姜黄素脂质聚合物杂化纳米颗粒的构建及表征

Construction and Characterization of the Curcumin Loaded Lipid-polymer Hybrid Nanoparticles

姜黄素存在的水溶性差、稳定性差及生物利用度低等缺陷限制了其在抗肿瘤领域的临床应用。基于肿瘤组织的弱酸性环境和肿瘤细胞内的还原性环境,设计并合成了一种兼具还原敏感性和电荷反转性能的两亲性聚合物。由该聚合物、磷脂和聚己内酯(PCL)通过自组装方式构建的脂质聚合物杂化纳米颗粒(LPNPs),具有良好的均一性和适宜的粒径尺寸,能够有效负载抗肿瘤药物姜黄素(载药率:6.78%,包封率:92.3%)。在正常的生理条件下(pH值7.4)纳米颗粒表面呈负电性,有助于降低蛋白非特异性吸附,提高其血液相容性。而在弱酸性环境中(pH值6.5),其表面则可以转化为正电性,增强其进入肿瘤细胞的能力。在模拟的还原性条件下纳米颗粒的粒径尺寸和粒径分布能够发生显著性变化,表明其具有良好的还原敏感性,有望在肿瘤细胞内实现微环境响应性释药。本研究所制备的智能纳米载体为实现抗肿瘤药物的高效递送和可控释药提供了一种新的思路。

The clinical application of curcumin in the field of cancer therapy has been hindered by the problems such as poor water solubility,poor stability and low bioavailability.Based on the the weakly acidic environment of tumor tissue and the reductive environment of tumor cells,an amphiphilic polymer with both reduction sensitivity and charge reversal properties was designed and synthesized.Then the lipid-polymer hybrid nanoparticles(LPNPs)with good uniformity and appropriate particle size were prepared by the self-assembly of this amphiphilic polymer,phosphatide and polycaprolactone(PCL),which could effectively load the anti-tumor drug curcumin with a high drug loading content(DLC:6.78%)and entrapment efficiency(EE:92.3%).The nanoparticles are negatively charged under normal conditions,which ensures the low adsorption of protein in the blood and excellent hemocompatibility.In a weakly acidic environment(pH value 6.5),the surface charge of the nanopariticles convert to positive,facilitating the uptake of the nanoparticles by cancer cells.There are significant changes in the particle size and particle size distribution of nanoparticles under the simulated reducing conditions,indicating the good reduction sensitivity of the nanoparticles,which guarantees the triggered drug release in response to tumor microenvironment.The intelligent nanocarrier reported in this paper provides a new method for the efficient delivery and controlled release of anti-tumor drugs.