Flower-Like Nanosensors for Photoacoustic-Enhanced Lysosomal Escape and Cytoplasmic Marker-Activated Fluorescence: Enabling High-Contrast Identification and Photothermal Ablation of Minimal Residual Disease in Breast Cancer
Lin Li
Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, No. 174 Shazheng Road, Chongqing, 400044 China
Search for more papers by this authorYuxin Xing
Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, No. 174 Shazheng Road, Chongqing, 400044 China
Search for more papers by this authorYuhua Chen
Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, No. 174 Shazheng Road, Chongqing, 400044 China
Search for more papers by this authorKunlin Li
Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, No. 174 Shazheng Road, Chongqing, 400044 China
Search for more papers by this authorYunyun Wu
Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, No. 174 Shazheng Road, Chongqing, 400044 China
Search for more papers by this authorKaiyong Cai
Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, No. 174 Shazheng Road, Chongqing, 400044 China
Search for more papers by this authorCorresponding Author
Lu Wang
Department of Clinical Laboratory, Laboratory Medicine Center, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), No.158 Shangtang Road, Hangzhou, Zhejiang, 310014 China
School of Laboratory Medicine and Bioengineering, Hangzhou Medical College, No.8 Yikang Road, Hangzhou, Zhejiang, 311399 China
E-mail: wanglu622@hmc.edu.cn; jixizhang@cqu.edu.cn
Search for more papers by this authorCorresponding Author
Jixi Zhang
Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, No. 174 Shazheng Road, Chongqing, 400044 China
E-mail: wanglu622@hmc.edu.cn; jixizhang@cqu.edu.cn
Search for more papers by this authorLin Li
Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, No. 174 Shazheng Road, Chongqing, 400044 China
Search for more papers by this authorYuxin Xing
Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, No. 174 Shazheng Road, Chongqing, 400044 China
Search for more papers by this authorYuhua Chen
Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, No. 174 Shazheng Road, Chongqing, 400044 China
Search for more papers by this authorKunlin Li
Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, No. 174 Shazheng Road, Chongqing, 400044 China
Search for more papers by this authorYunyun Wu
Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, No. 174 Shazheng Road, Chongqing, 400044 China
Search for more papers by this authorKaiyong Cai
Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, No. 174 Shazheng Road, Chongqing, 400044 China
Search for more papers by this authorCorresponding Author
Lu Wang
Department of Clinical Laboratory, Laboratory Medicine Center, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), No.158 Shangtang Road, Hangzhou, Zhejiang, 310014 China
School of Laboratory Medicine and Bioengineering, Hangzhou Medical College, No.8 Yikang Road, Hangzhou, Zhejiang, 311399 China
E-mail: wanglu622@hmc.edu.cn; jixizhang@cqu.edu.cn
Search for more papers by this authorCorresponding Author
Jixi Zhang
Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, No. 174 Shazheng Road, Chongqing, 400044 China
E-mail: wanglu622@hmc.edu.cn; jixizhang@cqu.edu.cn
Search for more papers by this authorAbstract
The clearance of minimal residual disease (MRD) after breast cancer surgery is crucial for inhibiting metastasis and recurrence. However, the most promising biomarker-activated fluorescence imaging strategies encounter accessibility issues of the delivered sensors to cytoplasmic targets. Herein, a flower-like composite nanosensor with photoacoustic (PA) effect-enhanced lysosomal escape and cytoplasmic marker-activated fluorescence is developed to address this challenge. Specifically, the incorporation of Co2+ into the synthesis of 2D Zn2+-derived metal–organic frameworks enabled rapid dopamine polymerization and deposition. Subsequently, the composite nanoflower (FHN), characterized by an average size of ≈80 nm and petal thickness of ≈6 nm, is formed through the sealing of micropores and simultaneous cross-linking of nanosheets. The pronounced reduction in thermal conductivity of FHN, and superposition of interpetal thermal fields under a pulsed laser (PL), lead to enhanced PA effect and membrane permeability. Thereby, nanosensors efficiently escape from lysosomes resulting in synergistic fluorescence activation by dual-factors (ATP, miRNA-21) and DNA probes installed on FHN. A subsequently high tumor-to-normal tissue signal ratio (TNR) of 17.4 lead to precise guidance of NIR irradiation for efficient MRD eradication and recurrence inhibition. This study provides a new approach for high-contrast identification and precise ablation of MRD based on the synergistic response of endogenous and exogenous factors.
