Journal
JOURNAL OF CONTROLLED RELEASE
Volume 258, Issue -, Pages 95-107Publisher
ELSEVIER
DOI: 10.1016/j.jconrel.2017.05.011
Keywords
Co-self-assembly; Small molecular nanodrugs; Combination chemo-photothermal therapy; Dual-modal imaging; Epirubicin; Indocyanine green
Funding
- National Natural Science Foundation of China [21502007, 81472458, 31300285, 31100717]
- China Postdoctoral Science Foundation [2016 M602074]
- Medical Innovation Project of Fujian Province [2014-CXB-350]
- Natural Science Foundation of Fujian Province [2015 J01348]
- Project of Xiamen Science and Technology Bureau [3502Z20163004]
- Social Development Guidance (Key) Project of Fujian Province [2014Y0074]
- Specialized Research Fund for the Doctoral Program of Higher Education [20110073120072]
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Multimodal imaging-guided synergistic combination therapy has shown great potential for cancer treatment. However, the nanocarrier-based theranostic systems suffer from batch-to-batch variation, complexity of multicomponent, poor drug loading, and carrier-related toxicity issues. To address these issues, herein we developed a novel carrier-free theranostic system with nanoscale characteristics for near-infrared fluorescence (NIRF) and photoacoustic (PA) dual-modal imaging-guided synergistic chemo-photothermal therapy (PTT). Indocyanine green (ICG) and epirubicin (EPI) could co-self-assemble into small molecular nanoparticles (NPs) in aqueous solution without any molecular precursor or excipient via collaborative interactions (electrostatic, pi-pi stacking, and hydrophobic interactions). The exceptionally high dual-drug loading (similar to 92 wt%) ICG-EPI NPs showed good physiological stability, preferable photothermal response, excellent NIRF/PA imaging properties, pH-/photo-responsive drug release behavior, and promoted cellular endocytosis compared with free ICG or EPI. Importantly, the ICG-EPI NPs showed excellent tumor targeting ability with high spatial resolution and deep penetration via in vivo NIRF/PA dual-modal imaging. Moreover, in comparison with individual chemotherapy or PTT, the combinational chemo-PTT therapy of ICG-EPI NPs with NIR laser irradiation synergistically induced apoptosis and death of cancer cells in vitro, and showed synergistic chemo-PTT efficiency in vivo as evidenced by highly efficient tumor ablation. Furthermore, the ICG-EPI NPs exhibited inappreciable toxicity. This co-selfassembly of both FDA-approved agents provides a safe and Molecular economical strategy in the rational design of multifunctional nano-theranostic systems for real-time self-monitoring intracellular drug delivery and targeting multimodal imaging-guided synergistic combination therapy.
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