Polymer Program, Institute of Materials Sciences , University of Connecticut , 191 Auditorium Road , Storrs , Connecticut 06269 , United States.
Department of Chemistry , National Chung Hsing University , Taichung 402 , Taiwan , ROC.
ACS Appl Mater Interfaces. 2019 Mar 20;11(11):10505-10519. doi: 10.1021/acsami.8b21609. Epub 2019 Mar 11.
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.
纳米载体输送系统的物理和生化特性的组合调制是纳米医学领域的一个新兴课题。在这里，我们研究了将主动靶向部分纳入纳米载体及其形态对纳米医学癌症治疗的增强渗透和保留效应的联合影响。我们合成、表征了具有低多分散性、亚 50nm 尺寸范围和相同化学组成的自组装脂质盘状和囊泡状纳米粒子，并将其与体外癌症细胞内化、体内肿瘤积累和癌症治疗进行了相关研究。事实上，叶酸偶联双锥形脂质体的效果最好，这表明盘状载体优于球形载体，并且由于靶向配体/受体结合提高了靶向效率。该方法成功地被应用于设计用于光动力治疗的纳米载体，其在体外和体内疗效上呈现出一致的趋势：叶酸纳米盘＞叶酸囊泡＞非叶酸纳米盘＞非叶酸囊泡。叶酸盘不仅表现出更高的肿瘤摄取和光热治疗效率，而且还最小化了皮肤光敏副作用。纳米双锥形脂质体作为纳米载体的优势，包括尺寸明确、形成稳定、易于包封疏水分子（治疗剂和/或诊断剂）、易于掺入靶向分子以及低毒性，使通用的体内多模态递药平台的规模化制造成为可能。
