PDF(Pubmed)
Abstract：
BACKGROUND: Breast cancer ranks second as the most common malignancy globally, after lung cancer. Among the various subtypes of breast cancer, HER2 positive breast cancer (HER2 BC)poses a particularly challenging prognosis due to its heightened invasiveness and metastatic potential. The objective of this study was to construct a composite piezoelectric nanoparticle based on poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)) for imaging and treatment of HER2 BC.
METHODS: By reshaping the crystal structure of P(VDF-TrFE) piezoelectric nanoparticles, improving hydrophilicity, and incorporating imaging capabilities, we developed piezoelectric composite nanoparticles (PGd@tNBs) that integrate imaging and therapeutic functions. The in vitro characterization encompassed the assessment of piezoelectric properties, hydrophilicity, imaging performance, and therapeutic efficacy of these particles. The targeting and therapeutic effectiveness of PGd@tNBs particles were further validated in the SK-BR3 cell line and subsequently confirmed in HER2-positive tumor-bearing mice.
RESULTS: The nanoparticle demonstrated excellent biocompatibility and impressive multimodal imaging performance. Magnetic resonance imaging (MRI) observations revealed significant accumulation of PGd@tNBs particles in the HER2 positive tumor, exhibiting superior contrast-enhanced ultrasound performance compared to traditional ultrasound contrast agents, and small animal in vivo imaging showed that PGd@tNBs particles were primarily excreted through respiration and urinary metabolism. Piezoforce Microscopy characterization highlighted the outstanding piezoelectric properties of PGd@tNBs particles. Upon targeted binding to HER2-BC, ultrasound stimulation influenced the cell membrane potential, leading to reversible electroporation. This, in turn, affected the balance of calcium ions inside and outside the cells and the mitochondrial membrane potential. Following ingestion by cells, PGd@tNBs, when exposed to ultrasound, triggered the generation of reactive oxygen species (ROS), resulting in the consumption of glutathione and superoxide dismutase and achieving sonodynamic therapy. Notably, repeated ultrasound stimulation, post PGd@tNBs particles binding and entry into cells, increased ROS production and elevated the apoptosis rate by approximately 45%.
CONCLUSIONS: In conclusion, the PGd@tNBs particles developed exhibit outstanding imaging and therapeutic efficacy, holding potential for precise diagnosis and personalized treatment of HER2 BC.
METHODS: By reshaping the crystal structure of P(VDF-TrFE) piezoelectric nanoparticles, improving hydrophilicity, and incorporating imaging capabilities, we developed piezoelectric composite nanoparticles (PGd@tNBs) that integrate imaging and therapeutic functions. The in vitro characterization encompassed the assessment of piezoelectric properties, hydrophilicity, imaging performance, and therapeutic efficacy of these particles. The targeting and therapeutic effectiveness of PGd@tNBs particles were further validated in the SK-BR3 cell line and subsequently confirmed in HER2-positive tumor-bearing mice.
RESULTS: The nanoparticle demonstrated excellent biocompatibility and impressive multimodal imaging performance. Magnetic resonance imaging (MRI) observations revealed significant accumulation of PGd@tNBs particles in the HER2 positive tumor, exhibiting superior contrast-enhanced ultrasound performance compared to traditional ultrasound contrast agents, and small animal in vivo imaging showed that PGd@tNBs particles were primarily excreted through respiration and urinary metabolism. Piezoforce Microscopy characterization highlighted the outstanding piezoelectric properties of PGd@tNBs particles. Upon targeted binding to HER2-BC, ultrasound stimulation influenced the cell membrane potential, leading to reversible electroporation. This, in turn, affected the balance of calcium ions inside and outside the cells and the mitochondrial membrane potential. Following ingestion by cells, PGd@tNBs, when exposed to ultrasound, triggered the generation of reactive oxygen species (ROS), resulting in the consumption of glutathione and superoxide dismutase and achieving sonodynamic therapy. Notably, repeated ultrasound stimulation, post PGd@tNBs particles binding and entry into cells, increased ROS production and elevated the apoptosis rate by approximately 45%.
