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Liu, Zongjun, et al. Colloids and Surfaces A: Physicochemical and Engineering Aspects 568 (2019): 436-444.
Mesoporous silica coated upconversion nanoparticles (UCNP@mSiO₂) have been effectively utilized in the design of light-responsive nanovalves for controlled drug delivery and real-time monitoring. In this study, a novel nanovalve system was developed by modifying the UCNP@mSiO₂ surface with photo-cleavable pyrenemethyl ester (Py), which associates with β-cyclodextrin (β-CD) gatekeepers to block the mesopores and entrap drugs.
Upon near-infrared (NIR) light irradiation, UCNPs convert NIR to ultraviolet (UV) and visible (Vis) emissions. The upconverted UV light cleaves the Py linkage, detaching β-CD and triggering precise drug release. To enable simultaneous drug release monitoring, β-CD was conjugated with fluorescein isothiocyanate (FITC). Prior to release, luminescence resonance energy transfer (LRET) between UCNP and Py/FITC-β-CD quenches UCNP's visible emission. After detachment, LRET is disrupted, restoring UCNP luminescence-thus enabling quantitative tracking of drug release.
This nanovalve system shows negligible premature release, high responsiveness to varying NIR power densities, and excellent in vitro anticancer activity against HeLa cells. The dual function of controlled release and self-reporting highlights the potential of UCNP@mSiO₂ nanoplatforms in intelligent drug delivery applications.
These findings offer valuable insights into the development of multifunctional, NIR-responsive drug carriers with built-in release monitoring capabilities for advanced biomedical applications.
Xu, Fang, et al. Materials Letters 167 (2016): 205-208.
Mesoporous-silica-coated upconversion nanoparticles (UCNPs), specifically NaYF₄:Yb/Er@SiO₂, have emerged as promising nanoplatforms for near-infrared (NIR)-activated photodynamic therapy (PDT) due to their deep tissue penetration and minimal photodamage to healthy cells. In this study, a high-surface-area (770 m²/g) nanocomposite with ~2 nm mesopores was successfully synthesized and loaded with Vitamin B12 (VB12), a biocompatible and clinically approved compound, as the photosensitizer.
Upon NIR irradiation, the UCNPs convert 980 nm light to visible emissions at ~545 nm, which matches the absorption maximum of VB12. This spectral overlap enables efficient excitation of VB12, which subsequently transfers energy to ground-state molecular oxygen, producing cytotoxic reactive oxygen species (ROS). These ROS mediate oxidative damage to cancer cells, enabling effective PDT.
Compared to conventional photosensitizers, VB12 offers advantages in safety, availability, and biological compatibility. Additionally, the mesoporous silica coating ensures high drug-loading capacity and efficient interaction between the UCNP emission and surface-bound photosensitizers. In vitro studies confirmed enhanced phototoxicity against cancer cells upon NIR activation.
This study illustrates the clinical potential of mesoporous-silica-coated upconversion nanoparticles as multifunctional carriers for non-invasive, deep-tissue PDT. The biocompatibility of VB12, combined with the precision and responsiveness of UCNPs, makes this nanoplatform a compelling candidate for future oncological applications.
Lai, Jinping, et al. ACS nano 9.5 (2015): 5234-5245.
Mesoporous-silica-coated multicolor upconversion nanoparticles (UCNP@MSN) have been innovatively engineered as ATP-responsive drug delivery systems (DDS) with integrated real-time monitoring capabilities. In this system, NaYF₄:Yb/Er UCNPs with multiple emission peaks across the UV-NIR range are encapsulated with mesoporous silica and surface-functionalized with zinc-dipicolylamine analogs (TDPA-Zn²⁺). These exterior metal complexes enable dynamic interactions with a branched polypeptide, poly(Asp-Lys)-b-Asp, which acts as a biodegradable gatekeeper.
Upon drug loading into the mesopores, the polypeptide coating retains cargo through multivalent coordination, while also enabling luminescence resonance energy transfer (LRET) between the UCNP and drug molecules, leading to visible emission quenching. Triggered by ATP-abundant in cancer and stem cells-competitive displacement of the polypeptide from TDPA-Zn²⁺ occurs, releasing the drug and restoring UCNP luminescence. This ratiometric luminescence recovery enables real-time visualization of intracellular drug release kinetics.
The biocompatible UCNP@MSN platform supports long-term tracking under 980 nm excitation and is adaptable for targeting applications. To address potential thermal effects from 980 nm irradiation, future designs may incorporate 808 nm-excitable UCNPs for enhanced biosafety. This smart nanoplatform offers great promise in cancer therapy and neural stem cell research, bridging stimuli-responsiveness with noninvasive imaging and controlled drug delivery.
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