近红外荧光阿霉素-共轭聚（乙二醇）双磷酸纳米颗粒的靶向药物递送用于小鼠模型中原发性和转移性骨癌症的诊断和治疗
标题：近红外荧光阿霉素-共轭聚（乙二醇）双磷酸纳米颗粒的靶向药物递送用于小鼠模型中原发性和转移性骨癌症的诊断和治疗
Targeted Drug Delivery of Near IR Fluorescent Doxorubicin-Conjugated Poly(ethylene glycol) Bisphosphonate Nanoparticles for Diagnosis and Therapy of Primary and Metastatic Bone Cancer in a Mouse Model
作者：S. Rudnick-Glick, E. Corem-Salkmon, I. Grinberg, S. Margel
链接：[https://jnanobiotechnology.biomedcentral.com/articles/10.1186/s12951-016-0233-6](https://jnanobiotechnology.biomedcentral.com/articles/10.1186/s12951-016-0233-6)
摘要：
本研究开发了一种将DOX通过NHS-PEG-NHS偶联剂连接至含双膦酸盐的PEG纳米粒子上，形成的靶向骨癌的药物递送系统。该纳米粒子在生理pH下表现出高稳定性，负电位约为−40 mV。与游离DOX相比，该系统在较低浓度下即可实现更高的细胞摄取和治疗效果，显示出良好的靶向性和治疗潜力。
Most primary and metastatic bone tumors demonstrate increased osteoclast activity and bone resorption. Current treatment is based on a combination of surgery, radiotherapy and chemotherapy. Severe side effects are associated with chemotherapy due to use of high dosage and nonspecific uptake. Bisphosphonates have a strong affinity to Ca2+ ions and are widely used in the treatment of bone disorders.
结论：
DOX-PEG-NHS修饰的双膦酸盐纳米粒子在骨癌治疗中显示出优良的靶向性和疗效，具有潜在的临床应用前景。
We have engineered a unique biodegradable bisphosphonate nanoparticle (NPs) bearing two functional surface groups: (1) primary amine groups for covalent attachment of a dye/drug (e.g. NIR dye Cy 7 or doxorubicin); (2) bisphosphonate groups for targeting and chelation to bone hydroxyapatite. In addition, these engineered NPs contain high polyethyleneglycol (PEG) concentration in order to increase their blood half life time. In vitro experiments on Saos-2 human osteosarcoma cell line, demonstrated that at a tenth of the concentration, doxorubicin-conjugated bisphosphonate NPs achieved a similar uptake to free doxorubicin. In vivo targeting experiments using the NIR fluorescence bisphosphonate NPs on both Soas-2 human osteosarcoma xenograft mouse model and orthotopic bone metastases mCherry-labeled 4T1 breast cancer mouse model confirmed specific targeting. In addition, therapeutic in vivo experiments using doxorubicin-conjugated bisphosphonate NPs demonstrated a 40% greater inhibition of tumor growth in Saos-2 human osteosarcoma xenograft mouse model when compared to free doxorubicin.