CONCLUSIONS: In conclusion, the PGd@tNBs particles developed exhibit outstanding imaging and therapeutic efficacy, holding potential for precise diagnosis and personalized treatment of HER2 BC.
摘要：
背景：乳腺癌是全球最常见的恶性肿瘤，肺癌后。在乳腺癌的各种亚型中，HER2阳性乳腺癌(HER2BC)由于其增加的侵袭性和转移潜力而提出了特别具有挑战性的预后。本研究的目的是构建基于聚（偏二氟乙烯-三氟乙烯）（P（VDF-TrFE））的复合压电纳米粒子，用于HER2BC的成像和治疗。
方法：通过重塑P（VDF-TrFE）压电纳米颗粒的晶体结构，改善亲水性，并结合成像功能，我们开发了集成成像和治疗功能的压电复合纳米粒子（PGd@tNBs）。体外表征包括对压电性能的评估，亲水性,成像性能，和这些颗粒的治疗效果。PGd@tNBs颗粒的靶向和治疗有效性在SK-BR3细胞系中进一步验证,随后在HER2阳性荷瘤小鼠中证实。
结果：纳米颗粒表现出优异的生物相容性和令人印象深刻的多模态成像性能。磁共振成像（MRI）观察显示PGd@tNBs颗粒在HER2阳性肿瘤中显著积累，与传统超声造影剂相比，具有优越的超声造影性能，和小动物体内成像显示PGd@tNBs颗粒主要通过呼吸和尿液代谢排出。压电显微镜表征强调了PGd@tNBs颗粒的出色压电性能。在靶向结合HER2-BC后，超声刺激影响细胞膜电位，导致可逆电穿孔。这个,反过来,影响细胞内外钙离子的平衡和线粒体膜电位。在被细胞摄取后，PGd@tNB,当暴露于超声波时，触发了活性氧（ROS）的产生，导致谷胱甘肽和超氧化物歧化酶的消耗，并实现声动力治疗。值得注意的是,重复超声刺激，PGd@tNBs颗粒结合并进入细胞后，增加ROS的产生并将凋亡率提高约45％。
结论：结论：开发的PGd@tNBs颗粒表现出出色的成像和治疗效果，具有精确诊断和个性化治疗HER2BC的潜力。
方法：通过重塑P（VDF-TrFE）压电纳米颗粒的晶体结构，改善亲水性，并结合成像功能，我们开发了集成成像和治疗功能的压电复合纳米粒子（PGd@tNBs）。体外表征包括对压电性能的评估，亲水性,成像性能，和这些颗粒的治疗效果。PGd@tNBs颗粒的靶向和治疗有效性在SK-BR3细胞系中进一步验证,随后在HER2阳性荷瘤小鼠中证实。
结果：纳米颗粒表现出优异的生物相容性和令人印象深刻的多模态成像性能。磁共振成像（MRI）观察显示PGd@tNBs颗粒在HER2阳性肿瘤中显著积累，与传统超声造影剂相比，具有优越的超声造影性能，和小动物体内成像显示PGd@tNBs颗粒主要通过呼吸和尿液代谢排出。压电显微镜表征强调了PGd@tNBs颗粒的出色压电性能。在靶向结合HER2-BC后，超声刺激影响细胞膜电位，导致可逆电穿孔。这个,反过来,影响细胞内外钙离子的平衡和线粒体膜电位。在被细胞摄取后，PGd@tNB,当暴露于超声波时，触发了活性氧（ROS）的产生，导致谷胱甘肽和超氧化物歧化酶的消耗，并实现声动力治疗。值得注意的是,重复超声刺激，PGd@tNBs颗粒结合并进入细胞后，增加ROS的产生并将凋亡率提高约45％。
结论：结论：开发的PGd@tNBs颗粒表现出出色的成像和治疗效果，具有精确诊断和个性化治疗HER2BC的潜力。
