Bioinspired Nanoparticles Engineered for Enhanced Delivery to the Bone.
Bioinspired Nanoparticles Engineered for Enhanced Delivery to the Bone.
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DOI：
10.1021/acsanm.9b01226
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发表时间：
2019-10-25
影响因子：
5.9
通讯作者：
Ranjan AP
中科院分区：
文献类型：
--
作者：
Gdowski AS;Lampe JB;Lin VJT;Joshi R;Wang YC;Mukerjee A;Vishwanatha JK;Ranjan AP
尽管全身给药科学取得了进展，但将治疗剂靶向人体特定器官仍然是一个挑战。我们设计了一种可编程生物启发纳米颗粒(P-BiNP)递送系统，通过将聚合物纳米颗粒包裹在程序化癌细胞膜上，同时靶向骨骼并增加同型肿瘤细胞的摄取。这种方法的独特之处在于，我们结合了相关的临床生物信息学数据，以指导这些纳米颗粒被设计为模拟的生物过程的设计和增强。为了实现这一点，一项对转移性前列腺癌患者核糖核酸表达的分析发现，ITGB3(整合素αVβ3的一个亚单位)在骨转移患者中过度表达。癌细胞被刺激增加这种整合素在细胞表面的表达，这些膜随后被用来包裹携带聚合物纳米颗粒的货物。物理化学优化和表征表明，P-BiNPs在尺寸、ζ电位和稳定性方面都具有良好的品质。体外试验证实，癌细胞的同型结合和摄取增强。在小鼠模型中，P-BiNPs还显示了体内骨骼定位的改善。这种为双重同型和骨靶向确定临床相关靶点的新方法有可能成为影响骨骼的疾病的治疗和成像方式的一种战略，以及将纳米颗粒输送到其他感兴趣的器官的更广泛的影响。
Targeting therapeutic agents to specific organs in the body remains a challenge despite advances in the science of systemic drug delivery. We have engineered a programmable-bioinspired nanoparticle (P-BiNP) delivery system to simultaneously target the bone and increase uptake in homotypic tumor cells by coating polymeric nanoparticles with programmed cancer cell membranes. This approach is unique in that we have incorporated relevant clinical bioinformatics data to guide the design and enhancement of biological processes that these nanoparticles are engineered to mimic. To achieve this, an analysis of RNA expression from metastatic prostate cancer patients identified ITGB3 (a subunit of integrin αVβ3) as overexpressed in patients with bone metastasis. Cancer cells were stimulated to increase this integrin expression on the cell surface, and these membranes were subsequently used to coat cargo carrying polymeric nanoparticles. Physicochemical optimization and characterization of the P-BiNPs showed desirable qualities regarding size, ζ potential, and stability. In vitro testing confirmed enhanced homotypic binding and uptake in cancer cells. P-BiNPs also demonstrated improved bone localization in vivo with a murine model. This novel approach of identifying clinically relevant targets for dual homotypic and bone targeting has potential as a strategy for treatment and imaging modalities in diseases that affect the bone as well as broader implications for delivering nanoparticles to other organs of interest.
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DOI：
10.1016/j.jconrel.2015.07.019
发表时间：
2015-12-28
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Luk BT;Zhang L
通讯作者：
Zhang L
影响因子：
46.2
作者：
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通讯作者：
Mahmoudi M
DOI：
10.1073/pnas.1106634108
发表时间：
2011-07-05
影响因子：
11.1
作者：
Hu, Che-Ming J.;Zhang, Li;Zhang, Liangfang
通讯作者：
Zhang, Liangfang
影响因子：
6.7
作者：
Luk BT;Hu CM;Fang RH;Dehaini D;Carpenter C;Gao W;Zhang L
通讯作者：
Zhang L
DOI：
10.1615/critrevtherdrugcarriersyst.2013006475
发表时间：
2013
影响因子：
2.7
作者：
Hines DJ;Kaplan DL
通讯作者：
Kaplan DL