Torchilin Vladimir P
Department of Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts 02115, USA.
Annu Rev Biomed Eng. 2006;8:343-75. doi: 10.1146/annurev.bioeng.8.061505.095735.
Intracellular delivery of various drugs, including DNA, and drug carriers can sharply increase the efficiency of various treatment protocols. However, the receptor-mediated endocytosis of drugs, drug carriers, and DNA results in their lysosomal delivery and significant degradation. The problem can be solved and therapy efficacy still further increased if the approaches for direct intracytoplasmic delivery that bypass the endocytic pathway are developed. This is especially important for many anticancer drugs (proapoptotic drugs whose primary action site is the mitochondrial membrane) and gene therapy (nuclear or mitochondrial genomes should be targeted). This review considers several current approaches for intracellular drug delivery: the use of pH-sensitive liposomes, the use of cell-penetrating proteins and peptides, and the use of immunoliposomes targeting intracellular antigens. Among intracellular targets, nuclei (gene therapy), mitochondria (proapoptotic cancer therapy and targeting of the mitochondrial genome), and lysosomes (lysosomal targeting of enzymes for the therapy of the lysosomal storage diseases) are considered. Examples of successful intracellular and organelle-specific delivery of biologically active molecules, including DNA, are presented; unanswered questions, challenges, and future trends are also discussed.
包括DNA在内的各种药物以及药物载体的细胞内递送可大幅提高各种治疗方案的效率。然而，药物、药物载体和DNA的受体介导内吞作用会导致它们被递送至溶酶体并发生显著降解。如果开发出绕过内吞途径的直接胞质内递送方法，这个问题就能得到解决，治疗效果还能进一步提高。这对于许多抗癌药物（主要作用位点是线粒体膜的促凋亡药物）和基因治疗（应靶向细胞核或线粒体基因组）尤为重要。本文综述了几种当前的细胞内药物递送方法：使用pH敏感脂质体、使用细胞穿透蛋白和肽以及使用靶向细胞内抗原的免疫脂质体。在细胞内靶点中，讨论了细胞核（基因治疗）、线粒体（促凋亡癌症治疗和线粒体基因组靶向）和溶酶体（用于溶酶体贮积病治疗的酶的溶酶体靶向）。文中给出了包括DNA在内的生物活性分子成功进行细胞内和细胞器特异性递送的实例；还讨论了未解决的问题、挑战和未来趋势。
