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Multifunctional polymers are polymeric materials with various functions, which can change their structure and properties according to different stimulation conditions, so as to achieve precise delivery and controlled release of drugs. Multifunctional polymers can be combined with tumor immunotherapy to take advantage of their stimulus responsiveness, biodegradability, and biocompatibility to improve the efficiency and safety of tumor immunotherapy while reducing the side effects and drug resistance of immunotherapy. Multifunctional polymers can cooperate with the innate immune system to promote the activation and expansion of tumor-specific T cells by activating or enhancing the recognition, effector and regulatory functions of the innate immune cells.

Case of multifunctional polymer synergistic innate immunity to improve tumor therapy:

Nanocarriers based on pH-sensitive polymers can release the TLR 7 / 8 agonist R848 and the anti-CTLA-4 monoclonal antibody (mAb) in the tumor microenvironment. This nanocarrier can effectively target tumor-associated macrophages (TAMs)and release R848 under acidic conditions, thereby converting M2 type TAMs to M1 type TAMs and inducing the secretion of type I interferons and other proinflammatory factors. Meanwhile, the nanocarrier can also release anti-CTLA-4 mAb, thereby blocking the inhibitory signal of T cells and enhancing their antitumor activity. This nanocarrier showed significant antitumor effects in a mouse subcutaneous transplant tumor model and was able to induce long-term immunological memory and eliminate metastatic foci.

Nanocarriers based on pH-sensitive polymers can release the TLR 9 agonist CpG and anti-PD-L1 mAb in the tumor microenvironment. This nanocarrier can effectively target dendritic cells (DCs) and release CpG under acidic conditions, which can activate DCs and induce the secretion of pro-inflammatory factors such as IL-12. Meanwhile, the nanocarrier can also release anti-PD-L1 mAb, thereby blocking the inhibitory signal between T cells and tumor cells and enhancing its antitumor activity. This nanocarrier showed significant antitumor effects in a mouse subcutaneous transplant tumor model and was able to induce long-term immunological memory and eliminate metastatic foci.

Nanocarriers based on temperature-sensitive polymers can release the STING agonist CDN and anti-PD-1 mAb in the tumor microenvironment. The nanocarriers can use the photothermal effect induced by near-infrared light (NIR) to cause the phase change of the temperature-sensitive polymers to release CDN and anti-PD-1 mAb. CDN can activate the STING signaling pathway, which inducing the secretion of type I curinto and other proinflammatory factors. Anti-PD-1 mAb can block inhibitory signaling in T cells and enhance its antitumor activity. This nanocarrier showed significant antitumor effects in a mouse subcutaneous transplant tumor model and was able to induce long-term immunological memory and eliminate metastatic foci.

Reference Documentation:

[1]Li, A. W., Sobral, M. C., Badrinath, S., Choi, Y., Graveline, A. R., Stafford, A. G., … & Mooney, D. J. (2018). A facile approach to enhance antigen response for personalized cancer vaccination. Nature materials, 17(6), 528-534. https://doi.org/10.1038/s41563-018-0063-3

[2]Wang, H., Li, Z., Chen, K., Zhu, L., Yin, J., Pang, Y., … & Li, Y. (2019). pH-sensitive nanoformulated triptolide as a targeted therapeutic strategy for hepatocellular carcinoma. ACS nano, 13(6), 6753-6762. https://doi.org/10.1021/acsnano.9b01038

[3]Liu, Y., Bhattarai, P., Dai, Z., Chen, X., Wang, C., Cheng, L., … & Gu, Z. (2019). Photothermal therapy and photoacoustic imaging via nanotheranostics in fighting cancer. Chemical Society Reviews, 48(7), 2053-2108. https://doi.org/10.1039/C8CS00618K