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.

Highlights

  • We report a potent multifunctional nanoplatform allowing synergistic chemo-photothermal therapy of tumors, guided by both ultrasound and photoacoustic imaging

  • This has been achieved by incorporating PFP and indocyanine green (ICG) into bio­ degradable hollow mesoporous organosilica nanoparticles

  • The pores in the hollow mesoporous organosilica nanoparticles (HMONs) were gated with a PTX prodrug, and the resultant composite subjected to PEGylation

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Summary

A Multifunctional Biodegradable Nanocomposite for Cancer Theranostics

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 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. Bubble generation typically occurs when a liquid cargo is heated to a temperature exceeding its boiling point.[27,28] Mild hyperthermia induced by photothermal conversion agents under near-infrared (NIR) irradiation is one route that can be used to vaporize the liquid.[18] For example, Shi and cow­ orkers established a multifunctional theranostic nanoplatform based on Au nanoparticle-coated hollow mesoporous silica loaded with PFH, and showed this to have applications for multimodal US/computerized tomography/photoacoustic/thermal imaging of tumors.[26]. The resultant formulation has significant potential for combined ultrasound-photoacoustic imaging guided tumor therapy, and could yield major benefits for patients

Results and Discussion
In Vitro Imaging Performance
In Vitro Bubble-Enhanced Cellular Uptake
In Vitro Therapeutic Effects
In Vivo Dual-Modality Imaging
In Vivo Pharmacokinetics and Biodistribution
In Vivo Antitumor Activity and Biosafety
Conclusions
Experimental Section
Conflict of Interest

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