4.7 Article

Hypoxia-degradable and long-circulating zwitterionic phosphorylcholine-based nanogel for enhanced tumor drug delivery

期刊

ACTA PHARMACEUTICA SINICA B
卷 11, 期 2, 页码 560-571

出版社

INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES
DOI: 10.1016/j.apsb.2020.08.012

关键词

Hypoxia-degradable; Zwitterionic nanogel; Long blood circulation; Drug release; Drug delivery

资金

  1. National Key Research and Development Program of China [2017YFA0205200]
  2. National Natural Science Foundation of China [81903165, 81901857]
  3. Chinese Postdoctoral Foundation [2019M663361]

向作者/读者索取更多资源

Hypoxia-responsive nanogels have been developed for tumor drug delivery, showing superior drug release and tumor inhibition effects compared to other degradable nanogels. The synthesized (PMPC)-P-H nanogel exhibits ultra-long blood circulation, desirable immune compatibility, and high and long-lasting accumulation in tumor tissue, making it a promising nanocarrier for advanced tumor drug delivery.
Tumor microenvironment has been widely utilized for advanced drug delivery in recent years, among which hypoxia-responsive drug delivery systems have become the research hotspot. Although hypoxia-responsive micelles or polymersomes have been successfully developed, a type of hypoxia-degradable nanogel has rarely been reported and the advantages of hypoxia-degradable nanogel over other kinds of degradable nanogels in tumor drug delivery remain unclear. Herein, we reported the synthesis of a novel hypoxia-responsive crosslinker and the fabrication of a hypoxia-degradable zwitterionic poly(phosphorylcholine)-based ((PMPC)-P-H) nanogel for tumor drug delivery. The obtained (PMPC)-P-H nanogel showed ultra-long blood circulation and desirable immune compatibility, which leads to high and long-lasting accumulation in tumor tissue. Furthermore, (PMPC)-P-H nanogel could rapidly degrade into oligomers of low molecule weight owing to the degradation of azo bond in hypoxic environment, which leads to the effective release of the loaded drug. Impressively, (PMPC)-P-H nanogel showed superior tumor inhibition effect both in vitro and in vivo compared to the reduction-responsive phosphorylcholine-based nanogel, owing to the more complete drug release. Overall, the drug-loaded (PMPC)-P-H nanogel exhibits a pronounced tumor inhibition effect in a humanized subcutaneous liver cancer model with negligible side effects, which showed great potential as nanocarrier for advanced tumor drug delivery. (C) 2021 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.

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