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Immune checkpoint blockade is a revolutionary advance in oncology treatment, but drug resistance has resulted in only a small percentage of cancer patients responding
to the therapy.
In some tumors, cancer cells prevent lymphocyte infiltration, and most infiltrating lymphocytes function in a depleted state
.
Therefore, how to promote lymphocyte infiltration and reverse lymphocyte killing function has become a key issue
in tumor immune checkpoint blockade therapy.
to the therapy.
In some tumors, cancer cells prevent lymphocyte infiltration, and most infiltrating lymphocytes function in a depleted state
.
Therefore, how to promote lymphocyte infiltration and reverse lymphocyte killing function has become a key issue
in tumor immune checkpoint blockade therapy.
In response to the above problems, Li Yaping's team from the Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhang Zhiwen's team from the School of Pharmacy of Fudan University, and Zhang Ao's team from the School of Pharmacy of Shanghai Jiao Tong University, designed and constructed an intelligent biomimetic drug delivery system (MNGs) loaded with gemcitabine prodrugs, which is used to improve the infiltration of lymphocytes in tumors and further improve the anti-tumor effect
of immune checkpoint blockers.
The study was published online in ACS Nano
on December 17, 2022.
of immune checkpoint blockers.
The study was published online in ACS Nano
on December 17, 2022.
In this study, acid-sensitive amphiphilic polymers (PEG-PDPA) and enzyme-sensitive gemcitabine prodrugs (C14-Gem) were designed and synthesized into micelles.
MNGs
are prepared by overlay of macrophage membranes.
Due to the biomimetic properties of macrophage membranes, MNGs can accumulate at the tumor site and penetrate into the deep part of the tumor, improve the infiltration of lymphocytes inside the tumor and the expression of PD-L1 at the immune checkpoint, and reactivate the anti-tumor killing function
of lymphocytes in collaboration with PD-L1 monoclonal antibody.
MNGs
are prepared by overlay of macrophage membranes.
Due to the biomimetic properties of macrophage membranes, MNGs can accumulate at the tumor site and penetrate into the deep part of the tumor, improve the infiltration of lymphocytes inside the tumor and the expression of PD-L1 at the immune checkpoint, and reactivate the anti-tumor killing function
of lymphocytes in collaboration with PD-L1 monoclonal antibody.
The results showed that compared with the MNGs monotherapy group, the combination of MNGs+PD-L1 monoclonal antibody reduced CD3+CD8+ T cells and natural killer cells by 31.
77% and 30.
63%, respectively, while the interferon-γ-positive subtype increased by 2.
83-fold and 3.
17-fold
, respectively.
Produce considerable therapeutic effects
in a variety of tumor models.
Therefore, MNGs provide a new idea
for promoting lymphocyte infiltration and synergistic PD-L1 monoclonal antibody to restore lymphocyte tumor killing ability.
77% and 30.
63%, respectively, while the interferon-γ-positive subtype increased by 2.
83-fold and 3.
17-fold
, respectively.
Produce considerable therapeutic effects
in a variety of tumor models.
Therefore, MNGs provide a new idea
for promoting lymphocyte infiltration and synergistic PD-L1 monoclonal antibody to restore lymphocyte tumor killing ability.
The preparation of MNGs and their synergy with PD-L1 antibodies improved the effect of anti-tumor immunotherapy
Professor Li Yaping of Shanghai Institute of Materia Medica, researcher Zhang Zhiwen of Fudan University and Professor Zhang Ao of Shanghai Jiao Tong University are co-corresponding authors of the paper, and Li Jie, postdoctoral fellow of Shanghai Institute of Materia Medica, and Yao Wu, a graduate student of Shanghai Institute of Materia Medica-Fudan University, are the first authors
of the paper.
The paper was supported
by the National Key Research and Development Program of China and the National Natural Science Foundation of China.
of the paper.
The paper was supported
by the National Key Research and Development Program of China and the National Natural Science Foundation of China.
Full text link: https://pubs.
acs.
org/doi/10.
1021/acsnano.
2c07861
acs.
org/doi/10.
1021/acsnano.
2c07861
(Contributing department: Li Yaping's research group; Contributor: Li Jie)
