ABSTRACT
Nanotechnology has emerged as a promising solution to permanent elimination of cancer. However, nanoparticles themselves lack specificity to tumors. Due to enhanced migration to tumors, mesenchymal stem cells (MSCs) were suggested as cell-mediated delivery vehicles of nanoparticles. In this study, we have constructed a complex composed of photoluminescent quantum dots (QDs) and a photosensitizer chlorin e6 (Ce6) to obtain multifunctional nanoparticles, combining cancer diagnostic and therapeutic properties. QDs serve as energy donors-excited QDs transfer energy to the attached Ce6 via Förster resonance energy transfer, which in turn generates reactive oxygen species. Here, the physicochemical properties of the QD-Ce6 complex and singlet oxygen generation were measured, and the stability in protein-rich media was evaluated, showing that the complex remains the most stable in protein-free medium. In vitro studies on MSC and cancer cell response to the QD-Ce6 complex revealed the complex-loaded MSCs' potential to transport theranostic nanoparticles and induce cancer cell death. In vivo studies proved the therapeutic efficacy, as the survival of tumor-bearing mice was statistically significantly increased, while tumor progression and metastases were slowed down.
Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Lewis Lung/diagnostic imaging , Carcinoma, Lewis Lung/drug therapy , Mesenchymal Stem Cells/metabolism , Multifunctional Nanoparticles/therapeutic use , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/metabolism , Antineoplastic Agents/radiation effects , Cadmium Compounds/chemistry , Cadmium Compounds/metabolism , Cadmium Compounds/radiation effects , Cadmium Compounds/therapeutic use , Carcinoma, Lewis Lung/metabolism , Cell Line, Tumor , Chlorophyllides/chemistry , Chlorophyllides/metabolism , Chlorophyllides/radiation effects , Chlorophyllides/therapeutic use , Female , Humans , Light , Mice, Inbred C57BL , Multifunctional Nanoparticles/chemistry , Multifunctional Nanoparticles/metabolism , Multifunctional Nanoparticles/radiation effects , Photochemotherapy/methods , Photosensitizing Agents/chemistry , Photosensitizing Agents/metabolism , Photosensitizing Agents/radiation effects , Photosensitizing Agents/therapeutic use , Precision Medicine/methods , Quantum Dots/chemistry , Quantum Dots/metabolism , Quantum Dots/radiation effects , Quantum Dots/therapeutic use , Selenium Compounds/chemistry , Selenium Compounds/metabolism , Selenium Compounds/radiation effects , Selenium Compounds/therapeutic use , Singlet Oxygen/metabolism , Sulfides/chemistry , Sulfides/metabolism , Sulfides/radiation effects , Sulfides/therapeutic use , Zinc Compounds/chemistry , Zinc Compounds/metabolism , Zinc Compounds/radiation effects , Zinc Compounds/therapeutic useABSTRACT
Inspired by the natural motors, artificial nanomotors (NMs) have emerged as intelligent, advanced, and multifunctional nanoplatforms that can perform complex tasks in living environments. However, the functionalization of these fantastic materials is in its infancy, hindering the success of this booming field. Herein, an inhibitor-conjugated near-infrared (NIR) laser-propelled Janus nanomotor (JNM-I) was constructed and first applied in the modulation of amyloid-ß protein (Aß) aggregation which is highly associated with Alzheimer's disease (AD). Under NIR light illumination, JNM-I exhibited efficient propulsion through the "self-thermophoresis" effect, and the active motion of JNM-I increased the opportunity of the contacts between the immobilized inhibitors and Aß species, leading to an intensification of JNM-I on modulating the on-pathway Aß aggregation, as evidenced by the distinct changes of the amyloid morphology, conformation, and cytotoxicity. For example, with a NIR irradiation, 200 µg/mL of JNM-I increased the cultured SH-SY5Y cell viability from 68% to nearly 100%, but it only protected the cells to 89% viability without an NIR irradiation. Meanwhile, the NIR irradiation effectively improved the blood-brain barrier (BBB) penetration of JNM-I. Such a JNM-I has connected artificial nanomotors with protein aggregation and provided new insight into the potential applications of various nanomotors in the prevention and treatment of AD.
Subject(s)
Amyloid beta-Peptides , Multifunctional Nanoparticles , Alzheimer Disease , Amyloid/antagonists & inhibitors , Amyloid/chemistry , Amyloid/metabolism , Amyloid beta-Peptides/antagonists & inhibitors , Amyloid beta-Peptides/chemistry , Amyloid beta-Peptides/metabolism , Benzothiazoles , Blood-Brain Barrier/drug effects , Blood-Brain Barrier/metabolism , Cell Line, Tumor , Cell Survival/drug effects , Humans , Infrared Rays , Models, Biological , Multifunctional Nanoparticles/chemistry , Multifunctional Nanoparticles/radiation effectsABSTRACT
As a member of flavonoids, the application of quercetin has been mainly focused on antioxidation study. Fabrication of multifunctional nanoplatforms with quercetin is limited. In the present study, water-soluble quercetin derived nanoparticles (QFNPs) were fabricated through the one pot synthesis strategy with Fe3+, quercetin and poly (vinyl pyrrolidone) (PVP). The raw materials were dissolved in absolute ethanol and the mixed together. After stirring at room temperature for 6â¯h, the QFNPs could be simply harvested by centrifugation without the need of time-consuming dialysis procedure. Due to the protective effect of PVP, the synthesized nanoparticles could be well dispersed in water with the hydrodynamic size about 23â¯nm. DPPH free radical scavenging capacity assay showed QFNPs could act as efficient antioxidant. Besides antioxidation activity, the QFNPs also exhibited good photothermal capacity. Temperature stability result suggested the good stability of QFNPs between 35 and 95⯰C. MTT and hemolysis assay showed the good biocompatibility of QFNPs. What's more, the QFNPs showed good cellular antioxidation activity and efficient photothermal killing effect to cancer cells (4T1 cells). The QFNPs could be promising nanoplatform for biomedical application.
