Biodegradable Black Phosphorus Nanosheets Mediate Specific Delivery of hTERT siRNA for Synergistic Cancer Therapy
Biodegradable Black Phosphorus Nanosheets Mediate Specific Delivery of hTERT siRNA for Synergistic Cancer Therapy
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可生物降解的黑磷纳米片介导 hTERT siRNA 的特异性递送，用于协同癌症治疗。
DOI：
10.1021/acsami.8b04807
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发表时间：
2018-06-27
影响因子：
9.5
通讯作者：
Yu, Songtao
中科院分区：
文献类型：
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作者：
Chen, Lei;Chen, Chuan;Yu, Songtao
人端粒酶逆转录酶（Human telomerase reverse transcriptase，hTERT）与肿瘤的转化、生长和转移密切相关。因此，hTERT小干扰RNA（siRNA）的递送是癌症基因治疗的重要途径。然而，基因沉默的单一抗癌作用往往受到siRNA递送和释放的低特异性或低效率的限制。在这项工作中，我们提出了小而薄的黑磷（BP）纳米片作为hTERT siRNA的可生物降解的递送系统。用聚（乙二醇）（PEG）和聚乙烯亚胺（PEI）修饰（PPBP）制备的BP纳米片表现出高siRNA负载能力和稳健的细胞摄取。当暴露于不同波长的激光照射时，PPBP纳米片也表现出有效的光动力疗法/光热疗法（PDT/PTT）活性。更重要的是，PPBP纳米片在低pH和富含活性氧（ROS）的环境中呈现逐渐降解。局部和微创PDT治疗后PPBP的降解增强，这是由于过量的ROS产生。通过PEI辅助的从酸性溶酶体的逃逸实现siRNA到细胞质的进一步递送和释放以用于基因沉默。因此，PPBP-siRNA通过特异性递送hTERT siRNA以及靶向基因治疗、PTT和PDT的协同组合有效地抑制肿瘤生长和转移。
Human telomerase reverse transcriptase (hTERT) has been found to be closely related to tumor transformation, growth, and metastasis. Thus, the delivery of hTERT small interfering RNA (siRNA) is an important approach for cancer gene therapy. However, the single anticancer effect of gene silencing is often limited by poor specificity or low efficiency in siRNA delivery and release. In this work, we present small and thin black phosphorus (BP) nanosheets as a biodegradable delivery system for hTERT siRNA. The BP nanosheets prepared with poly(ethylene glycol) (PEG) and polyethylenimine (PEI) modification (PPBP), exhibited high siRNA loading capacity and robust cell uptake. The PPBP nanosheets also exhibited potent photodynamic therapy/photothermal therapy (PDT/PTT) activities when exposed to different wavelengths of laser irradiation. More importantly, PPBP nanosheets underwent a gradual degradation when presented in a mixture of low pH and reactive oxygen species (ROS)-rich environment. The degradation of PPBP was strengthened especially after local and minimal invasive PDT treatment, because of excessive ROS production. Further delivery and release of siRNA to the cytoplasm for gene silencing was achieved by PEI-aided escape from the acidic lysosome. Thus, PPBP-siRNA efficiently inhibited tumor growth and metastasis by specific delivery of hTERT siRNA and a synergistic combination of targeted gene therapy, PTT and PDT.