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Tumor-Adhesive and pH-Degradable Microgels by Microfluidics and Photo-Cross-Linking for Efficient Antiangiogenesis and Enhanced Cancer Chemotherapy
journal contribution
posted on 2020-02-24, 19:06 authored by Xingmei Chen, Hongliang Qian, Haishi Qiao, Bin Dong, Enping Chen, Dechun Huang, Ting Wang, Wei ChenTumor angiogenesis
with the vascular network formation provides
nutrition and oxygen for cancer cells, promoting the proliferation
and metastasis of malignant tumors. Bevacizumab (Bev) as an efficient
antiangiogenic antibody is able to normalize the tumor vasculature
with better blood flow and reduced interstitial fluid pressure, allowing
drugs with more uniform distribution and deeper penetration into the
tumor; however, it is highly difficult to realize the simultaneous
delivery of Bev and anticancer drugs localized at the tumor tissue.
Here, we prepared tumor-adhesive and pH-degradable poly(vinyl alcohol)
(PVA) microgels for tumor-localized delivery of Bev and docetaxel
(DTX), to achieve efficient antiangiogenesis and enhanced cancer chemotherapy.
PVA microgels (∼200 μm) decorated with tissue-adhesive
dopamine (DA) moieties were fabricated by a combination of high-throughput
microfluidics technology and photo-cross-linking chemistry with a
considerable coencapsulation efficiency for Bev and DTX. PVA microgels
exhibited sustained drug release at the tumoral acidic conditions
as the microgel degradation, and DA moieties on the microgels facilitated
Bev with long retention at the tumor tissue, highly blocking the vascular
endothelial growth factor (VEGF) and inhibiting tumor angiogenesis,
as compared to free Bev or no DA-decorated microgels. In addition,
the antitumor activity on the 4T1-Luc breast tumor mouse model treated
with Bev/DTX-coloaded microgels showed obviously superior tumor growth
inhibition than the other treatment groups, in which the combinational
therapy efficacy of Bev and DTX mediated by the tumor-adhesive microgels
was further confirmed by the immunohistochemistry (IHC) analysis.
These PVA microgels with efficient antiangiogenesis and enhanced cancer
chemotherapy provide a highly potential platform to treat different
malignant tumors as well as the recurrent and metastatic tumors.