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一锅法合成中空 PDA@DOX 纳米粒子用于乳腺癌的超声成像和化疗-热疗。

One-pot synthesis of hollow PDA@DOX nanoparticles for ultrasound imaging and chemo-thermal therapy in breast cancer.

机构信息

Department of Ultrasound in Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, P.R. China.

出版信息

Nanoscale. 2019 Nov 21;11(45):21759-21766. doi: 10.1039/c9nr05671h.

DOI:10.1039/c9nr05671h
PMID:31482919
Abstract

Constructing nanocarriers with high drug loading capacity is a challenge, which limits the effective delivery of drugs to solid tumors. Here, we reported a one-pot synthesis of hollow nanoparticles (NPs) encapsulated by doxorubicin (DOX) and modified with polydopamine (PDA) to form PDA@DOX NPs for breast cancer treatment. PDA@DOX NPs demonstrated exceptionally high capacity (53.16%) for loading DOX. In addition, when PDA@DOX NPs were administered systemically, they exhibited responsive aggregation in the tumor sites and demonstrated a good controlled release effect for DOX due to the weak acidic environment of the tumor sites and targeting near-infrared (NIR) light irradiation. The PDA outer layer absorbed the near-infrared (NIR) light and facilitated simultaneous generation of heat energy for destroying the tumor cells to release the drug upon NIR irradiation. Moreover, this NIR-activated combined/synergistic therapy exhibited remarkably complete tumor growth suppression in a breast cancer mouse model. Importantly, NPs exhibited a good ultrasound performance both in vitro and in vivo, which could monitor the treatment process. In conclusion, this NIR-activated PDA@DOX NP system is demonstrated as a good US-guided combination (chemotherapy + PTT) therapy platform with high loading capacity and controlled drug release characteristics, which is promising for the treatment of breast cancer.

摘要

构建具有高载药能力的纳米载体是一个挑战,这限制了药物向实体瘤的有效传递。在这里,我们报告了一种一锅法合成的载有阿霉素(DOX)并被聚多巴胺(PDA)修饰的空心纳米颗粒(NPs),以形成用于乳腺癌治疗的 PDA@DOX NPs。PDA@DOX NPs 表现出异常高的 DOX 载药能力(53.16%)。此外,当 PDA@DOX NPs 被系统给药时,它们在肿瘤部位表现出响应性聚集,并由于肿瘤部位的弱酸性环境和近红外(NIR)光照射的靶向作用,表现出良好的 DOX 控制释放效果。PDA 外层吸收近红外(NIR)光,并促进热能的同时产生,以在 NIR 照射时破坏肿瘤细胞并释放药物。此外,这种 NIR 激活的联合/协同治疗在乳腺癌小鼠模型中表现出显著的完全肿瘤生长抑制作用。重要的是,NP 在体外和体内均表现出良好的超声性能,可监测治疗过程。总之,该 NIR 激活的 PDA@DOX NP 系统被证明是一种具有高载药能力和控制药物释放特性的良好的超声引导联合(化疗+PTT)治疗平台,有望用于治疗乳腺癌。

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