Conflict of Interest
The authors declare no conflict of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supporting Information
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Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1a) S. Lei, R. Zheng, S. Zhang, S. Wang, R. Chen, K. Sun, H. Zeng, J. Zhou, W. Wei, Cancer Communications 2021, 41, 1183; b) J. Li, Z. Ge, K. Toh, X. Liu, A. Dirisala, W. Ke, P. Wen, H. Zhou, Z. Wang, S. Xiao, J. F. R. Van Guyse, T. A. Tockary, J. Xie, D. Gonzalez-Carter, H. Kinoh, S. Uchida, Y. Anraku, K. Kataoka, Adv. Mater. 2021, 33, 2105254.
- 2a) K. L. Britt, J. Cuzick, K.-A. Phillips, Nat. Rev. Cancer 2020, 20, 417; b) M. Riis, Annals of Medicine and Surgery 2020, 56, 95.
- 3a) D. A. Mahvi, R. Liu, M. W. Grinstaff, Y. L. Colson, C. P. Raut, Cancer Journal for Clinicians 2018, 68, 488; b) C. Corti, G. Antonarelli, C. Criscitiello, N. U. Lin, L. A. Carey, J. Cortés, P. Poortmans, G. Curigliano, Cancer Treat. Rev. 2022, 103, 102324.
- 4a) K. Pantel, C. Alix-Panabières, Nat. Rev. Clin. Oncol. 2019, 16, 409; b) Z. Zhang, G. Kuang, S. Zong, S. Liu, H. Xiao, X. Chen, D. Zhou, Y. Huang, Adv. Mater. 2018, 30, 1803217.
- 5a) L. J. Lauwerends, P. B. A. A. van Driel, R. J. Baatenburg de Jong, J. A. U. Hardillo, S. Koljenovic, G. Puppels, L. Mezzanotte, C. W. G. M. Löwik, E. L. Rosenthal, A. L. Vahrmeijer, S. Keereweer, Lancet Oncol. 2021, 22, e186; b) Z. Hu, C. Fang, B. Li, Z. Zhang, C. Cao, M. Cai, S. Su, X. Sun, X. Shi, C. Li, T. Zhou, Y. Zhang, C. Chi, P. He, X. Xia, Y. Chen, S. S. Gambhir, Z. Cheng, J. Tian, Nat. Biomed. Eng. 2020, 4, 259; c) X. Meng, F. Yang, H. Dong, L. Dou, X. Zhang, Nano Today 2021, 38, 101156.
- 6Y. Yuan, S. Diao, X. Ni, D. Zhang, W. Yi, C. Jian, X. Hu, D. Li, A. Yu, W. Zhou, Q. Fan, J. Nanobiotechnol. 2022, 20, 44.
- 7X. Sang, T. Gao, X. Liu, Y. Shen, L. Chang, S. Fu, H. Yang, H. Yang, W. Mu, S. Liang, Z. Zhang, N. Zhang, Y. Liu, Adv. Sci. 2022, 9, 2201834.
- 8E. S. Hwang, P. Beitsch, P. Blumencranz, D. Carr, A. Chagpar, L. Clark, N. Dekhne, D. Dodge, D. L. Dyess, L. Gold, S. Grobmyer, K. Hunt, S. Karp, B.-A. Lesnikoski, I. Wapnir, B. L. Smith, I. s. team, JAMA Surgery 2022, 157, 573.
- 9Y. Qiu, Y. Zhang, M. Li, G. Chen, C. Fan, K. Cui, J.-B. Wan, A. Han, J. Ye, Z. Xiao, ACS Nano 2018, 12, 7974.
- 10a) M. Zhou, Q. Zuo, Y. Huang, L. Li, Acta Pharm. Sin. B 2022, 12, 3383; b) P. Sharma, S. Hu-Lieskovan, J. A. Wargo, A. Ribas, Cell 2017, 168, 707; c) M. Hu, J. Zhang, Y. Yu, K. Tu, T. Yang, Y. Wang, Q. Hu, L. Kong, Z. Zhang, Small 2020, 16, 2004905.
