SCIENCE CHINA Chemistry, Volume 62 , Issue 12 : 1557-1560(2019) https://doi.org/10.1007/s11426-019-9588-4

Engineered nanoparticles circumvent the adaptive treatment tolerance to immune-checkpoint blockade therapy

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  • ReceivedJun 3, 2019
  • AcceptedAug 16, 2019
  • PublishedAug 29, 2019


There is no abstract available for this article.

Funded by

the National Natural Science Foundation of China(31630027,31430031,81601603)

the National Distinguished Young Scholars grant(31225009)

the NSFC-DFG Project(31761133013)

and the External Cooperation Program of the Chinese Academy of Science(121D11KYSB20160066)


We appreciate Prof. Massimo Bottini from University of Rome Tor Vergata, who provided many thoughtful suggestions and kind edit to our manuscript. This work was partially supported by the National Natural Science Foundation of China (31630027, 31430031, 81601603), the National Distinguished Young Scholars Grant (31225009), the NSFC-DFG Project (31761133013), and the External Cooperation Program of the Chinese Academy of Sciences (121D11KYSB20160066).

Interest statement

The authors declare that they have no conflict of interest.


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  • Scheme 1

    Engineered nanoparticles can modulate and reverse the adaptive treatment tolerance (ATT) of tumors to immune-checkpoint blockade (ICB) therapy and potentiate antitumor efficacy. CTL, cytotoxic T lymphocyte; PD-L1, programmed death-ligand 1; TME, tumor microenvironment (color online).

  • Table 1   Table of engineered nanoparticles-based strategies that can overcome ATT to ICB therapy

    Reason of ATT issue

    Types of nanoparticles



    Inadequate activation of T cells after radiotherapy.

    Antibodies decorated poly(lactic-co-glycolic acid) (PLGA) nanoparticles.

    Capture and transport the tumor-derived protein antigens.


    Inadequate activation of T cells after radiotherapy.

    Sodium alginate nanoparticles containing catalase (Cat) labelled with the therapeutic 131I radioisotope.

    Long-term relief of tumour hypoxia and efficient activation of immune cells after low radioactivity doses.


    Inadequate activation of T cells after radiotherapy.

    Self-assembled nanoscale coordination polymer (NCP) core-shell nanoparticles carrying OxPt in the core and DHA in the shell (OxPt/DHA).

    ROS generation is harnessed for immune activation to synergize with an anti-PD-L1 antibody for the treatment of murine colorectal cancer.


    Inadequate activation of T cells after radiotherapy.

    Two kinds of nanoscale metal-organic framework: 5,15-di(p-benzoato) porphyrin-Hf (DBP-Hf) and 5,10,15,20-tetra(p-nzoato)porphyrin-Hf (TBP-Hf).

    In situ vaccination and indoleamine 2,3-dioxygenase inhibition by combining radiotherapy-radiodynamic therapy with checkpoint blockade immunotherapy.


    Inefficient activation and expansion of T cells.

    Mesoporous silica nanorods decorated with antibodies for CD28 and CD3.

    Sustained IL-2 release and highly efficient expansion of primary T cells.


    Systemic generation of PD-L1 presenting exosomes by cancer cells.

    PD-L1 antibody-presenting platelets.

    Disassemble into PD-L1 antibody-presenting nanovesicles in the wound sites post-surgery and disrupt the PD-1/PD-L1 axis.


    Systemic generation of PD-L1 presenting exosomes by cancer cells.

    Engineered nanovesicles derived from PD-1 expressing 293T cells.

    Block the PD-1/PD-L1 at the surface of cancer cells and inhibit the indoleamine 2,3-dioxygenase.


    Intracellular generation of PD-L1.

    Acid-activatable cationic nanoparticles (POP/siRNA).

    Transmit siRNA into cancer cells to knockdown the expression of PD-L1.


    Generation of antidrug antibodies (ADAs) after treatments with therapeutic antibodies.

    Rapamycin-loaded PLGA nanoparticles.

    Mitigate the formation of inhibitory ADAs.



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