Nanomedicine Laboratory, Centre for Drug Delivery Research, The School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom.
Acc Chem Res. 2011 Oct 18;44(10):1094-104. doi: 10.1021/ar200105p. Epub 2011 Aug 3.
For decades, clinicians have used liposomes, self-assembled lipid vesicles, as nanoscale systems to deliver encapsulated anthracycline molecules for cancer treatment. The more recent proposition to combine liposomes with nanoparticles remains at the preclinical development stages; however, such hybrid constructs present great opportunities to engineer theranostic nanoscale delivery systems, which can combine simultaneous therapeutic and imaging functions. Many novel nanoparticles of varying chemical compositions are being developed in nanotechnology laboratories, but further chemical modification is often required to make these structures compatible with the biological milieu in vitro and in vivo. Such nanoparticles have shown promise as diagnostic and therapeutic tools and generally offer a large surface area that allows covalent and non-covalent surface functionalization with hydrophilic polymers, therapeutic moieties, and targeting ligands. In most cases, such surface manipulation diminishes the theranostic properties of nanoparticles and makes them less stable. From our perspective, liposomes offer structural features that can make nanoparticles biocompatible and present a clinically proven, versatile platform for further enhancement of the pharmacological and diagnostic efficacy of nanoparticles. In this Account, we describe two examples of liposome-nanoparticle hybrids developed as theranostics: liposome-quantum dot hybrids loaded with a cytotoxic drug (doxorubicin) and artificially enveloped adenoviruses. We incorporated quantum dots into lipid bilayers, which rendered them dispersible in physiological conditions. This overall vesicular structure allowed them to be loaded with doxorubicin molecules. These structures exhibited cytotoxic activity and labeled cells both in vitro and in vivo. In an alternative design, lipid bilayers assembled around non-enveloped viral nanoparticles and altered their infection tropism in vitro and in vivo with no chemical or genetic capsid modifications. Overall, we have attempted to illustrate how alternative strategies to incorporate nanoparticles into liposomal nanostructures can overcome some of the shortcomings of nanoparticles. Such hybrid structures could offer diagnostic and therapeutic combinations suitable for biomedical and even clinical applications.
几十年来，临床医生一直将脂质体（自组装的脂质囊泡）用作纳米级系统，以递送封装的蒽环类药物分子用于癌症治疗。将脂质体与纳米颗粒结合的这一更为近期的提议仍处于临床前开发阶段；然而，这种混合结构为构建治疗诊断学纳米级递药系统提供了极好的机会，该系统可将同时的治疗和成像功能结合在一起。许多不同化学成分的新型纳米颗粒正在纳米技术实验室中得到开发，但通常需要进一步的化学修饰，以使这些结构与体外和体内的生物环境兼容。这些纳米颗粒已显示出作为诊断和治疗工具的潜力，通常具有较大的表面积，允许与亲水性聚合物、治疗部分和靶向配体进行共价和非共价的表面功能化。在大多数情况下，这种表面操作会降低纳米颗粒的治疗诊断性能，并使它们不太稳定。从我们的角度来看，脂质体提供了结构特征，可以使纳米颗粒具有生物相容性，并为进一步增强纳米颗粒的药理和诊断功效提供了经过临床验证的多功能平台。在本述评中，我们描述了两种作为治疗诊断学而开发的脂质体-纳米颗粒杂化物的实例：载有细胞毒性药物（阿霉素）的脂质体-量子点杂化物和人工包裹的腺病毒。我们将量子点掺入脂质双层中，使其在生理条件下具有分散性。这种整体囊泡结构使它们能够装载阿霉素分子。这些结构在体外和体内均表现出细胞毒性，并对细胞进行标记。在另一种设计中，脂质双层围绕非包膜病毒纳米颗粒组装，并在不进行化学或遗传衣壳修饰的情况下改变其在体外和体内的感染趋向性。总体而言，我们试图说明将纳米颗粒纳入脂质体纳米结构的替代策略如何克服纳米颗粒的某些缺点。这种混合结构可提供适合生物医学甚至临床应用的诊断和治疗组合。
