Department of Chemical and Biological Engineering, University of Colorado, 3415 Colorado Ave, Boulder, CO, 80303, USA.
Materials Science and Engineering Program, University of Colorado, 3415 Colorado Ave, Boulder, CO, 80303, USA.
Adv Mater. 2017 Jun;29(24). doi: 10.1002/adma.201700743. Epub 2017 Apr 11.
Co-delivery of both chemotherapy drugs and siRNA from a single delivery vehicle can have a significant impact on cancer therapy due to the potential for overcoming issues such as drug resistance. However, the inherent chemical differences between charged nucleic acids and hydrophobic drugs have hindered entrapment of both components within a single carrier. While poly(ethylene glycol)-block-poly(lactic-co-glycolic acid) (PEG-PLGA) copolymers have been used successfully for targeted delivery of chemotherapy drugs, loading of DNA or RNA has been poor. It is demonstrated that significant amounts of DNA can be encapsulated within PLGA-containing nanoparticles through the use of a new synthetic DNA analog, click nucleic acids (CNAs). First, triblock copolymers of PEG-CNA-PLGA are synthesized and then formulated into polymer nanoparticles from oil-in-water emulsions. The CNA-containing particles show high encapsulation of DNA complementary to the CNA sequence, whereas PEG-PLGA alone shows minimal DNA loading, and non-complementary DNA strands do not get encapsulated within the PEG-CNA-PLGA nanoparticles. Furthermore, the dye pyrene can be successfully co-loaded with DNA and lastly, a complex, larger DNA sequence that contains an overhang complementary to the CNA can also be encapsulated, demonstrating the potential utility of the CNA-containing particles as carriers for chemotherapy agents and gene silencers.
由于克服耐药性等问题的潜力，从单一递药载体共递化疗药物和 siRNA 对癌症治疗会产生重大影响。然而，带电荷的核酸和疏水性药物之间固有的化学差异阻碍了这两种成分被包封在单一载体中。虽然聚（乙二醇）-嵌段-聚（乳酸-共-乙醇酸）（PEG-PLGA）共聚物已成功用于化疗药物的靶向递送，但 DNA 或 RNA 的负载能力较差。通过使用新型合成 DNA 类似物，点击核酸（CNA），证明可以将大量 DNA 封装在含有 PLGA 的纳米颗粒中。首先，合成了 PEG-CNA-PLGA 的三嵌段共聚物，然后从油包水乳液中将其配制成聚合物纳米颗粒。含 CNA 的颗粒对与 CNA 序列互补的 DNA 具有高的包封率，而单独的 PEG-PLGA 则显示出最小的 DNA 负载，并且非互补的 DNA 链不会被包封在 PEG-CNA-PLGA 纳米颗粒中。此外，可以成功地将染料芘与 DNA 共载，最后，可以封装含有与 CNA 互补的突出端的复杂的较大 DNA 序列，这表明含 CNA 的颗粒作为化疗药物和基因沉默剂载体具有潜在的用途。
