Department of Chemistry, Northeast Normal University, 5268 Renmin Street, Changchun, 130024, P. R. China.
Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, 130022, P. R. China.
Macromol Biosci. 2021 Jan;21(1):e2000192. doi: 10.1002/mabi.202000192. Epub 2020 Oct 11.
Despite the polymeric vascular disrupting agent (poly( -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( -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( -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.
尽管聚合血管破坏剂（聚（-谷氨酸）-接枝-甲氧基聚乙二醇/康普瑞汀 A4）纳米粒可以有效地抑制肿瘤生长，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。在本研究中，制备了两种用于化疗和光动力联合治疗的聚（-谷氨酸）-药物偶联物。通过 Yamaguchi 酯化反应，将康普瑞汀 A4（CA4）和聚（-谷氨酸）-接枝-甲氧基聚乙二醇（PLG-g-mPEG）用于制备 PLG-g-mPEG-CA4 纳米粒。通过 PLG-g-mPEG 和胺卟啉之间的缩合反应，使用 PLG-g-mPEG 和胺卟啉构建了 PLG-g-mPEG-TPP（TPP：5、10、15、20-四苯基卟啉）纳米粒。结果表明，PLG-g-mPEG-CA4 纳米粒具有良好的抗肿瘤能力。PLG-g-mPEG-TPP 纳米粒在激光照射下可产生单线态氧。此外，PLG-g-mPEG-CA4 和 PLG-g-mPEG-TPP 纳米粒联合治疗的体外抗肿瘤效果高于单一化疗或单一光动力治疗。CA4 非药物与光动力治疗的结合为提高血管破坏剂和其他治疗方法的肿瘤治疗效果提供了新的思路。
