Development of a Light-Controlled Nanoplatform for Direct Nuclear Delivery of Molecular and Nanoscale Materials
| Autor: | Fu-Gen Wu, Hao-Ran Jia, Nathan W. Ulrich, Zhan Chen, Ya-Xuan Zhu, Guang Yu Pan |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Fluorescence-lifetime imaging microscopy
Light Cell Survival Nanoparticle Nanotechnology Docetaxel 02 engineering and technology 010402 general chemistry 01 natural sciences Biochemistry Catalysis Polyethylene Glycols Nanomaterials chemistry.chemical_compound Drug Delivery Systems Colloid and Surface Chemistry Cell Line Tumor Polyamines medicine Humans Organosilicon Compounds Photosensitizer Particle Size Nuclear membrane Fluorescent Dyes Cell Nucleus Rose Bengal Singlet oxygen technology industry and agriculture General Chemistry 021001 nanoscience & nanotechnology 0104 chemical sciences Membrane medicine.anatomical_structure chemistry Nanoparticles Camptothecin Taxoids Nanocarriers 0210 nano-technology |
| Zdroj: | Journal of the American Chemical Society. 140:4062-4070 |
| ISSN: | 1520-5126 0002-7863 |
| DOI: | 10.1021/jacs.7b13672 |
| Popis: | Research on nanomedicines has rapidly progressed in the past few years. However, due to the limited size of nuclear pores (9-12 nm), the nuclear membrane remains a difficult barrier to many nucleus-targeting agents. Here, we report the development of a general platform to effectively deliver chemical compounds such as drug molecules or nanomaterials into cell nuclei. This platform consists of a polyamine-containing polyhedral oligomeric silsesquioxane (POSS) unit, a hydrophilic polyethylene glycol (PEG) chain, and the photosensitizer rose bengal (RB), which can self-assemble into nanoparticles (denoted as PPR NPs). Confocal fluorescence imaging showed that PPR NPs mainly located in lysosomes after cellular internalization. After mild light irradiation, however, PPR NPs effectively disrupted lysosomal structures by singlet oxygen (1O2) oxidation and substantially accumulated on nuclear membranes, which enabled further disruption of the membrane integrity and promoted their final nuclear entry. Next, we selected two chemotherapeutic agents (10-hydroxycamptothecine and docetaxel) and a fluorescent dye (DiD) as payloads of PPR NPs and successfully demonstrated that this nanocarrier could efficiently deliver them into cell nuclei in a light-controlled manner. In addition to molecular compounds, we have also demonstrated that PPR NPs could facilitate the nuclear entry of nanomaterials, including Prussian blue NPs as well as gold nanorods. Compared to traditional strategies for nuclear delivery, this highly controllable nanoplatform avoids complicated modification of nucleus-targeting ligands and is generally applicable to both molecular compounds and nanomaterials. |
| Databáze: | OpenAIRE |
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