Journal
BIOMATERIALS SCIENCE
Volume 9, Issue 13, Pages 4755-4764Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/d1bm00531f
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Funding
- National Key Research and Development Program of China [2018YFC1106102, 2018YFA0902600]
- National Natural Science Foundation of China [51973112, 51690151, 81871329]
- Science Foundation of The Shanghai Municipal Science and Technology Commission [18JC1410800, 19JC1410300]
- Innovation Fund from Joint Research Center for Precision Medicine [IFPM2019A2]
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The study demonstrates the potential of a spherical nucleic acid nanogel platform for the co-delivery of different therapeutic oligonucleotides and combinatorial CpG-based immunotherapy. The nanogel efficiently triggers M1 type macrophage activation, inhibits M2 polarization, and increases CD8(+) T cell infiltration, effectively restraining tumor growth.
The immune system plays a key role in restraining tumor progression. Therefore, enhancing immune functions using immune stimulants, such as unmethylated CpG oligonucleotides, has emerged as a promising strategy for antitumor therapy. However, poor cellular uptake of negatively charged oligonucleotides and M2 polarization of tumor-associated macrophages remain two major challenges for CpG-based immunotherapy. Herein, we construct a spherical nucleic acid (SNA)-like nanogel assembled by a CpG-grafted polycaprolactone (CpG-g-PCL) brush and an anti-STAT3 siRNA crosslinker for synergistic tumor immunotherapy. After accumulation at the tumor site, this dual siRNA- and CpG-bearing nanogel (CpGgel-siSTAT3) can efficiently trigger M1 type macrophage activation and deter its M2 polarization via block STAT3 signaling, increase the intratumor CD8(+) T cell infiltration, and thus successfully restrain tumor growth. Our study demonstrates the new potential of a nucleic acid nanogel platform for the co-delivery of different therapeutic oligonucleotides and combinatorial CpG-based immunotherapy.
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