Protein stabilized polymeric nanoparticles inspired relay drug delivery for tackling post-chemotherapeutic metastasis

• Published in: Chemical engineering journal (Lausanne, Switzerland : 1996) Switzerland : 1996), 2022-01, Vol.427, p.131672, Article 131672
• Main Authors: Cheng, Hao, Jiang, Zijun, Sun, Chenkai, Wang, Zhen, Han, Guochen, Chen, Xin, Li, Tianyi, Fan, Zhechen, Zhang, Feng, Yang, Xiaoyu, Lv, Lingyu, Zhang, Huaqing, Zhou, Jianping, Ding, Yang
• Format: Article
• Language: English
• Subjects: Bio-responsive disassembly; Metastasis inhibition post chemotherapy; Protein stabilization; Relay drug delivery; Spatially-separated multi-drug shielding
• ISSN: 1385-8947; 1873-3212
• DOI: 10.1016/j.cej.2021.131672

[Display omitted] •Protein stabilized polymeric nanoparticles for optimal multi-drug shielding and compatibility.•Relay delivery of chemotherapeutics and genetic drugs in tumour cells for tackling chemotherapy promoted metastasis.•Advanced therapeutic efficacy of primary tumour shrinkage and complete metastatic nodule elimination. The pro-metastatic potential of chemotherapy limits its therapeutic benefits against invasive cancer. Herein, a protein stabilized polymeric nanoparticle inspired relay drug delivery platform was developed to address post-chemotherapeutic metastasis. An ROS-responsive Phenylboronic acid (PBA)-Rich cationic polymer (RPP) bridges Doxorubicin (Dox) coordination and Snail-targeted siRNA (siSnail) compression, and natural apolipoprotein A-I (apoA-I) is attracted by surface electron-deficient PBA moieties for nanoparticle shaping, drug biostability, and tumour-penetration. The spatially-separated structure enables a timing-controlled relay drug delivery in tumour cells, where Dox gives a prior release phase by acidity, and RPP polymer is subsequently disintegrated by concentrated ROS for rapid siSnail liberation. In dual therapy, Dox pre-treatment upregulated pro-metastatic factors and aggravated metastasis, but subsequent liberation by siSnail silenced the central metastatic regulator of Epithelial-mesenchymal transition (EMT). The terminal nanoparticles exhibited advanced therapeutic efficacy, achieving primary tumour shrinkage (tumour weight inhibition, TWI of ~86.15%) and complete metastatic nodule elimination. This work promises to improve the clinical benefits of chemotherapy against invasive cancer.