Combining immune checkpoint blockade with ATP-based immunogenic cell death amplifier for cancer chemo-immunotherapy.
10.1016/j.apsb.2022.05.008
- Author:
Jiulong ZHANG
1
;
Xiaoyan SUN
1
;
Xiufeng ZHAO
2
;
Chunrong YANG
3
;
Menghao SHI
1
;
Benzhuo ZHANG
4
;
Haiyang HU
1
;
Mingxi QIAO
1
;
Dawei CHEN
1
;
Xiuli ZHAO
1
Author Information
1. School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
2. Department of Oncology, Affiliated Hongqi Hospital of Mudanjiang Medical College, Mudanjiang 157011, China.
3. Department of Pharmacy, Shantou University Medical College, Shantou 515041, China.
4. Department of Neurology, The Second Affiliated Hospital of Mudanjiang Medical College, Mudanjiang 157009, China.
- Publication Type:Journal Article
- Keywords:
ATP;
Coordination polymer nanoparticles;
Fenton reaction;
Immune checkpoint blockade;
Immunogenic cell death amplifier;
Phenylboric acid;
pH/ROS sensitive
- From:
Acta Pharmaceutica Sinica B
2022;12(9):3694-3709
- CountryChina
- Language:English
-
Abstract:
Amplifying "eat me signal" during tumor immunogenic cell death (ICD) cascade is crucial for tumor immunotherapy. Inspired by the indispensable role of adenosine triphosphate (ATP, a necessary "eat me signal" for ICD), a versatile ICD amplifier was developed for chemotherapy-sensitized immunotherapy. Doxorubicin (DOX), ATP and ferrous ions (Fe2+) were co-assembled into nanosized amplifier (ADO-Fe) through π‒π stacking and coordination effect. Meanwhile, phenylboric acid-polyethylene glycol-phenylboric acid (PBA-PEG-PBA) was modified on the surface of ADO-Fe (denoted as PADO-Fe) by the virtue of d-ribose unit of ATP. PADO-Fe could display active targetability against tumor cells via sialic acid/PBA interaction. In acidic microenvironment, PBA-PEG-PBA would dissociate from amplifier. Moreover, high H2O2 concentration would induce hydroxyl radical (·OH) and oxygen (O2) generation through Fenton reaction by Fe2+. DOX and ATP would be released from the amplifier, which could induce ICD effect and "ICD adjuvant" to amplify this process. Together with programmed death ligands 1 (PD-L1) checkpoint blockade immunotherapy, PADO-Fe could not only activate immune response against primary tumor, but also strong abscopal effect against distant tumor. Our simple and multifunctional ICD amplifier opens a new window for enhancing ICD effect and immune checkpoint blockade therapy.
