Jhaveri Aditi, Torchilin Vladimir
a 1 Northeastern University, Center for Pharmaceutical Biotechnology and Nanomedicine, Department of Pharmaceutical Sciences , Boston, MA 02115, USA.
b 2 Northeastern University, Center for Pharmaceutical Biotechnology and Nanomedicine, Department of Pharmaceutical Sciences , Boston, MA 02115, USA
Expert Opin Drug Deliv. 2016;13(1):49-70. doi: 10.1517/17425247.2015.1086745. Epub 2015 Sep 11.
Recent trends in drug delivery indicate a steady increase in the use of targeted therapeutics to enhance the specific delivery of biologically active payloads to diseased tissues while avoiding their off-target effects. However, in most cases, the distribution of therapeutics inside cells and their targeting to intracellular targets still presents a formidable challenge. The main barrier to intracellular delivery is the translocation of therapeutic molecules across the cell membrane, and ultimately through the membrane of their intracellular target organelles. Another prerequisite for an efficient intracellular localization of active molecules is their escape from the endocytic pathway.
Pharmaceutical nanocarriers have demonstrated substantial advantages for the delivery of therapeutics and offer elegant platforms for intracellular delivery. They can be engineered with both intracellular and organelle-specific targeting moieties to deliver encapsulated or conjugated cargoes to specific sub-cellular targets. In this review, we discuss important aspects of intracellular drug targeting and delivery with a focus on nanocarriers modified with various ligands to specifically target intracellular organelles.
Intracellular delivery affords selective localization of molecules to their target site, thus maximizing their efficacy and safety. The advent of novel nanocarriers and targeting ligands as well as exploration of alternate routes for the intracellular delivery and targeting has prompted extensive research, and promises an exciting future for this field.
药物递送的最新趋势表明，靶向治疗药物的使用稳步增加，以增强生物活性药物向患病组织的特异性递送，同时避免其脱靶效应。然而，在大多数情况下，治疗药物在细胞内的分布及其对细胞内靶点的靶向作用仍然是一项艰巨的挑战。细胞内递送的主要障碍是治疗分子穿过细胞膜，并最终穿过其细胞内靶细胞器的膜。活性分子在细胞内有效定位的另一个先决条件是它们从内吞途径中逃逸。
药物纳米载体已证明在治疗药物递送方面具有显著优势，并为细胞内递送提供了优良的平台。它们可以通过细胞内和细胞器特异性靶向部分进行工程设计，以将封装或偶联的货物递送至特定的亚细胞靶点。在本综述中，我们讨论细胞内药物靶向和递送的重要方面，重点关注用各种配体修饰以特异性靶向细胞内细胞器的纳米载体。
细胞内递送使分子能够选择性地定位于其靶位点，从而最大限度地提高其疗效和安全性。新型纳米载体和靶向配体的出现，以及对细胞内递送和靶向的替代途径的探索，促使了广泛的研究，并为该领域带来了令人兴奋的未来。
