1. Micelles assembled with carbocyanine dyes for theranostic near-infrared fluorescent cancer imaging and photothermal therapy
Hong Yang,1 Huajian Mao,1 ZhihuiWan, Aijun Zhua, Miao Guo, Yanli Li, Xinming Li, Jiangling Wan, Xiangliang Yang, Xintao Shuai, Huabing Chen*
Biomaterials, 2013, 34, 9124-9133(IF=7.604)
Abstract: It is an emerging focus to explore a theranostic nanocarrier for simultaneous cancer imaging and therapy. Herein, we demonstrate a theranostic micelle system for cancer near infrared fluorescent (NIRF) imaging with enhanced signal to noise ratio and superior photothermal therapy. The copolymers consisting of monomethoxy poly(ethylene glycol) and alkylamine-grafted poly(L-aspartic acid) are assembled with carbocyanine dyes into theranostic micelles, which exhibit small size, high loading capacity, good stability, sustained release behavior, and enhanced cellular uptake. The micelles achieve the preferable biodistribution and long-term retention of carbocyanine dyes at tumor, which result in enhanced NIRF imaging by generating stable retention of NIRF signals at both hypervascular and hypovascular tumors during a long-term imaging period of up to 8 day, ccompanying with negligible noise at normal tissues. The photostability of carbocyanine dye (Cypate) plays an important role for long-term cancer imaging with enhanced SNR. Moreover, the micelles exhibit severe photothermal damage on cancer cells via the destabilization of subcellular organelles upon photoirradiation, causing superior photothermal tumor regress. The micelles act as a powerful theranostic nanocarrier for simultaneous cancer imaging with high contrast and superior photothermal therapy.
2. Highly efficient hierarchical micelles integrating photothermal therapy and singlet oxygen-synergized chemotherapy for cancer eradication
Zhihui Wan,1 Huajian Mao,1 Miao Guo, Yanli Li, Aijun Zhu, Hong Yang, Hui He, Junkang Shen,
Lijuan Zhou, Zhen Jiang, Cuicui Ge, Xiaoyuan Chen, Xiangliang Yang, Gang Liu, and Huabing Chen*
Theranostics, 2014, 4, 399-411 (IF=7.806)
Abstract: It is highly desirable to develop theranostic nanoparticles for achieving cancer imaging with enhanced contrast and simultaneously multimodal synergistic therapy. Herein, we report atheranostic micelle system hierarchically assembling cyanine dye (indocyanine green) and chemotherapeutic compound (doxorubicin) (I/D-Micelles) as a novel theranostic platform with high drug loading, good stability and enhanced cellular uptake via clathrin-mediated endocytosis. I/D-Micelles exhibit the multiple functionalities including near infrared fluorescence (NIRF), hyperthermia and intracellular singlet oxygen from indocyanine green, and simultaneous cytotoxicity from doxorubicin. Upon photoirradiation, I/D-Micelles can induce NIRF imaging, acute photothermal therapy via hyperthermia and simultaneous synergistic chemotherapy via singlet oxygen-triggered disruption of lysosomal membranes, eventually leading to enhanced NIRF imaging and superior tumor eradication without any re-growth. Our results suggest that the hierarchical micelles can act as a superior theranostic platform for cancer imaging and multimodal synergistic therapy.
3. Dual imaging-guided photothermal/photodynamic therapy using micelles
Miao Guo, Huajian Mao, Yanli Li, Aijun Zhu, Hui He, Hong Yang, Yangyun Wang, Xin Tian, Cuicui Ge, Qiaoli Peng, Xiaoyong Wang, Xiangliang Yang, Xiaoyuan Chen, Gang Liu,* and Huabing Chen*
Biomaterials, 2014, In press (IF=7.604)
Abstract: We report a type of photosensitizer (PS)-loaded micelles integrating cyanine dye as potential theranostic micelles for precise anatomical tumor localization via dual photoacoustic (PA)/near-infrared fluorescent (NIRF) imaging modalities, and simultaneously superior cancer therapy via sequential synergistic photothermal therapy (PTT)/photodynamic therapy (PDT). The micelles exhibit enhanced photostability, cell internalization and tumor accumulation. The dual NIRF/PA imaging modalities of the micelles cause the high imaging contrast and spatial resolution of tumors, which provide precise anatomical localization of the tumor and its inner vasculature for guiding PTT/PDT treatments. Moreover, the micelles can generate severe photothermal damage on cancer cells and destabilization of the lysosomes upon PTT photoirradiation, which subsequently facilitate synergistic photodynamic injury via PS under PDT treatment. The sequential treatments of PTT/PDT trigger the enhanced cytoplasmic delivery of PS, which contributes to the synergistic anticancer efficacy of PS. Our strategy provides a dual-modal cancer imaging with high imaging contrast and spatial resolution, and subsequent therapeutic synergy of PTT/PDT for potential multimodal theranostic application.
4. Polyion complex vesicles for photo-induced intracellular delivery of amphiphilic photosensitizer
Huabing Chen, Ling Xiao, Yasutaka Anraku, Peng Mi, Xueying Liu, Horacio Cabral, Aki Inoue, Takahiro Nomoto, Akihiro Kishimura,* Nobuhiro Nishiyama,* Kazunori Kataoka*
J. Am. Chem. Soc., 2014, 136, 157-163 (IF=10.677)
Abstract: Polymer vesicles formed by a pair of oppositely charged poly(ethylene glycol) (PEG)-based block aniomer and homocatiomer, termed “PICsomes”, have tunable size, and are characterized by unique semipermeable property due to the flexible and tunable hydrophilicity of polyion complex (PIC) membranes. The PICsomes can encapsulate a variety of molecules in an inner aqueous phase just by a simple vortex mixing of solution, expecting their utility as nanocontainers of substances with biomedical interests. Here, we report on a new functionality of the PICsomes: photoinduced release of photoactive agents for intracellular drug delivery. A potent photosensitizer, Al(III) phthalocyanine chloride disulfonic acid (AlPcS2a), was efficiently incorporated into the PICsomes (11%(w/w)), and its quick release was induced by photoirradiation possibly due to the photochemical damage of the PIC membranes. The combination of a high-resolution fluorescent confocal microscopy and a lysosome membrane-specific staining method revealed that such photoinduced release of AlPcS2a occurred even in the lysosomes of living cells after endocytic internalization. Simultaneously, the released AlPcS2a photochemically affected the integrity of the lysosomal membranes, leading to the translocation of AlPcS2a and PICsomes themselves to the cytoplasm. Consequently, the AlPcS2a-encapsulated PICsomes (AlPcS2a-PICsomes) exhibited appreciably stronger photocytotoxicity compared with free AlPcS2a alone. Thus, the AlPcS2a-PICsomes have promising feasibility for the photodynamic therapy or the photoinduced cytoplasmic delivery of therapeutic molecules.