Hyaluronic Acid Nanoparticles Based on a Conjugated Oligomer Photosensitizer: Target-Specific Two-Photon Imaging, Redox-Sensitive Drug Delivery, and Synergistic Chemo-Photodynamic Therapy,ACS Applied Bio Materials

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Hyaluronic Acid Nanoparticles Based on a Conjugated Oligomer Photosensitizer: Target-Specific Two-Photon Imaging, Redox-Sensitive Drug Delivery, and Synergistic Chemo-Photodynamic Therapy
ACS Applied Bio Materials ( IF 4.6 ) Pub Date : 2019-05-15 , DOI: 10.1021/acsabm.9b00130
Yan-Qin Huang ₁ , Li-Jie Sun ₁ , Rui Zhang ₂ , Jian Hu ₁ , Xing-Fen Liu ₁ , Rong-Cui Jiang ₁ , Qu-Li Fan ₁ , Lian-Hui Wang ₁ , Wei Huang _{1,

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Affiliation

Self-assembled hyaluronic acid (HA) nanoparticles have been extensively investigated as anticancer therapeutic agents due to the biocompatibility, biodegradability, and active targeting characteristics of HA. However, many HA nanoparticles are restricted to the applications in drug delivery for chemotherapy or lack effective imaging agents. Hence, we developed the camptothecin (CPT)-loaded HA-SS-BFVPBT nanoparticles (HSBNPs) as a multifunctional platform for two-photon imaging and synergistic chemo-photodynamic therapy at the same time. A novel conjugated oligomer photosensitizer, BFVPBT, which was conjugated onto HA through the redox-responsive disulfide linkage (SS), could not only provide a hydrophobic domain for the formation of nanoparticles and drug entrapment but also act as a two-photon photosensitizer that can be directly excited and simultaneously used in two-photon imaging and photodynamic therapy (PDT). HeLa cells overexpressing the HA receptor (CD44) were used for in vitro studies, which proved the specific cellular uptake of CPT-loaded HSBNPs and excellent two-photon PDT/chemotherapy synergistic effect. The nanoparticles have also been shown to realize tumor-targeting in vivo imaging in HeLa-tumor-bearing mice. Moreover, the fluorescence of CPT-loaded HSBNPs could be activated due to the degradation by the reductive glutathione (GSH) and overexpressed hyaluronidases (Hyal-1) in cancer cells, and the intracellular drug release rate was quickened, thus improving the probability of precise cancer diagnosis and therapy. Accordingly, this HSBNPs system is also anticipated to be a precise nanocarrier for other imaging and therapeutic agents besides CPT, offering a promising new avenue for imaging-guided efficient cancer therapy.

中文翻译：

基于共轭低聚物光敏剂的透明质酸纳米颗粒：靶向特异性双光子成像、氧化还原敏感药物递送和协同化学光动力疗法

由于 HA 的生物相容性、生物降解性和主动靶向特性，自组装透明质酸 (HA) 纳米颗粒作为抗癌治疗剂已被广泛研究。然而，许多透明质酸纳米粒子仅限于在化疗药物递送中的应用或缺乏有效的显像剂。因此，我们开发了负载喜树碱 (CPT) 的 HA-SS-BFVPBT 纳米粒子 (HSBNPs) 作为双光子成像和协同化学光动力治疗的多功能平台。一种新型共轭低聚物光敏剂 BFVPBT，通过氧化还原响应二硫键 (SS) 与 HA 共轭，不仅可以为纳米颗粒的形成和药物包埋提供疏水域，还可以作为双光子光敏剂，可以直接激发并同时用于双光子成像和光动力治疗（PDT）。过表达 HA 受体 (CD44) 的 HeLa 细胞用于体外研究证明了载有 CPT 的 HSBNPs 的特异性细胞摄取和优异的双光子 PDT/化疗协同效应。纳米粒子也被证明可以在荷荷荷拉瘤小鼠中实现肿瘤靶向体内成像。此外，由于还原性谷胱甘肽（GSH）和过表达的透明质酸酶（Hyal-1）在癌细胞中的降解，CPT负载的HSBNPs的荧光可以被激活，细胞内药物释放速度加快，从而提高精确的概率。癌症诊断和治疗。因此，该 HSBNPs 系统也有望成为除 CPT 之外的其他成像和治疗剂的精确纳米载体，为成像引导的有效癌症治疗提供有希望的新途径。

更新日期：2019-05-23

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