ± 4 | mV | After DZX conjugation (contributes to uptake) |
| T₁ Relaxation Time (Peak) | 194 | µs | Observed at 24 h incubation (indicates decreased radical load) |
| Laser Power (Relaxometry) | 50 | µW | Measured at objective back aperture |
Key Methodologies
Section titled “Key Methodologies”The experimental success relied on precise, multi-step chemical functionalization of the nanodiamond surface and the application of advanced quantum sensing techniques.
- Nanodiamond Core Preparation: Fluorescent Nanodiamonds (FNDs, 70 nm, 3 ppm NV) were selected as the core material, providing both imaging (fluorescence) and sensing (NV centers) capabilities.
- HPG Grafting (ND-HPG): Hyperbranched polyglycerol (HPG) was grafted onto the ND surface via ring-opening polymerization of glycidol at 140 °C for 4 hours under N₂ atmosphere to enhance colloidal stability.
- DMA Linker Attachment (ND-HPG-DMA): The pH-sensitive linker, 3-(4-methyl-2,5-dioxo-2,5-dihydrofuran-3-yl) propanoic acid (DMA), was attached through esterification activated by oxalyl chloride.
- DZX Conjugation: Diazoxide (DZX) was conjugated to the ND-HPG-DMA complex via a ring-opening reaction between the DZX amine group and the DMA cyclic anhydride, forming the pH-labile amide-oxobutenoic acid linkage.
- Intracellular Localization: Confocal microscopy and Lysotracker staining were used to confirm that the FND-HPG-DMA-DZX particles predominantly localized within endo/lysosomal compartments.
- Diamond Quantum Relaxometry (T₁): A custom-built magnetometry setup was used to measure the T₁ relaxation time of the NV centers. The protocol involved optical polarization (532 nm laser, 5 µs pulse) followed by a variable dark interval (0.2 to 1000 µs) to monitor local free radical concentrations in situ.
6CCVD Solutions & Capabilities
Section titled “6CCVD Solutions & Capabilities”The research highlights the critical need for high-specification diamond materials with precise NV center control and robust surface chemistry—core competencies of 6CCVD. While this study utilized nanodiamonds, 6CCVD provides the foundational, high-purity Single Crystal Diamond (SCD) and Polycrystalline Diamond (PCD) required for both bulk quantum sensing and the creation of custom nanodiamond precursors.
Applicable Materials for Quantum Sensing & Theranostics
Section titled “Applicable Materials for Quantum Sensing & Theranostics”| Application Requirement | 6CCVD Material Recommendation | Specification Match |
|---|---|---|
| High-Purity NV Precursors | Optical Grade Single Crystal Diamond (SCD) | Ideal precursor material for creating highly uniform FNDs via subsequent irradiation and annealing. Ensures minimal defects and high NV yield. |
| Integrated Quantum Sensors | SCD Plates (Custom Thickness/Doping) | For scaling the quantum sensing platform into integrated devices (e.g., microfluidic chips), we offer SCD up to 500 µm thick with precise, controlled nitrogen doping (e.g., 3 ppm) during the MPCVD growth process. |
| Electrochemical Sensing | Heavy Boron-Doped Diamond (BDD) | If the research extends to electrochemical redox sensing, our BDD wafers provide superior chemical inertness and wide potential windows. |
| Large-Area Substrates | Polycrystalline Diamond (PCD) Wafers | Available up to 125 mm diameter for large-scale sensor integration or high-throughput screening platforms. |
Customization Potential
Section titled “Customization Potential”The complexity of the FND-HPG-DMA-DZX platform requires advanced material engineering, which 6CCVD is uniquely positioned to support:
- Custom Dimensions: While the paper used 70 nm particles, 6CCVD can supply SCD plates up to 125 mm in diameter and thicknesses ranging from 0.1 µm to 500 µm (wafers) or up to 10 mm (substrates) for bulk sensing or integrated device fabrication.
- Precise NV Engineering: We offer custom nitrogen incorporation during CVD growth to achieve specific NV concentrations (e.g., the 3 ppm used here) necessary to optimize T₁ relaxometry sensitivity for various biological environments.
- Surface Preparation: We provide ultra-smooth polishing (Ra < 1 nm for SCD, < 5 nm for inch-size PCD) and custom surface terminations (e.g., oxygen, hydrogen) essential for subsequent complex chemical functionalization steps like HPG/DMA grafting.
- Metalization Services: For integrating diamond sensors into microelectronic or microfluidic systems, 6CCVD offers internal metalization capabilities, including Au, Pt, Pd, Ti, W, and Cu deposition.
Engineering Support
Section titled “Engineering Support”6CCVD’s in-house team of PhD material scientists specializes in optimizing CVD diamond growth parameters for quantum applications. We can assist researchers in selecting the optimal diamond grade (SCD vs. PCD), doping level, and surface preparation necessary to replicate or extend this theranostic/redox sensing project into integrated device formats.
For custom specifications or material consultation, visit 6ccvd.com or contact our engineering team directly.
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.