ROS-responsive glycol chitosan-linked prodrug nanoparticle as a nanoplatform for tumor chemo-photodynamic therapy.

IF 2.6 4区医学 Q2 PHARMACOLOGY & PHARMACY Pharmaceutical Development and Technology Pub Date : 2024-11-01 Epub Date: 2024-09-30 DOI:10.1080/10837450.2024.2411027

Jingmou Yu, Mengqi Liu, Chao Zhang, Lizhen Cheng, Changchun Peng, Dengzhao Jiang, Wenbo Liu, Hongguang Jin, Jin Ren

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Abstract

Herein, we designed and synthesized novel reactive oxygen species (ROS)-responsive glycol chitosan-doxorubicin (DOX) prodrug via a ROS-cleavable thioketal (TK) linker. The obtained GC-TK-DOX formed self-assembled nanoparticles of 312 nm in aqueous media. Photosensitizers zinc phthalocyanine (ZnPc)-loaded GC-TK-DOX (GC-TK-DOX/ZnPc) nanoparticles were fabricated by using a dialysis approach. The GC-TK-DOX and GC-TK-DOX/ZnPc nanoparticles were nearly spherical by transmission electron microscopy (TEM) observation. Under 660-nm laser irradiation, GC-TK-DOX/ZnPc could generate singlet oxygen. Further, GC-TK-DOX/ZnPc nanoparticles exhibited ROS-sensitive release of DOX and ZnPc in vitro. GC-TK-DOX/ZnPc with laser irradiation showed more drug uptake and higher cytotoxic effects than GC-TK-DOX/ZnPc without irradiation, free DOX and GC-TK-DOX in HeLa tumor cells. Overall, these findings suggested that GC-TK-DOX/ZnPc could be a promising nanoarchitecture for synergetic chemo-photodynamic therapy against tumors.

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响应 ROS 的乙二醇壳聚糖连接原药纳米粒子作为肿瘤化疗光动力疗法的纳米平台。

在此，我们通过可被 ROS 分解的硫酮（TK）连接体设计并合成了新型活性氧（ROS）响应型乙二醇壳聚糖-多柔比星（DOX）原药。获得的 GC-TK-DOX 在水介质中形成了 312 纳米的自组装纳米颗粒。光敏剂酞菁锌（ZnPc）负载的 GC-TK-DOX （GC-TK-DOX/ZnPc）纳米粒子是通过透析方法制成的。透射电子显微镜（TEM）观察发现，GC-TK-DOX 和 GC-TK-DOX/ZnPc 纳米粒子接近球形。在 660 纳米激光照射下，GC-TK-DOX/ZnPc 可产生单线态氧。此外，GC-TK-DOX/ZnPc 纳米粒子在体外表现出对 ROS 敏感的 DOX 和 ZnPc 释放。与未经辐照的 GC-TK-DOX/ZnPc 纳米颗粒、游离 DOX 和 GC-TK-DOX 相比，经激光照射的 GC-TK-DOX/ZnPc 纳米颗粒在 HeLa 肿瘤细胞中表现出更高的药物吸收率和细胞毒性效应。总之，这些研究结果表明，GC-TK-DOX/ZnPc 是一种很有前景的纳米结构，可用于协同化疗和光动力疗法。

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来源期刊

Pharmaceutical Development and Technology 医学-药学

CiteScore

5.90

自引率

2.90%

发文量

审稿时长

1 months

期刊介绍： Pharmaceutical Development & Technology publishes research on the design, development, manufacture, and evaluation of conventional and novel drug delivery systems, emphasizing practical solutions and applications to theoretical and research-based problems. The journal aims to publish significant, innovative and original research to advance the frontiers of pharmaceutical development and technology. Through original articles, reviews (where prior discussion with the EIC is encouraged), short reports, book reviews and technical notes, Pharmaceutical Development & Technology covers aspects such as: -Preformulation and pharmaceutical formulation studies -Pharmaceutical materials selection and characterization -Pharmaceutical process development, engineering, scale-up and industrialisation, and process validation -QbD in the form a risk assessment and DoE driven approaches -Design of dosage forms and drug delivery systems -Emerging pharmaceutical formulation and drug delivery technologies with a focus on personalised therapies -Drug delivery systems research and quality improvement -Pharmaceutical regulatory affairs This journal will not consider for publication manuscripts focusing purely on clinical evaluations, botanicals, or animal models.