Nanochemistry and Bioimaging Group, Laboratoire de Bioimagerie et Pathologies, UMR 7021 CNRS, Université de Strasbourg, 74 route du Rhin, 67401, Illkirch, France.
J Mater Chem B. 2019 Aug 28;7(34):5199-5210. doi: 10.1039/c8tb02781a.
Uncontrolled release of encapsulated drugs and contrast agents from biodegradable polymer nanoparticles (NPs) is a central problem in drug delivery and bioimaging. In particular, it concerns polymeric NPs prepared by nanoprecipitation, where this release (so-called burst release) can be very significant, leading to side effects and/or bioimaging artifacts. Here, we systematically studied the effect of the chemical structure of cargo molecules, BODIPY dye derivatives, on their capacity to be loaded into ∼50 nm PLGA NPs without leakage in biological media. Absorption and fluorescence spectroscopy suggested that all the dyes, except the most polar BODIPY derivative, formed blended structures with polymer NPs. Fluorescence correlation spectroscopy of dye-loaded NPs in the presence of serum proteins revealed that only the most hydrophobic BODIPY dyes, bearing one octadecyl chain or two octyl chains, remain inside the NPs, while all other derivatives are released into the serum medium. The time-lapse absorption and fluorescence studies confirmed this result, suggesting the release kinetics for the leaky NPs on the time scale of hours. Fluorescence microscopy of living cells incubated with BODIPY-loaded NPs showed that most of them exhibit strong dye leakage observed as a homogeneous distribution of fluorescence all over the cytoplasm. Importantly, NPs loaded with the most hydrophobic dyes exhibited high stability showing a dotted pattern in the perinuclear region, typical for endosomes and lysosomes. Our results highlight the significance of the cargo hydrophobicity for efficient encapsulation inside polymeric NPs prepared by nanoprecipitation, which enables designing stable cargo-loaded nanomaterials for bioimaging and drug delivery.
包封药物和对比剂从可生物降解聚合物纳米粒子（NPs）的失控释放是药物输送和生物成像的一个核心问题。特别是，通过纳米沉淀制备的聚合物 NPs 存在这种释放（所谓的突释），可能非常显著，导致副作用和/或生物成像伪影。在这里，我们系统地研究了货物分子（BODIPY 染料衍生物）的化学结构对其在生物介质中无泄漏地装载到约 50nmPLGA NPs 中的能力的影响。吸收和荧光光谱表明，除了最极性的 BODIPY 衍生物外，所有染料都与聚合物 NPs 形成混合结构。在存在血清蛋白的情况下，负载染料的 NPs 的荧光相关光谱研究表明，只有最疏水的 BODIPY 染料，带有一个十八烷基链或两个辛基链，仍留在 NPs 内部，而所有其他衍生物都释放到血清介质中。时移吸收和荧光研究证实了这一结果，表明在数小时的时间尺度上，漏出 NPs 的释放动力学。用负载 BODIPY 的 NPs 孵育的活细胞的荧光显微镜显示，它们中的大多数都表现出强烈的染料泄漏，表现为整个细胞质中荧光的均匀分布。重要的是，负载最疏水染料的 NPs 表现出高稳定性，在核周区域呈现点状图案，这是内体和溶酶体的典型特征。我们的结果强调了货物疏水性对于通过纳米沉淀制备的聚合物 NPs 内有效封装的重要性，这使得设计用于生物成像和药物输送的稳定载药纳米材料成为可能。
