Department of Chemistry of The College of Staten Island, The City University of New York , Staten Island, New York 10314, United States.
Ph.D. Program in Biochemistry and Chemistry, The Graduate Center, The City University of New York , New York, New York 10016, United States.
ACS Appl Mater Interfaces. 2017 Jun 7;9(22):18639-18649. doi: 10.1021/acsami.7b06062. Epub 2017 May 22.
Multifunctional nanocarriers with good biocompatibility, good imaging function, and smart drug delivery ability are crucial for realizing highly efficient imaging-guided chemotherapy in vivo. This paper reports a type of chitosan-carbon dot (CD) hybrid nanogels (CCHNs, ∼65 nm) by integrating pH-sensitive chitosan and fluorescent CDs into a single nanostructure for simultaneous near-infrared (NIR) imaging and NIR/pH dual-responsive drug release to improve therapeutic efficacy. Such CCHNs were synthesized via a nonsolvent-induced colloidal nanoparticle formation of chitosan-CD complexes assisted by ethylenediaminetetraacetic acid (EDTA) molecules in the aqueous phase. The selective cross-linking of chitosan chains in the nanoparticles can immobilize small CDs complexed in the chitosan networks. The resultant CCHNs display high colloidal stability, high loading capacity for doxorubicin (DOX), bright and stable fluorescence from UV to NIR wavelength range, efficient NIR photothermal conversion, and intelligent drug release in response to both NIR light and change in pH. The results from in vitro tests on cell model and in vivo tests on different tissues of animal model indicate that the CCHNs are nontoxic. The DOX-loaded CCHNs can permeate into the implanted tumor on mice and release drug molecules efficiently on site to inhibit tumor growth. The additional photothermal treatments from NIR irradiation can further inhibit the tumor growth, benefited from the effective NIR photothermal conversion of CCHNs. The demonstrated CCHNs manifest a great promise toward multifunctional intelligent nanoplatform for highly efficient imaging-guided cancer therapy with low side effects.
多功能纳米载体具有良好的生物相容性、良好的成像功能和智能药物输送能力，对于实现高效的体内成像引导化疗至关重要。本文报道了一种壳聚糖-碳点（CD）杂化纳米凝胶（CCHNs，约 65nm），通过将 pH 敏感的壳聚糖和荧光 CD 整合到单个纳米结构中，实现了近红外（NIR）成像和 NIR/pH 双重响应药物释放，以提高治疗效果。这种 CCHNs 是通过壳聚糖-CD 配合物在水溶液中在乙二胺四乙酸（EDTA）分子的辅助下，通过非溶剂诱导胶体纳米颗粒形成来合成的。纳米颗粒中壳聚糖链的选择性交联可以固定在壳聚糖网络中复合的小 CD。所得的 CCHNs 表现出高胶体稳定性、高阿霉素（DOX）负载能力、从紫外到近红外波长范围的明亮和稳定荧光、高效的近红外光热转换以及对 NIR 光和 pH 变化的智能药物释放。细胞模型的体外测试和不同动物模型组织的体内测试结果表明，CCHNs 无毒。负载 DOX 的 CCHNs 可以渗透到小鼠植入的肿瘤中，并在现场有效释放药物分子，以抑制肿瘤生长。额外的近红外光热治疗可以进一步抑制肿瘤生长，这得益于 CCHNs 的有效近红外光热转换。所展示的 CCHNs 为高效的成像引导癌症治疗提供了一种多功能智能纳米平台，具有低副作用的潜力。
