One-Pot Synthesis of Dual Stimulus-Responsive Degradable Hollow Hybrid Nanoparticles for Image-Guided Trimodal Therapy

• Published in: Advanced functional materials Vol. 26; no. 47; pp. 8613 - 8622
• Main Authors: Hayashi, Koichiro, Maruhashi, Takuma, Nakamura, Michihiro, Sakamoto, Wataru, Yogo, Toshinobu
• Format: Journal Article
• Language: English
• Published: Blackwell Publishing Ltd 20.12.2016
• Subjects: Degradation; drug delivery systems; Drugs; Fluorescence; hybrid nanoparticles; Imaging; Nanoparticles; Singlet oxygen; stimulus-responsive degradability; theranostics; Therapy; Tumors
• ISSN: 1616-301X; 1616-3028
• DOI: 10.1002/adfm.201603394

Exploiting exogenous and endogenous stimulus‐responsive degradable nanoparticles as drug carriers can improve drug delivery systems (DDSs). The use of hollow nanoparticles may facilitate degradation, and combination of DDS with photodynamic therapy (PDT) and photothermal therapy (PTT) may enhance the anticancer effects of treatments. Here, a one‐pot synthetic method is presented for an anticancer drug (doxorubicin [DOX]) and photosensitizer‐containing hollow hybrid nanoparticles (HNPs) with a disulfide and siloxane framework formed in response to exogenous (light) and endogenous (intracellular glutathione [GSH]) stimuli. The hollow HNPs emit fluorescence within the near‐infrared window and allow for the detection of tumors in vivo by fluorescence imaging. Furthermore, the disulfides within the HNP framework are cleaved by intracellular GSH, deforming the HNPs. Light irradiation facilitates penetration of GSH into the HNP framework and leads to the collapse of the HNPs. As a result, DOX is released from the hollow HNPs. Additionally, the hollow HNPs generate singlet oxygen (1O2) and heat in response to light; thus, fluorescence imaging of tumors combined with trimodal therapy consisting of DDS, PDT, and PTT is feasible, resulting in superior therapeutic efficacy. Thus, this method may have several applications in imaging and therapeutics in the future. A one‐pot synthetic method for hollow organic–inorganic hybrid nanoparticles is described. The nanoparticles detect tumors and release anticancer drugs in response to intracellular glutathione. Additionally, the nanoparticles generate singlet oxygen and heat in response to light; thus, tumor imaging combined with trimodal therapy consisting of chemotherapy, photodynamic therapy, and photothermal therapy are feasible.