4.8 Article

Near-infrared boosted ROS responsive siRNA delivery and cancer therapy with sequentially peeled upconversion nano-onions

期刊

BIOMATERIALS
卷 225, 期 -, 页码 -

出版社

ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2019.119501

关键词

Upconversion nano-onions (UCNOs); Sequential response; Reactive oxygen species (ROS); siRNA delivery

资金

  1. National Natural Science Foundation of China [21635005, 21605083, 21974064]
  2. National Research Foundation for Thousand Youth Talents Plan of China
  3. Natural Science Foundation of Jiangsu Province [BK 20160644]
  4. State Key Laboratory of Analytical Chemistry for Life Science [5431ZZXM1806]
  5. Specially-appointed Professor Foundation of Jiangsu Province
  6. Program for Innovative Talents and Entrepreneurs of Jiangsu Province

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RNA interference (RNAi) therapy has become an appealing approach for cancer treatment, while the specificity and efficiency of controlled small interference RNA (siRNA) release remain challenging due to the heterogeneity of tumor environment. Herein, upconversion nano-onions (UCNOs) with stacked polymer coating layers are constructed to decompose sequentially in response to extracellular environment and NIR stimulation. The UCNOs (UCNPs-PEIRB-PEISeSe/siRNA-R8-HA) are composed of upconversion nanoparticles (UCNPs) core functionalized with inner coating layer of photosensitizer rose bengal (RB) conjugated PEI 600, middle coating layer of singlet oxygen (O-1(2)) sensitive diselenide linked PEI 600 with therapeutic siRNA loading and cell-penetrating peptide R8 modification, and outer coating layer of negatively charged hyaluronic acid (HA). HA prevents siRNA leakage during delivery process and specifically targets tumor cells with overexpressed CD44 membrane receptors, and digested by cell secreted hyaluronidase (HAase). Upon the subsequent irradiation at 808 nm, UCNPs core generates emissions around 540 nm, which activate RB to boost ROS generation for complete PEI-SeSe decompose. The NIR boosted decompose of UCNOs induces a fast and efficient siRNA release, which effectively improves the gene silencing efficiency in vitro and suppresses tumor growth in vivo. The proposed sequentially responsive UCNOs have promising potential application in precision medicine.

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