Sequential delivery of VEGF siRNA and paclitaxel for PVN destruction, anti-angiogenesis, and tumor cell apoptosis procedurally via a multi-functional polymer micelle

Journal of Controlled Release : Official Journal of the Controlled Release Society
Yanfang YangYuling Liu

Abstract

Co-delivery of chemotherapy drugs and VEGF siRNA (siVEGF) to control tumor growth has been a research hotspot for improving cancer treatment. Current systems co-deliver siVEGF and chemo drugs into tumor cells simultaneously. Although effective, these systems do not flow to the abnormal blood vessels around tumor cells (vascular niche, PVN), which play an important role in the metastasis and deterioration of the tumor. Thus, we custom-synthesized triblock copolymer poly(ε-caprolactone)-polyethyleneglycol-poly(L-histidine) (PCL-PEG-PHIS) with previously synthesized folate-PEG-PHIS to construct a targeted multifunctional polymer micelle (PTX/siVEGF-CPPs/TMPM) to sequentially deliver siVEGF-CPPs (disulfide bond-linked siVEGF and cell-penetrating peptides) and paclitaxel (PTX). The sequential delivery vesicles showed the anticipated three-layered TEM structure and dual-convertible (surface charge- and particle size-reversible) features in the tumor environment (pH 6.5), which guaranteed the sequential release of siVEGF-CPPs and PTX in the tumor extracellular environment and tumor cells, respectively. To mimic the in vivo tumor environment, a double cell model was employed by co-culturing HUVECs and MCF-7 cells. Improved cell endocyt...Continue Reading

Citations

Mar 17, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jiayi PanVladimir P Torchilin
Jan 8, 2020·Pharmaceutics·Olga OsipovaEvgenia Korzhikova-Vlakh
Oct 24, 2020·ACS Combinatorial Science·Milad AshrafizadehPooyan Makvandi
Feb 9, 2021·International Journal of Pharmaceutics·Diana CostaAna Figueiras
Nov 30, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Muhammad Muzamil KhanVladimir P Torchilin
Apr 10, 2021·Biomaterials·Yachao ZhangShuangying Gui
Apr 1, 2021·Cellular Oncology (Dordrecht)·Qingshan HuangWei Guo
Aug 13, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Jian SunZhaowei Chen
Sep 3, 2021·International Journal of Nanomedicine·Lu TangZihao Cai
Oct 13, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Raut BholakantJan Feijen
Dec 12, 2020·Acta Pharmaceutica Sinica. B·Nitin Bharat CharbeFlavia C Zacconi

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