Multifunctional Calcium-Manganese Nanomodulator Provides Antitumor Treatment and Improved Immunotherapy via Reprogramming of the Tumor Microenvironment

Luo，Guanghong1,5; Li，Xing3; Lin，Jihui1,2; Ge，Gao11; Fang，Jiangli6; Song，Wangze12; Xiao，Gary Guishan8,12; Zhang，Bo1,4; Peng，Xiaojun7; Duo，Yanhong5,6,9; Tang，Ben Zhong10

2023

10.1021/acsnano.3c01215

ACS Nano   Impact Factor & Quartile

1936-0851

1936-086X

Ions play a vital role in regulating various biological processes, including metabolic and immune homeostasis, which involves tumorigenesis and therapy. Thus, the perturbation of ion homeostasis can induce tumor cell death and evoke immune responses, providing specific antitumor effects. However, antitumor strategies that exploit the effects of multiion perturbation are rare. We herein prepared a pH-responsive nanomodulator by coloading curcumin (CU, a Ca enhancer) with CaCO and MnO into nanoparticles coated with a cancer cell membrane. This nanoplatform was aimed at reprogramming the tumor microenvironment (TME) and providing an antitumor treatment through ion fluctuation. The obtained nanoplatform, called CM NPs, could neutralize protons by decomposing CaCO and attenuating cellular acidity, they could generate Ca and release CU, elevating Ca levels and promoting ROS generation in the mitochondria and endoplasmic reticulum, thus, inducing immunogenic cell death. Mn could decompose the endogenous HO into O to relieve hypoxia and enhance the sensitivity of cGAS, activating the cGAS-STING signaling pathway. In addition, this strategy allowed the reprogramming of the immune TME, inducing macrophage polarization and dendritic cell maturation via antigen cross-presentation, thereby increasing the immune system’s ability to combat the tumor effectively. Moreover, the as-prepared nanoparticles enhanced the antitumor responses of the αPD1 treatment. This study proposes an effective strategy to combat tumors via the reprogramming of the tumor TME and the alteration of essential ions concentrations. Thus, it shows great potential for future clinical applications as a complementary approach along with other multimodal treatment strategies.

antitumor therapy calcium−manganese nanomodulator immunotherapy reprogramming tumor microenvironment

SCI

English

NI Journal Papers

Corresponding

WOS:001039798900001

2-s2.0-85168427958

Scopus

1.School of Medicine,The 2nd Affiliated Hospital,The Chinese University of HongKong,Shenzhen,Guangdong (CUHK-Shenzhen),518172,China
2.School of Nursing,Southwest Medical University,Luzhou,Sichuan,646000,China
3.School of Medicine,Southern University of Science and Technology,Shenzhen,518055,China
4.Department of Neurosurgery,The Shenzhen Luohu Hospital Group,The Third Affiliated Hospital of Shenzhen University,Shenzhen,518001,China
5.Department of Radiation Oncology,Shenzhen People’s Hospital (The Second Clinical Medical College,Jinan University; The First Affiliated Hospital,Southern University of Science and Technology),Shenzhen,Guangdong,518020,China
6.Department of Microbiology,Tumor and Cell Biology (MTC),Karolinska Institutet,Stockholm,171 77,Sweden
7.State Key Laboratory of Fine Chemicals,School of Chemical Engineering,Dalian University of Technology,Dalian,116024,China
8.Research Center for Cancer Metabolism,College of Pharmacology,Shenzhen University of Technology,Chinese Academy of Sciences,Shenzhen,518118,China
9.Key Lab for New Drug Research of TCM,Research Institute of Tsinghua University in Shenzhen,Shenzhen,Guangdong,518057,China
10.Shenzhen Institute of Aggregate Science and Technology,School of Science and Engineering,The Chinese University of Hong Kong,Shenzhen,Shenzhen,Guangdong,518172,China
11.Department of Laboratory Medicine,The Third Xiangya Hospital,Central South University,Changsha,410013,China
12.State Key Laboratory of Fine Chemicals,Department of Pharmacology,School of Chemical Engineering,Dalian University of Technology,Dalian,116024,China

Luo，Guanghong,Li，Xing,Lin，Jihui,et al. Multifunctional Calcium-Manganese Nanomodulator Provides Antitumor Treatment and Improved Immunotherapy via Reprogramming of the Tumor Microenvironment[J]. ACS Nano,2023.

Luo，Guanghong.,Li，Xing.,Lin，Jihui.,Ge，Gao.,Fang，Jiangli.,...&Tang，Ben Zhong.(2023).Multifunctional Calcium-Manganese Nanomodulator Provides Antitumor Treatment and Improved Immunotherapy via Reprogramming of the Tumor Microenvironment.ACS Nano.

Luo，Guanghong,et al."Multifunctional Calcium-Manganese Nanomodulator Provides Antitumor Treatment and Improved Immunotherapy via Reprogramming of the Tumor Microenvironment".ACS Nano (2023).