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Poly(L‐Glutamic Acid)‐Drug Conjugates for Chemo‐ and Photodynamic Combination Therapy
Macromolecular Bioscience ( IF 4.6 ) Pub Date : 2020-10-11 , DOI: 10.1002/mabi.202000192
Haiyang Yu 1, 2, 3 , Yanli Bao 1 , Caina Xu 2, 3 , Li Chen 1 , Zhaohui Tang 2, 3
Affiliation  

Despite the polymeric vascular disrupting agent (poly(L‐glutamic acid)‐graft‐methoxy poly(ethylene glycol)/combretastatin A4) nanoparticles can efficiently inhibit cancer growth, their further application is still a challenge owing to the tumor recurrence and metastasis after treatment. In this study, two poly(L‐glutamic acid)‐drug conjugates for chemo‐and photodynamic combination therapy are fabricated. PLG‐g‐mPEG‐CA4 nanoparticles are prepared by combretastatin A4 (CA4) and poly(L‐glutamic acid)‐graft‐methoxy poly(ethylene glycol) (PLG‐g‐mPEG) using the Yamaguchi esterification reaction. PLG‐g‐mPEG‐TPP (TPP: 5, 10, 15, 20‐tetraphenylporphyrin) nanoparticles are constructed using PLG‐g‐mPEG and amine porphyrin through condensation reaction between carboxyl group of PLG‐g‐mPEG and amino group of porphyrin. The results showed that PLG‐g‐mPEG‐CA4 nanoparticles have good antitumor ability. PLG‐g‐mPEG‐TPP nanoparticles can produce singlet oxygen under the laser irradiation. Moreover, the combined therapy of PLG‐g‐mPEG‐CA4 and PLG‐g‐mPEG‐TPP nanoparticles has higher antitumor effect than the single chemotherapy or the single photodynamic therapy in vitro. The combination of CA4 nondrug and photodynamic therapy provides a new insight for enhancing the tumor therapeutic effect with vascular disrupting agents and other therapy.

中文翻译:

用于化学和光动力联合治疗的聚(L-谷氨酸)-药物偶联物

尽管聚合物血管破坏剂(聚(L-谷氨酸)-接枝-甲氧基聚(乙二醇)/考布他汀A4)纳米粒子可以有效抑制癌症生长,但由于治疗后肿瘤复发和转移,其进一步应用仍然是一个挑战. 在这项研究中,制备了两种用于化学和光动力联合治疗的聚(L-谷氨酸)-药物偶联物。PLG - g -mPEG-CA4 纳米颗粒是通过考布他汀 A4(CA4)和聚(L-谷氨酸)-接枝-甲氧基聚(乙二醇)(PLG- g- mPEG)使用山口酯化反应制备的。PLG- g-mPEG-TPP (TPP: 5, 10, 15, 20-四苯基卟啉)纳米颗粒是使用PLG- g- mPEG和胺卟啉通过PLG- g- mPEG的羧基和卟啉的氨基之间的缩合反应构建的。结果表明PLG- g -mPEG-CA4纳米颗粒具有良好的抗肿瘤能力。PLG - g -mPEG-TPP纳米颗粒在激光照射下可以产生单线态氧。此外,综合治疗PLG--mPEG-CA4和PLG--mPEG-TPP纳米粒子在体外具有比单一化疗或单一光动力疗法更高的抗肿瘤作用。CA4 非药物和光动力疗法的结合为使用血管破坏剂和其他疗法增强肿瘤治疗效果提供了新的见解。
更新日期:2020-10-11
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