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Near-Infrared Organic Fluorescent Nanoparticles for Long-term Monitoring and Photodynamic Therapy of Cancer.

ABSTRACT: Photodynamic therapy (PDT), which utilizes reactive oxygen species to ablate tumor, has attracted much attention in recent years. Photosensitizers with near-infrared (NIR) fluorescence as well as efficient ROS generation ability have been used for precise diagnosis and simultaneous treatment of cancer. However, photosensitizers frequently suffer from low ROS generation ability and NIR fluorescence quenching in aqueous media due to the aggregation. Methods: We prepare an effective AIE active NIR emissive photosensitizer containing rhodanine as electron acceptor and triphenylvinylthiophene as electron donor is prepared, and encapsulate the corresponding photosensitizer into Pluronic F127 to fabricate NIR organic fluorescent nanoparticles. We then evaluate the NIR fluorescence bioimaging and photodynamic therapy ability of TPVTR dots in vitro and in vivo. Results: The yielded organic fluorescent nanoparticles exhibit effective ROS generation ability, bright NIR emission, high photostability, and good biocompatibility. Both in vitro and in vivo experiments confirm that NIR organic fluorescent nanoparticles demonstrate good performances in long-term tracing and photodynamic ablation of tumor. Conclusion: In summary, the synthesized organic fluorescent nanoparticles, TPVTR dots, showed great potentials in long-term cell tracing and photodynamic therapy of tumor. Our study highlights the efficient strategy for developing promising near-infrared organic fluorescent nanoparticles in advancing the field of bioimaging and further image-guide clinical applications.

SUBMITTER: Xia Q

PROVIDER: S-EPMC6470342 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Near-Infrared Organic Fluorescent Nanoparticles for Long-term Monitoring and Photodynamic Therapy of Cancer.

Xia Qi Q Chen Zikang Z Zhou Yuping Y Liu Ruiyuan R

Nanotheranostics 20190402 2

Photodynamic therapy (PDT), which utilizes reactive oxygen species to ablate tumor, has attracted much attention in recent years. Photosensitizers with near-infrared (NIR) fluorescence as well as efficient ROS generation ability have been used for precise diagnosis and simultaneous treatment of cancer. However, photosensitizers frequently suffer from low ROS generation ability and NIR fluorescence quenching in aqueous media due to the aggregation. <b>Methods</b>: We prepare an effective AIE acti ...[more]

PMID: 31008024

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Project description:Water-soluble upconversion nanoparticles (UCNPs) that exhibit significant ultraviolet, blue, and red emissions under 980-nm laser excitation were successfully synthesized for performing near infrared (NIR)-triggered photodynamic therapy (PDT). The lanthanide-doped UCNPs bearing oleate ligands were first exchanged by citrates to generate polyanionic surfaces and then sequentially encapsulated with NH?-terminated poly(amido amine) (PAMAM) dendrimers (G4) and chlorine6 (Ce6) using a layer-by-layer (LBL) absorption strategy. Transmission electron microscopy and X-ray diffraction analysis confirm that the hybrid UCNPs possess a polygonal morphology with an average dimension of 16.0 ± 2.1 nm and ?-phase crystallinity. A simple calculation derived through thermogravimetric analysis revealed that one polycationic G4 dendrimer could be firmly accommodated by approximately 150 polyanionic citrates through multivalent interactions. Moreover, zeta potential measurements indicated that the LBL fabrication results in the hybrid nanoparticles with positively charged surfaces originated from these dendrimers, which assist the cellular uptake in biological specimens. The cytotoxic singlet oxygen based on the photosensitization of the adsorbed Ce6 through the upconversion emissions can be readily accumulated by increasing the irradiation time of the incident lasers. Compared with that of 660-nm lasers, NIR-laser excitation exhibits optimized in vitro PDT effects toward human breast cancer MCF-7 cells cultured in the tumorspheres, and less than 40% of cells survived under a low Ce6 dosage of 2.5 × 10-7 M. Fluorescence microscopy analysis indicated that the NIR-driven PDT causes more effective destruction of the cells located inside spheres that exhibit significant cancer stem cell or progenitor cell properties. Moreover, an in vivo assessment based on immunohistochemical analysis for a 4T1 tumor-bearing mouse model confirmed the effective inhibition of cancer cell proliferation through cellular DNA damage by the expression of Ki67 and ?H2AXser139 protein markers. Thus, the hybrid UCNPs are a promising NIR-triggered PDT module for cancer treatment.

Project description:IntroductionDespite significant progress in the field of oncology, cancer remains one of the leading causes of death. Chemotherapy is one of the most common treatment options for cancer patients but is well known to result in off-target toxicity. Theranostic nanomedicines that integrate diagnostic and therapeutic functions within an all-in-one platform can increase tumor selectivity for more effective chemotherapy and aid in diagnosis and monitoring of therapeutic responses.Material and methodsIn this work, theranostic nanoparticles were synthesized with commonly used biocompatible and biodegradable polymers and used as cancer contrast and therapeutic agents for optical imaging and treatment of breast cancer. These core-shell nanoparticles were prepared by nanoprecipitation of blends of the biodegradable and biocompatible amphiphilic copolymers poly(lactic-co-glycolic acid)-b-poly-l-lysine and poly(lactic acid)-b-poly(ethylene glycol). Poly-l-lysine in the first copolymer was covalently decorated with near-infrared fluorescent Alexa Fluor 750 molecules.ResultsThe spherical nanoparticles had an average size of 60-80 nm. The chemotherapeutic drug doxorubicin was encapsulated in the core of nanoparticles at a loading of 3% (w:w) and controllably released over a period of 30 days. A 33-fold increase in near-infrared fluorescence, mediated by protease-mediated cleavage of the Alexa Fluor 750-labeled poly-l-lysine on the surface of the nanoparticles, was observed upon interaction with the model protease trypsin. The cytocompatibility of drug-free nanoparticles and growth inhibition of drug-loaded nanoparticles on MDA-MB-231 breast cancer cells were investigated with a luminescence cell-viability assay. Drug-free nanoparticles were found to cause minimal toxicity, even at high concentrations (0.2-2,000 µg/mL), while doxorubicin-loaded nanoparticles significantly reduced cell viability at drug concentrations >10 µM. Finally, the interaction of the nanoparticles with breast cancer cells was studied utilizing fluorescence microscopy, demonstrating the potential of the nanoparticles to act as near-infrared fluorescence optical imaging agents and drug-delivery carriers.ConclusionDoxorubicin-loaded, enzymatically activatable nanoparticles of less than 100 nm were prepared successfully by nanoprecipitation of copolymer blends. These nanoparticles were found to be suitable as controlled drug delivery systems and contrast agents for imaging of cancer cells.

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Near-Infrared Organic Fluorescent Nanoparticles for Long-term Monitoring and Photodynamic Therapy of Cancer.

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Near-Infrared Organic Fluorescent Nanoparticles for Long-term Monitoring and Photodynamic Therapy of Cancer.

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