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Jalani, Ghulam, et al. Journal of the American Chemical Society 140.35 (2018): 10923-10931.
Upconverting nanoparticles (UCNPs) have emerged as a transformative material in the development of light-triggered drug delivery systems. These nanomaterials possess the unique ability to absorb near-infrared (NIR) light and emit higher-energy photons in the UV, visible, or NIR range via photon upconversion processes. This capability effectively overcomes a key limitation in conventional photoreactive systems, which rely on UV/Vis light-both of which have limited tissue penetration and can damage biological structures.
UCNPs act as internal light sources, enabling spatially and temporally controlled drug release deep within biological tissues. This makes them particularly attractive for applications such as localized anesthesia, wound healing, targeted post-surgical therapy, and cancer treatment. By incorporating UCNPs into drug-loaded nanocarriers, on-demand drug release can be remotely activated using low-energy NIR irradiation, which is noninvasive and safe for biological systems.
Recent advances have demonstrated UCNP-based systems capable of efficient drug release and concurrent bioimaging, offering dual functionality in therapeutic monitoring. However, challenges remain in improving energy transfer efficiency, minimizing toxicity, and achieving clinical-grade reproducibility. Future directions point toward optimizing UCNP composition and surface chemistry, enhancing tissue-targeting capabilities, and reducing required excitation power.
These smart nanoplatforms offer a promising path toward clinical translation, enabling precise, NIR-controlled therapies that meet the demands of modern personalized medicine.
Han, Jin-Hee, Timothy Toner, and Rico Gunawan. Journal of Immunological Methods 510 (2022): 113364.
Upconverting nanoparticles (UCNPs) have demonstrated exceptional potential as luminescent donors in luminescence resonance energy transfer (LRET)-based immunoassays. In a recent proof-of-concept study, UCNPs were employed to develop a homogeneous particle-based immunoassay enabling multiplex potency analysis of two therapeutic monoclonal antibodies (mAbs) in a fixed-combination formulation. Leveraging NIR excitation and distinct visible-range emissions, the UCNPs offered superior signal-to-noise ratios due to minimized autofluorescence and light scattering.
Two different UCNPs were conjugated with recombinant human target proteins specific to mAb1 and mAb2, respectively. A competitive binding format was used to avoid cross-reactivity-each mAb competes with a fluorophore-labeled anti-protein antibody for UCNP-bound target. This strategy yielded distinct, reverse sigmoidal dose-response curves for each mAb without signal overlap. Post-conjugation Tris treatment effectively quenched free NHS groups on UCNP surfaces, reducing non-specific interactions.
This LRET-based assay exemplifies how UCNPs can enhance assay specificity, multiplexing capacity, and analytical throughput in biopharmaceutical quality control. Given their tunable emissions, photostability, and biocompatibility, UCNPs offer a powerful platform for complex immunoassays-especially where co-formulated biologics require precise, parallel quantification. This work underscores the value of UCNPs in next-generation diagnostic and analytical technologies.
Zhou, Yanmei, et al. Biosensors and Bioelectronics 214 (2022): 114549.
Upconverting nanoparticles (UCNPs) have emerged as powerful multifunctional tools in theranostics, integrating molecular diagnostics with targeted therapy. In a recent study, a sophisticated nanodevice based on NaYF₄:Yb,Tm@NaYF₄ core-shell UCNPs was developed for intracellular detection of miRNA-21 and near-infrared (NIR)-controlled drug release. The platform utilizes DNAzyme-amplified sensing for miRNA-21, achieving high sensitivity with a detection limit of 1.8 × 10⁻¹¹ M. This enables in situ fluorescence imaging of miRNA expression in live cells, allowing precise cancer diagnosis at the molecular level.
For therapy, the UCNPs were functionalized with dual photo-cleavable linker DNA strands carrying antisense oligonucleotides (ASOs), doxorubicin (DOX), and a MUC1 aptamer for tumor targeting. Upon 980 nm NIR irradiation, UCNPs emit UV light (365 nm) to cleave the PC-linkers, releasing ASOs and DOX on demand. This light-responsive mechanism offers spatiotemporal control of chemo-gene synergistic therapy, minimizing off-target effects. The system demonstrated strong therapeutic efficacy in vitro and in vivo, particularly in MUC1-expressing cancer cells.
This dual-function UCNP-based nanoplatform exemplifies a next-generation approach in cancer theranostics-enabling real-time miRNA detection and controlled therapeutic delivery with a single construct. Its programmability and precision make it a promising candidate for clinical translation in personalized oncology.
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