Reprogramming tumor microenvironment with precise photothermal therapy by calreticulin nanobody-engineered probiotics

Zheng, Liuhai1,2,3; Wang, Huifang1,2,3; Zhong, Xiaoru4; Jia, Lin5; Shi, Guangwei1,2,6,7; Bai, Chongzhi8; Yang, Runwei6,7; Huang, Zhenhui5; Jiang, Yuke1,2,9,10; Wei, Jinxi4; Dong, Zhiyu4; Li, Jiexuan4; Long, Ying4; Dai, Lingyun1,2; Li, Zhijie4; Chen, Chunbo1,2; Wang, Jigang1,2,9,10

2025-03-01

10.1016/j.biomaterials.2024.122809

BIOMATERIALS   影响因子和分区

0142-9612

1878-5905

Targeted therapies have revolutionized traditional cancer treatments by precisely targeting tumor cells, enhancing efficacy and safety. Despite this advancement, the proportion of cancer patients eligible for such therapies remains low due to the absence of suitable targets. Here, we investigate whether the translocation of the immunogenic cell death (ICD) marker calreticulin (CALR) from the endoplasmic reticulum (ER) to the cell surface following ICD induction can serve as a target for targeted therapies. To target CALR, a nanobody Nb215 identified from a na & iuml;ve VHH phage library with high binding affinity to both human and mouse CALR was employed to engineer probiotic EcN 1917. Our results demonstrated that CALR nanobody-modified EcN-215 coupled with the photothermal dye indocyanine green (ICG) was able to exert NIR-II imaging-guide photothermal therapy (PTT). Moreover, PTT with EcN-215/ICG can reshape the tumor microenvironment by enhancing the infiltration of CD45(+)CD3(+) T cells and CD11b(+)F4/80(+) macrophages. Furthermore, the antitumor activity of CALR-targeted EcN-215/ICG is synergistically enhanced by blocking CD47-SIRP alpha axis. Collectively, our study provides a proof of concept for CALR-targeted therapy. Given that CALR translocation can be induced by various anticancer therapies across numerous tumor cell lines, CALR-targeted therapies hold promise as a novel approach for treating multiple types of cancers.

Targeted therapies Immunogenic cell death CALR Nanobody Photothermal therapy

SCI

英语

通讯

National Key Research and Development Program of China[2022YFC2303600] ; Key Special Project of "Strategic Science and Technology Innovation Cooperation" from National Key R D Program[2023YFE0204500] ; Shenzhen Science and Technology Innovation Committee[RCBS20210706092213007] ; Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences["CI2023D003","CI2021B014","CI2023D008"] ; CACMS Innovation Fund["CI2023E002","CI2021A05101","CI2021A05104"] ; Science and Technology Foundation of Shenzhen["JCYJ20210324115800001","JCYJ20210324113608023","JCYJ202001 09120205924"] ; Shenzhen Medical Research Fund[B2302051] ; Shenzhen Science and Technology Innovation Committee (SZSTI)[RCYX202210080 92950121] ; National Natural Science Foundation of China["82373775","32101219","82103140"] ; Natural Science Foundation of Top Talent of SZTU[GDRC202125] ; Shenzhen Science and Technology Innovation Commission[JCYJ20200109120205924] ; Shenzhen Key Medical Discipline Con-struction Fund[SZXK046] ; Guangdong Basic and Applied Basic Research Foundation["2021A1515012164","2022A1515110745","2021A 1515111188"] ; International Science and Technology Cooperation for Shenzhen Technology Innovation Plan[GJHZ20200731095411034] ; Shenzhen Governmental Sustainable Development Fund[KCXFZ2 0201221173612034] ; Shenzhen key Laboratory of Kidney Diseases[ZDSYS201504301616234] ; Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties[SZGSP001]

Engineering ; Materials Science

Engineering, Biomedical ; Materials Science, Biomaterials

WOS:001320592100001

ELSEVIER SCI LTD

Web of Science

1.Jinan Univ, Shenzhen Peoples Hosp, Clin Med Coll 2, Shenzhen Clin Res Ctr Geriatr,Guangdong Prov Clin, Shenzhen 518020, Peoples R China
2.Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen 518020, Peoples R China
3.Jinan Univ, Postdoctoral Sci Res Stn Basic Med, Guangzhou 510632, Guangdong, Peoples R China
4.Southern Univ Sci & Technol, Jinan Univ, Affiliated Hosp 1, Clin Med Coll 2,Shenzhen Peoples Hosp,Dept Hyperba, Shenzhen 518020, Guangdong, Peoples R China
5.Shenzhen Technol Univ, Coll Pharm, Shenzhen 518118, Peoples R China
6.Southern Med Univ, Shunde Hosp, Peoples Hosp Shunde Foshan 1, Dept Neurosurg, Foshan 528399, Peoples R China
7.Southern Med Univ, Shunde Hosp, Peoples Hosp Shunde Foshan 1, Med Res Ctr, Foshan 528399, Peoples R China
8.Shanxi Prov Hosp Tradit Chinese Med, Cent Lab, Taiyuan 030012, Peoples R China
9.China Acad Chinese Med Sci, Inst Chinese Mat Med, Artemisinin Res Ctr, State Key Lab Qual Ensurance & Sustainable Use Dao, Beijing 100700, Peoples R China
10.Henan Univ, Sch Pharm, State Key Lab Antiviral Drugs, Kaifeng 475004, Peoples R China

Zheng, Liuhai,Wang, Huifang,Zhong, Xiaoru,et al. Reprogramming tumor microenvironment with precise photothermal therapy by calreticulin nanobody-engineered probiotics[J]. BIOMATERIALS,2025,314.

Zheng, Liuhai.,Wang, Huifang.,Zhong, Xiaoru.,Jia, Lin.,Shi, Guangwei.,...&Wang, Jigang.(2025).Reprogramming tumor microenvironment with precise photothermal therapy by calreticulin nanobody-engineered probiotics.BIOMATERIALS,314.

Zheng, Liuhai,et al."Reprogramming tumor microenvironment with precise photothermal therapy by calreticulin nanobody-engineered probiotics".BIOMATERIALS 314(2025).