Journal
ADVANCED FUNCTIONAL MATERIALS
Volume 30, Issue 7, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adfm.201906922
Keywords
cancer immunotherapy; chemoimmunotherapy; drug delivery; hydrogel
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Funding
- Soochow University
- Program for Jiangsu Specially Appointed Professors
- Collaborative Innovation Center of Suzhou Nano Science and Technology, the 111 Project
- National Natural Science Foundation of China [31900988, 81772773, 81672560, 81302275]
- Natural Science Foundation of Jiangsu Province [SBK2019040088]
- Jiangsu Province Six Talent Peaks Project [SWYY-110]
- Jiangsu Provincial Medical Youth Talent [QNRC2016753]
- Project of Jiangsu Provincial Maternal and Child Health Association [FYX201709]
- Gusu Medical Talent Project [GSWS2019034]
- Postgraduate Research & Practice Innovation Program of Jiangsu Province [SJCX18_0853]
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Unsatisfied cytoreductive surgery predicts worse clinical outcomes. Previous studies have found that cyclophosphamide (CTX) is a rhythmic immune modulator that can target suppressive regulatory immune cells and meanwhile enhance effector cells. Here, a therapeutic scaffold is engineered based on a fibrin hydrogel to codeliver CTX and anti-PD-L1 antibody (aPDL1) for the prevention of cancer recurrence postsurgery. It is demonstrated that the sequential release of CTX and aPDL1 from the fibrin hydrogel can lead to selective depletion of regulatory T cells (Treg) in the residual tumor, which would then synergize the immune checkpoint blockade therapy. The therapeutic benefit is demonstrated in an orthotopic breast tumor and an orthotopic ovarian tumor model after incomplete resection of primary tumors. In this work, the strategy provides a clinically valuable option for preventing cancer recurrence postsurgery.
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