- 11a) L. N. M. Nguyen, Z. P. Lin, S. Sindhwani, P. MacMillan, S. M. Mladjenovic, B. Stordy, W. Ngo, W. C. W. Chan, Nat. Mater. 2023, 22, 1261; b) S. Sindhwani, A. M. Syed, J. Ngai, B. R. Kingston, L. Maiorino, J. Rothschild, P. MacMillan, Y. Zhang, N. U. Rajesh, T. Hoang, J. L. Y. Wu, S. Wilhelm, A. Zilman, S. Gadde, A. Sulaiman, B. Ouyang, Z. Lin, L. Wang, M. Egeblad, W. C. W. Chan, Nat. Mater. 2020, 19, 566.
- 12a) B. Chang, J. Chen, J. Bao, T. Sun, Z. Cheng, Chem. Rev. 2023, 123, 13966; b) J. Wang, Z. Sheng, J. Guo, H.-Y. Wang, X. Sun, Y. Liu, Coord. Chem. Rev. 2023, 486, 215137.
- 13a) Z. Xiang, J. Zhao, J. Qu, J. Song, L. Li, Angew. Chem., Int. Ed. 2022, 61, e202111836; b) X. Chai, Z. Fan, M.-M. Yu, J. Zhao, L. Li, Nano Lett. 2021, 21, 10047.
- 14a) Y. Chen, Y. Xing, Z. Wang, L. Li, H. Wang, S. Tang, K. Cai, J. Zhang, Biosens. Bioelectron. 2023, 223, 115026; b) R. Peng, X. Zheng, Y. Lyu, L. Xu, X. Zhang, G. Ke, Q. Liu, C. You, S. Huan, W. Tan, J. Am. Chem. Soc. 2018, 140, 9793.
- 15a) Z. Di, X. Lu, J. Zhao, A. Jaklenec, Y. Zhao, R. Langer, L. Li, Angew. Chem., Int. Ed. 2022, 61, e202205436; b) B. Liu, R. Ma, J. Zhao, Y. Zhao, L. Li, Sci. China: Chem. 2020, 63, 1490.
- 16a) S. Wu, Y. He, R. Zhou, C. Chen, D. Chen, H. Hu, Nano Today 2024, 54, 102049; b) J. G. Song, S. H. Lee, H.-K. Han, J. Nanobiotechnol. 2021, 19, 15; c) J. Debnath, N. Gammoh, K. M. Ryan, Nat. Rev. Mol. Cell Biol. 2023, 24, 560.
- 17a) T. Kang, J. S. Ni, T. Li, J. Wang, Z. Li, Y. Li, M. Zha, C. Zhang, X. Wu, H. Guo, L. Xi, K. Li, Biomaterials 2021, 275, 120907; b) T. Li, H. Guo, Y. Liu, W. Qi, C. Wu, L. Xi, Adv. Funct. Mater. 2022, 32, 2107624.
- 18Z. Wang, M. Zhan, W. Li, C. Chu, D. Xing, S. Lu, X. Hu, Angew. Chem., Int. Ed. 2021, 60, 4720.
- 19a) D. An, J. Fu, B. Zhang, N. Xie, G. Nie, H. Ågren, M. Qiu, H. Zhang, Adv. Funct. Mater. 2021, 31, 2101625; b) Y. Kang, N. Kong, M. Ou, Y. Wang, Q. Xiao, L. Mei, B. Liu, L. Chen, X. Zeng, X. Ji, Bioactive Materials 2023, 20, 663.
- 20a) X. Cui, Q. Ruan, X. Zhuo, X. Xia, J. Hu, R. Fu, Y. Li, J. Wang, H. Xu, Chem. Rev. 2023, 123, 6891; b) H. Kim, Y. Baek, T. Ha, D. Choi, W. J. Lee, Y. Cho, J. Park, S. Kim, J. Doh, Small 2023, 19, 2301377.
- 21K. Li, T.-H. Chang, Z. Li, H. Yang, F. Fu, T. Li, J. S. Ho, P.-Y. Chen, Adv. Energy Mater. 2019, 9, 1901687.
