Combinational Effects of Active Targeting, Shape, and Enhanced Permeability and Retention for Cancer Theranostic Nanocarriers
Combinational Effects of Active Targeting, Shape, and Enhanced Permeability and Retention for Cancer Theranostic Nanocarriers
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DOI：
10.1021/acsami.8b21609
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发表时间：
2019-03-20
影响因子：
9.5
通讯作者：
Nieh, Mu-Ping
中科院分区：
文献类型：
--
作者：
Rad, Armin Tahmasbi;Chen, Ching-Wen;Nieh, Mu-Ping
纳米载体传递系统的物理和生化特性的组合调节是纳米医学领域的一个新兴课题。在这里，我们研究了将活性靶向部分掺入纳米载体及其形态学的组合效应，其影响纳米药物癌症治疗的增强渗透和保留效应。自组装脂质盘状和囊泡纳米粒子与低多分散性的子-50 nm的尺寸范围和相同的化学组成的合成，表征，并与体外癌细胞内化，体内肿瘤积累和癌症治疗。叶酸相关的双胞产生最佳结果的事实表明盘状载体优于球形载体，并且由于靶向配体/受体结合而提高了靶向功效。该方法被成功地用于设计用于光动力疗法的纳米载体，其在体外和体内功效方面产生一致的趋势：叶酸纳米盘>叶酸囊泡>非叶酸纳米盘>非叶酸囊泡。叶酸片不仅具有较高的肿瘤吸收率和光热治疗效率，而且还能最大限度地减少皮肤光敏性副作用。作为纳米载体的纳米盘状双胞的优点，包括良好限定的尺寸、稳健的形成、疏水性分子（治疗和/或诊断）的容易包封、靶向分子的容易掺入和低毒性，使得能够可规模化地制造通用的体内多模式递送平台。
Combinatory modulation of the physical and biochemical characteristics of nanocarrier delivery systems is an emergent topic in the field of nanomedicine. Here, we studied the combined effects of incorporation of active targeting moieties into nanocarriers and their morphology affecting the enhanced permeation and retention effect for nanomedicine cancer therapy. Self-assembled lipid discoidal and vesicular nanoparticles with low-polydispersity sub-50 nm size range and identical chemical compositions were synthesized, characterized, and correlated with in vitro cancer cellular internalization, in vivo tumor accumulation and cancer treatments. The fact that folate-associated bicelle yields the best outcome is indicative of the preference for discoidal carriers over spherical carriers and the improved targeting efficacy due to the targeting ligand/receptor binding. The approach is successfully adopted to design the nanocarriers for photodynamic therapy, which yields a consistent trend in in vitro and in vivo efficacy: folate nanodiscs > folate vesicles > nonfolate nanodiscs > nonfolate vesicles. Folate discs not only have shown a higher tumor uptake and photothermal therapeutic efficiency, but also minimize skin photosensitivity side effects. The advantages of nanodiscoidal bicelles as nanocarriers, including well-defined size, robust formation, easy encapsulation of hydrophobic molecules (therapeutics and/or diagnostics), easy incorporation of targeting molecules, and low toxicity, enable the scalable manufacturing of a generalized in vivo multimodal delivery platform.