†State Key Laboratory of Chemical Engineering and Center for Bionanoengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China.
§Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland 21218, United States.
ACS Nano. 2015 Jul 28;9(7):7195-206. doi: 10.1021/acsnano.5b02017. Epub 2015 Jul 15.
The specific sizes that determine optimal nanoparticle tumor accumulation, penetration, and treatment remain inconclusive because many studies compared nanoparticles with multiple physicochemical variables (e.g., chemical structures, shapes, and other physical properties) in addition to the size. In this study, we synthesized amphiphilic block copolymers of 7-ethyl-10-hydroxylcamptothecin (SN38) prodrug and fabricated micelles with sizes ranging from 20 to 300 nm from a single copolymer. The as-prepared micelles had exactly the same chemical structures and similar physical properties except for size, which provided an ideal platform for a systematic investigation of the size effects in cancer drug delivery. We found that the micelle's blood circulation time and tumor accumulation increased with the increase in their diameters, with optimal diameter range of 100 to 160 nm. However, the much higher tumor accumulation of the large micelles (100 nm) did not result in significantly improved therapeutic efficacy, because the large micelles had poorer tumor penetration than the small ones (30 nm). An optimal size that balances drug accumulation and penetration in tumors is critical for improving the therapeutic efficacy of nanoparticulate drugs.
确定最佳纳米颗粒肿瘤积累、穿透和治疗所需的具体尺寸仍然不确定，因为许多研究除了尺寸之外，还将纳米颗粒与多种物理化学变量（例如化学结构、形状和其他物理性质）进行了比较。在这项研究中，我们合成了喜树碱（SN38）前药的两亲嵌段共聚物，并从单一共聚物中制备了尺寸在 20 至 300nm 之间的胶束。所制备的胶束具有完全相同的化学结构和相似的物理性质，除了尺寸外，这为系统研究癌症药物传递中的尺寸效应提供了理想的平台。我们发现，胶束的血液循环时间和肿瘤积累随其直径的增加而增加，最佳直径范围为 100 至 160nm。然而，大胶束（100nm）的肿瘤积累增加并没有导致治疗效果的显著改善，因为大胶束的肿瘤穿透性比小胶束（30nm）差。平衡肿瘤内药物积累和穿透的最佳尺寸对于提高纳米颗粒药物的治疗效果至关重要。
