Active Targeting Significantly Outperforms Nanoparticle Size in Facilitating Tumor-Specific Uptake in Orthotopic Pancreatic Cancer.
Active Targeting Significantly Outperforms Nanoparticle Size in Facilitating Tumor-Specific Uptake in Orthotopic Pancreatic Cancer.
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DOI：
10.1021/acsami.1c09379
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发表时间：
2021-10-27
影响因子：
9.5
通讯作者：
McNally, Lacey R.
中科院分区：
文献类型：
--
作者：
MacCuaig, William M.;Fouts, Benjamin L.;McNally, Molly W.;Grizzle, William E.;Chuong, Phillip;Samykutty, Abhilash;Mukherjee, Priyabrata;Li, Min;Jasinski, Jacek B.;Behkam, Bahareh;McNally, Lacey R.
关键词：
纳米颗粒作为癌症的治疗诊断载体被广泛研究，然而，由于肿瘤特异性差，临床转化受到限制。最大化肿瘤摄取的特征仍然存在争议，特别是使用临床相关的原位模型。在此，我们报告了一项系统性研究，评估了两个主要特征对肿瘤特异性的影响，即，主动与被动靶向和纳米颗粒尺寸，以评估体内胰腺癌模型的相对影响。通过细胞内化和释放机制观察到，对于原位胰腺肿瘤的摄取，经由V7肽的主动靶向上级于被动靶向，而与纳米颗粒尺寸无关。然而，尺寸对主动靶向纳米颗粒的摄取具有次要影响。纳米颗粒大小对被动靶向纳米颗粒的摄取没有显著影响。结果突出了主动靶向在胰腺肿瘤摄取方面优于纳米颗粒尺寸。这些发现提出了一个框架，用于优化类似的非聚集体纳米颗粒，用于胰腺癌和胰腺癌的诊断和治疗。
Nanoparticles are widely studied as theranostic vehicles for cancer, however, clinical translation has been limited due to poor tumor-specificity. Features that maximize tumor uptake remain controversial, particularly using clinically relevant, orthotopic models. Herein, we report a systematic study that assesses two major features for impact on tumor specificity, i.e., active vs. passive targeting and nanoparticle size, to evaluate relative influences for a pancreatic cancer model, in vivo. Active targeting via V7 peptide is superior to passive targeting for uptake by orthotopic pancreatic tumors, irrespective of nanoparticle size, observed through cell internalization and release mechanisms. However, size has a secondary effect on uptake for actively-targeted nanoparticles. Nanoparticle size had no significant effect on uptake of passively-targeted nanoparticles. Results highlight the superiority of active targeting over nanoparticle size for pancreatic tumor uptake. These findings suggest a framework for optimizing similar non-aggregate nanoparticles for diagnostic and therapeutic treatment of pancreatic and recalcitrant cancers.
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DOI：
10.1016/j.jconrel.2013.09.013
发表时间：
2013-12-28
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Ernsting MJ;Murakami M;Roy A;Li SD
通讯作者：
Li SD
影响因子：
4
作者：
Andreev OA;Engelman DM;Reshetnyak YK
通讯作者：
Reshetnyak YK
影响因子：
5.4
作者：
Frickenstein AN;Hagood JM;Britten CN;Abbott BS;McNally MW;Vopat CA;Patterson EG;MacCuaig WM;Jain A;Walters KB;McNally LR
通讯作者：
McNally LR
影响因子：
0.7
作者：
Gachoka D
通讯作者：
Gachoka D
DOI：
10.4103/2230-973x.160844
发表时间：
2015-07
影响因子：
0.5
作者：
Bharti C;Nagaich U;Pal AK;Gulati N
通讯作者：
Gulati N