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Theranostics 2016; 6(12):2170-2182. doi:10.7150/thno.16633 This issue Cite

Research Paper

Versatile pH-response Micelles with High Cell-Penetrating Helical Diblock Copolymers for Photoacoustic Imaging Guided Synergistic Chemo-Photothermal Therapy

Shengyu Shi^1*, Yajing Liu^2*, Yu Chen¹, Zhihuang Zhang¹, Yunsheng Ding¹, Zongquan Wu¹, Jun Yin^1✉, Liming Nie^2✉

1. Department of Polymer Science and Engineering, School of Chemistry and Chemical Engineering, Hefei University of Technology and Anhui Key Laboratory of Advanced Functional Materials and Devices, Hefei, 230009, China.
2. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102, China.
*These authors contributed equally to this work.

✉ Corresponding authors: Jun Yin: yinjunedu.cn; Liming Nie: nielmedu.cn

Abstract

With high optical absorption efficiency, near infrared (NIR) dyes have been proposed as theranostic agents for fluorescence imaging, photoacoustic imaging (PAI), and photothermal therapy (PTT). However, inherent hydrophobicity and short circulation time of small molecule hinder the further biomedical application. Herein smart amphiphilic copolymer was synthesized containing IR780/camptothecin@poly(ε-caprolactone) (IR780/CPT@PCL) as core, helical poly(phenyl isocyanide) (PPI) blocks as shell with the pH-responsive rhodamine B (RhB) moieties in the core-shell interface. With hydrophilic helical PPI coronas, these micelles present significantly enhanced cell-penetrating capacity that plays a key role in facilitating intracellular delivery of various cargos. By encapsulating CPT and IR780 molecules, the multifunctional self-assemble probe has huge potential to realize functional cooperativity and adaptability for cancer diagnosis and therapy. The in vitro and in vivo experimental results demonstrate that the pH-triggered fluorescent responsiveness and strong acoustic generation permit them efficient fluorescent and PA signal sensing for cancer diagnosis. Moreover, with 808 nm laser irradiation, the generated heat significantly improves the drug release from PCL core, leading to synergetic chemo-photothermal therapy and decreases tumor recurrence rates in mice. Overall, the biocompatible multifunctional micelles with these combined advantages can potentially be utilized for PAI guided disease diagnosis and tumor ablation.

Keywords: helical poly(phenyl isocyanide), micelles, cell penetration, photoacoustic imaging, theranostics.

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