- 22a) Z. Huang, A. Alharbi, W. Mayer, E. Cuniberto, T. Taniguchi, K. Watanabe, J. Shabani, D. Shahrjerdi, Nat. Commun. 2020, 11, 3029; b) Y. Lin, Y. Wu, R. Wang, G. Tao, P.-F. Luo, X. Lin, G. Huang, J. Li, H.-H. Yang, Chem. Commun. 2018, 54, 8579.
- 23Y. Xing, L. Wang, L. Wang, J. Huang, S. Wang, X. Xie, J. Zhu, T. Ding, K. Cai, J. Zhang, Adv. Funct. Mater. 2022, 32, 2111171.
- 24Y. Xing, L. Li, Y. Chen, L. Wang, S. Tang, X. Xie, S. Wang, J. Huang, K. Cai, J. Zhang, ACS Nano 2023, 17, 6731.
- 25W. Nong, Y. Chen, D. Lv, Y. Yan, X. Zheng, X. Shi, Z. Xu, W. Guan, J. Wu, Y. Guan, Chem. Eng. J. 2022, 431, 134003.
- 26J. Zhang, J. Chen, J. Ren, W. Guo, X. Li, R. Chen, J. Chelora, X. Cui, Y. Wan, X.-J. Liang, Y. Hao, C.-S. Lee, Biomaterials 2018, 181, 92.
- 27J. Yu, X.-H. Wang, J. Feng, X. Meng, X. Bu, Y. Li, N. Zhang, P. Wang, Adv. Healthcare Mater. 2019, 8, 1900378.
- 28P. Kumar, F. Shahzad, S. Yu, S. M. Hong, Y.-H. Kim, C. M. Koo, Carbon 2015, 94, 494.
- 29X. Lu, H. Huang, X. Zhang, P. Lin, J. Huang, X. Sheng, L. Zhang, J.-p. Qu, Composites, Part B 2019, 177, 107372.
- 30Y. Deng, J. Li, T. Qian, W. Guan, Y. Li, X. Yin, Chem. Eng. J. 2016, 295, 427.
- 31F. Guo, J. Chen, J. Zhao, Z. Chen, D. Xia, Z. Zhan, Q. Wang, Chem. Eng. J. 2020, 386, 124014.
- 32a) Y. Cao, J.-H. Dou, N.-j. Zhao, S. Zhang, Y.-Q. Zheng, J.-P. Zhang, J.-Y. Wang, J. Pei, Y. Wang, Chem. Mater. 2017, 29, 718; b) J. Zhang, C. Yang, R. Zhang, R. Chen, Z. Zhang, W. Zhang, S.-H. Peng, X. Chen, G. Liu, C.-S. Hsu, C.-S. Lee, Adv. Funct. Mater. 2017, 27, 1605094.
- 33X. Yang, J. Zhu, D. Yang, J. Zhang, Y. Guo, X. Zhong, J. Kong, J. Gu, Composites, Part B 2020, 185, 107784.
- 34J. Yang, L.-S. Tang, R.-Y. Bao, L. Bai, Z.-Y. Liu, W. Yang, B.-H. Xie, M.-B. Yang, J. Mater. Chem. A 2016, 4, 18841.
- 35W. Yim, K. Takemura, J. Zhou, J. Zhou, Z. Jin, R. M. Borum, M. Xu, Y. Cheng, T. He, W. Penny, B. R. Miller III, J. V. Jokerst, ACS Nano 2022, 16, 683.
- 36a) Y. Song, X. Cai, G. Ostermeyer, S. Ding, D. Du, Y. Lin, Nanomicro Lett 2021, 13, 213. b) Y. Xia, J. Li, L. Wang, X. Luo, Y. Xie, Y. Liu, Angew. Chem. 2022, 61, e202115764.
- 37X. Wang, Q. Ding, R. R. Groleau, L. Wu, Y. Mao, F. Che, O. Kotova, E. M. Scanlan, S. E. Lewis, P. Li, B. Tang, T. D. James, T. Gunnlaugsson, Chem. Rev. 2024, 124, 7106.
- 38Y. Tang, Y. Li, X. Hu, H. Zhao, Y. Ji, L. Chen, W. Hu, W. Zhang, X. Li, X. Lu, W. Huang, Q. Fan, Adv. Mater. 2018, 30, 1801140.
