ACS Biomater Sci Eng. 2020 Jan 13;6(1):474-484. doi: 10.1021/acsbiomaterials.9b01587. Epub 2019 Dec 3.
The strategy of co-loading therapeutic agents in a single nanocarrier is the most common method in theranostic cancer research. However, it is still challenging to encapsulate theranostic agents that have different physicochemical properties in a single nanocarrier system because of the immiscibility between the hydrophobic fluorescent molecule and the hydrophilic drug molecule. Thus, we report a novel concept of a theranostic nanoparticle (NP) consisting of an amphiphilic near-infrared (NIR) dye as a hydrophilic drug delivery carrier with enhanced NIR imaging capability. Unlike conventional nanocarrier systems, the newly designed amphiphilic NIR dyes (Cy-C dyes) function as both the drug delivery carrier and the fluorescent imaging agent. It can be utilized for therapy and diagnosis simultaneously by simply encapsulating the hydrophilic drug. This method is innovative not only due to formation of the theranostic nanoparticle for immiscible hydrophilic drug delivery but also because of generation of strong fluorescence signals due to the Cy-C dyes on the surfaces of the NPs. In this study, Cy-C (C = C3, C6, and C9) dyes were designed by conjugating the heptamethine cyanine dye with poly(ethylene glycol) (PEG) and polyethyleneimine 2000 (PEI). The result was self-assembled structures that effectively encapsulated a hydrophilic drug molecule (MTX) without self-quenching and scattered light interference. Among the Cy-C NPs encapsulating MTX (Cy-C/MTX NPs), Cy-C6/MTX and Cy-C9/MTX formed a concentric supramolecular bilayer (like liposomes in aqueous solution) and were capable of translocating hydrophilic drug molecules to their aqueous interior spaces. The supramolecular bilayer structure of Cy-C9/MTX provides better particle stability and drug delivery efficacy than does the supramolecular monolayer structure of Cy-C3/MTX. In addition, Cy-C9/MTX demonstrated excellent blood circulation and long-term tumor retention qualities in living mice. The effective tumor suppression ability of Cy-C9/MTX validated the concept that the amphiphilic Cy-C9 dye is the best nanoplatform for theranostics based on hydrophilic drug delivery.
在单纳米载体中共同装载治疗剂的策略是治疗癌症研究中最常见的方法。然而，由于疏水性荧光分子和亲水性药物分子之间的不混溶性，将具有不同物理化学性质的治疗剂封装在单纳米载体系统中仍然具有挑战性。因此，我们报告了一种由两亲性近红外（NIR）染料组成的治疗诊断纳米粒子（NP）的新概念，该染料作为亲水性药物递送载体具有增强的 NIR 成像能力。与传统的纳米载体系统不同，新设计的两亲性 NIR 染料（Cy-C 染料）既可以作为药物递送载体，也可以作为荧光成像剂。通过简单地封装亲水性药物，它可以同时用于治疗和诊断。这种方法不仅新颖，因为形成了用于不相容的亲水性药物递送的治疗诊断纳米粒子，而且还因为 NPs 表面上的 Cy-C 染料产生了强荧光信号。在这项研究中，通过将七甲川花菁染料与聚乙二醇（PEG）和聚乙烯亚胺 2000（PEI）偶联，设计了 Cy-C（C = C3、C6 和 C9）染料。结果是自组装结构，有效地封装了亲水性药物分子（MTX），而没有自猝灭和散射光干扰。在封装 MTX 的 Cy-C NPs（Cy-C/MTX NPs）中，Cy-C6/MTX 和 Cy-C9/MTX 形成同心超分子双层（类似于水溶液中的脂质体），并能够将亲水性药物分子转移到其水相内部空间。Cy-C9/MTX 的超分子双层结构比 Cy-C3/MTX 的超分子单层结构提供更好的颗粒稳定性和药物递送功效。此外，Cy-C9/MTX 在活小鼠中表现出优异的血液循环和长期肿瘤保留特性。Cy-C9/MTX 的有效肿瘤抑制能力验证了基于亲水性药物递送的两亲性 Cy-C9 染料是治疗诊断的最佳纳米平台的概念。
