MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China.
Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, China.
ACS Appl Mater Interfaces. 2021 Apr 28;13(16):19387-19397. doi: 10.1021/acsami.1c04648. Epub 2021 Apr 20.
Poly(ethylene glycol) (PEG) is applied extensively in biomedical fields because of its nontoxic, nonimmunogenic, and protein resistance properties. However, the strong hydrophilicity of PEG prevents it from self-assembling into an amphiphilic micelle in water, making it a challenge to fabricate a full-PEG carrier to deliver hydrophobic anticancer drugs. Herein, a paclitaxel (PTX)-loaded nanodrug was readily prepared through self-assembly of PTX and an amphiphilic PEG derivative, which was synthesized via melt polycondensation of two PEG diols (i.e., PEG and PEG) and mercaptosuccinic acid. The full PEG component endows the nanocarrier with good biocompatibility. Furthermore, because of the core cross-linked structure via the oxidation of mercapto groups, the nanodrug can be selectively disassociated under an intratumor reductive microenvironment through the reduction of disulfide bonds to release the loaded PTX and kill the cancer cells while maintaining high stability under the extratumor physiological condition. Additionally, it was confirmed that the nanodrug not only prolongs the biocirculation time of PTX but also possesses excellent in vivo antitumor efficacy while avoiding side effects of free PTX, for example, liver damage, which is promising for delivering clinical hydrophobic drugs to treat a variety of malignant tumors.
聚乙二醇（PEG）由于其无毒、无免疫原性和抗蛋白质特性，被广泛应用于生物医学领域。然而，PEG 的强亲水性阻止其在水中自组装成两亲性胶束，这使得制备全 PEG 载体来递送疏水性抗癌药物具有挑战性。在此，通过 PTX 和两亲性 PEG 衍生物的自组装，容易地制备了负载 PTX 的纳米药物，该衍生物通过两个 PEG 二醇（即 PEG 和 PEG）和巯基琥珀酸的熔融缩聚合成。全 PEG 组分赋予纳米载体良好的生物相容性。此外，由于通过巯基氧化形成的核交联结构，纳米药物可以通过还原二硫键在肿瘤内还原微环境中选择性解离，释放负载的 PTX 并杀死癌细胞，同时在肿瘤外生理条件下保持高稳定性。此外，证实该纳米药物不仅延长了 PTX 的生物循环时间，而且具有优异的体内抗肿瘤功效，同时避免了游离 PTX 的副作用，例如肝损伤，有望用于输送临床疏水性药物来治疗各种恶性肿瘤。
