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Dual-Targeting Heparin-Based Nanoparticles that Re-Assemble in Blood for Glioma Therapy through Both Anti-Proliferation and Anti-Angiogenesis

机译：基于抗肝素和抗血管生成的胶质瘤疗法在血液中重新组装的基于双靶肝素的纳米颗粒。

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摘要

The efficient and specific delivery of nanoparticles (NPs) to brain tumors is crucial for successful glioma treatment. Heparin-based polymers decorated with two peptides self-assemble into multi-functional NPs that specifically target glioma cells. These NPs re-self-assemble to a smaller size in blood, which is beneficial for in-vivo brain drug delivery. The hydrodynamic size of one type of these NPs is 63 +/- 11 nm under blood-mimic conditions (10% fetal bovine serum), but it is 164 +/- 16 nm in water. Additionally their zeta potential is more neutral in the blood-mimic conditions. Transmission electron microscopy reveals the morphology of the spherical NPs. In vitro experiments demonstrate that the NPs exhibit a high cellular uptake and the ability to efficiently discourage proliferation, endothelial-lined vessels, and vasculogenic mimicry. In vivo studies demonstrate that the NPs can by-pass the normal blood-brain and blood-(brain tumor) barriers and specifically accumulate in glioma tissues; moreover, they present an excellent anti-glioma effect in subcutaneous/intracranial glioma-bearing mice. Their superiority is due to their appropriate size in blood and the synergic effect arising from their targeting of two different receptors. The data suggests that these NPs are ideal for anti-glioma therapy.
机译：纳米粒子（NPs）向脑肿瘤的有效和特异性传递对于成功治疗神经胶质瘤至关重要。用两种肽修饰的基于肝素的聚合物会自组装为特异性靶向神经胶质瘤细胞的多功能NP。这些NP在血液中重新自我组装成较小的尺寸，这对于体内脑内药物输送是有益的。在血液模拟条件下（10％胎牛血清），一种类型的这些NP的流体动力学大小为63 +/- 11 nm，但在水中为164 +/- 16 nm。另外，它们的ζ电位在血液模拟条件下更为中性。透射电子显微镜揭示了球形NP的形态。体外实验表明，NPs表现出较高的细胞摄取能力，并具有有效抑制增殖，内皮衬里的血管和血管生成拟态的能力。体内研究表明，NPs可以绕过正常的血脑屏障和血（脑肿瘤）屏障，并且特别是在神经胶质瘤组织中积累。此外，它们在皮下/颅内神经胶质瘤小鼠中表现出优异的抗神经胶质瘤作用。它们的优越性是由于它们在血液中的大小合适，以及由于它们靶向两种不同的受体而产生的协同作用。数据表明这些NP对于抗神经胶质瘤治疗是理想的。

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  • 来源
    《Advanced Functional Materials》 |2016年第43期|7873-7885|共13页
  • 作者

    Wang Jihui; Yang Yuantao; Zhang Yonghong; Huang Min; Zhou Zhenjun; Luo Wanxian; Tang Jiao; Wang Jianguo; Xiao Qian; Chen Huajian; Cai Yingqian; Sun Xinlin; Wang Ying; Ke Yiquan;

  • 作者单位

    Southern Med Univ, Sch Basic Med Sci, Canc Res Inst, Guangdong Prov Key Lab Canc Immunotherapy Res, Guangzhou 510515, Guangdong, Peoples R China;

    Southern Med Univ, Minist China,Dept Neurosurg,Zhujiang Hosp, Guangdong Prov Key Lab Brain Funct Repair & Regen, Natl Key Clin Specialty,Engn Technol Res Ctr Educ, Guangzhou 510282, Guangdong, Peoples R China;

    Southern Med Univ, Minist China,Dept Neurosurg,Zhujiang Hosp, Guangdong Prov Key Lab Brain Funct Repair & Regen, Natl Key Clin Specialty,Engn Technol Res Ctr Educ, Guangzhou 510282, Guangdong, Peoples R China;

    Southern Med Univ, Minist China,Dept Neurosurg,Zhujiang Hosp, Guangdong Prov Key Lab Brain Funct Repair & Regen, Natl Key Clin Specialty,Engn Technol Res Ctr Educ, Guangzhou 510282, Guangdong, Peoples R China;

    Southern Med Univ, Minist China,Dept Neurosurg,Zhujiang Hosp, Guangdong Prov Key Lab Brain Funct Repair & Regen, Natl Key Clin Specialty,Engn Technol Res Ctr Educ, Guangzhou 510282, Guangdong, Peoples R China;

    Southern Med Univ, Sch Basic Med Sci, Canc Res Inst, Guangdong Prov Key Lab Canc Immunotherapy Res, Guangzhou 510515, Guangdong, Peoples R China;

    Southern Med Univ, Sch Basic Med Sci, Canc Res Inst, Guangdong Prov Key Lab Canc Immunotherapy Res, Guangzhou 510515, Guangdong, Peoples R China;

    Southern Med Univ, Sch Basic Med Sci, Canc Res Inst, Guangdong Prov Key Lab Canc Immunotherapy Res, Guangzhou 510515, Guangdong, Peoples R China;

    Southern Med Univ, Sch Basic Med Sci, Canc Res Inst, Guangdong Prov Key Lab Canc Immunotherapy Res, Guangzhou 510515, Guangdong, Peoples R China;

    Southern Med Univ, Minist China,Dept Neurosurg,Zhujiang Hosp, Guangdong Prov Key Lab Brain Funct Repair & Regen, Natl Key Clin Specialty,Engn Technol Res Ctr Educ, Guangzhou 510282, Guangdong, Peoples R China;

    Southern Med Univ, Minist China,Dept Neurosurg,Zhujiang Hosp, Guangdong Prov Key Lab Brain Funct Repair & Regen, Natl Key Clin Specialty,Engn Technol Res Ctr Educ, Guangzhou 510282, Guangdong, Peoples R China;

    Southern Med Univ, Minist China,Dept Neurosurg,Zhujiang Hosp, Guangdong Prov Key Lab Brain Funct Repair & Regen, Natl Key Clin Specialty,Engn Technol Res Ctr Educ, Guangzhou 510282, Guangdong, Peoples R China;

    Southern Med Univ, Sch Basic Med Sci, Canc Res Inst, Guangdong Prov Key Lab Canc Immunotherapy Res, Guangzhou 510515, Guangdong, Peoples R China;

    Southern Med Univ, Minist China,Dept Neurosurg,Zhujiang Hosp, Guangdong Prov Key Lab Brain Funct Repair & Regen, Natl Key Clin Specialty,Engn Technol Res Ctr Educ, Guangzhou 510282, Guangdong, Peoples R China;

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