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A Multifunctional Biodegradable Nanocomposite for Cancer Theranostics.

ABSTRACT: Theranostic formulations, integrating both diagnostic and therapeutic functions into a single platform, hold great potential for precision medicines. In this work, a biodegradable theranostic based on hollow mesoporous organosilica nanoparticles (HMONs) is reported and explored for ultrasound/photoacoustic dual-modality imaging guided chemo-photothermal therapy of cancer. The HMONs prepared are endowed with glutathione-responsive biodegradation behavior by incorporating disulfide bonds into their framework. The nanoparticles are loaded with indocyanine green (ICG) and perfluoropentane (PFP). The former acts as a photothermal agent and the latter can generate bubbles for ultrasound imaging. A paclitaxel prodrug is developed to both serve as a redox-sensitive gatekeeper controlling ICG release from the HMON pores and a chemotherapeutic. ICG generates mild hyperthermia upon exposure to an 808 nm laser, and this in turn leads to a liquid-gas phase transition of PFP, resulting in the generation of bubbles which can be used for ultrasound imaging. The platform is found to have excellent properties for both ultrasound and photoacoustic imaging. In addition, both in vitro and in vivo results show that the nanoparticles provide potent synergistic chemo-photothermal therapy. The material developed in this work thus has great potential for exploitation in advanced cancer therapies.

SUBMITTER: Wu J

PROVIDER: S-EPMC6661946 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Optical nanomaterials with intense absorption in near-infrared (NIR) region hold great promise for biomedical applications such as photothermal therapy (PTT) and photoacoustic imaging (PAI). In this work, we report mesoporous carbon nanospheres (Meso-CNs) with broadband and intense absorption in the UV-Vis-NIR region (300-1400 nm) and explore their potential as a multifunctional platform for photoacoustic imaging and chemo-photothermal therapy. Methods: Meso-CNs were prepared by a "silica-assisted" synthesis strategy and characterized by transmission electron microscope and optical spectroscopy. We investigated the photothermal conversion and photoacoustic imaging of Meso-CNs in comparison with single-walled carbon nanotubes (SWCNTs), graphene and gold nanorods (GNRs). In vitro cellular assays and in vivo chemo-photothermal combination therapy were performed. Results: The absorption coefficients of Meso-CNs are 1.5-2 times higher than those of SWCNTs and graphene and are comparable to those of GNRs in both the first and the second near-infrared optical windows (NIR-I and NIR-II) of tissues. When exposed to an NIR laser, the photothermal and photoacoustic signal generation of Meso-CNs are also stronger than those of SWCNTs, graphene, and GNRs. DOX was loaded into Meso-CNs with a high efficiency (35 wt%) owing to the unique mesoporous structure. Particularly, the drug release from Meso-CNs is sensitive to both pH and NIR light stimulation. In vivo chemo-photothermal combination therapy demonstrates a remarkable inhibition effect on tumor growth under NIR laser treatment. Conclusions: We have developed Meso-CNs for photothermal conversion and photoacoustic imaging. The porous structure also serves as a drug carrier and the drug release can be controlled by pH and external light. The high drug loading capacity, superior photothermal and photoacoustic generation, together with the apparent chemo-photothermal therapeutic effect, make Meso-CNs a promising platform for cancer theranostics.

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A Multifunctional Biodegradable Nanocomposite for Cancer Theranostics.

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