Research Progress on Responsive Formulations for Cancer Prevention and Early Diagnosis
Main Article Content
Keywords
stimulus-responsive formulations, nanodelivery, cancer chemoprevention, precancerous lesions, early cancer diagnosis, theranostics
Abstract
Malignant tumors have become an urgent public health challenge worldwide. A wealth of clinical evidence indicates that intervening during the precancerous stage is the most cost-effective means of reducing the risk of cancer and improving patients’ long-term survival rates. Conventional cancer prevention formulations generally suffer from shortcomings such as insufficient targeting capability, short retention time at the lesion site, and low bioavailability in vivo. Furthermore, pharmacological prevention and lesion diagnosis are not integrated, making it difficult to meet the practical clinical needs for targeted intervention in precancerous lesions [6]. Stimulus-responsive (smart) formulations can recognize characteristic signals in the microenvironment of precancerous lesions and early-stage tumors, including pH changes, elevated levels of reactive oxygen species, elevated glutathione levels, high expression of specific proteases at the lesion site, and specific enzymes produced by gut microbiota. By responding to microenvironmental triggers to achieve localized, targeted drug release at the lesion site while simultaneously activating imaging signals, these formulations have opened up new avenues for early cancer prevention and early screening [16]. This article reviews the recent advances in stimulus-responsive formulations for cancer prevention and early diagnosis. It discusses targeted delivery systems for small-molecule chemopreventive agents, oral formulations responsive to the intestinal microenvironment, and mucosal delivery systems for the prevention and control of epithelial cancers. It also summarizes microenvironment-responsive imaging probes, biomarker-activated theranostic prodrugs, and nanosensor-based diagnostic technologies for body fluid samples, and introduces multifunctional nanoplatforms that combine preventive and diagnostic functions. Finally, it analyzes the practical challenges associated with biosafety, large-scale production, and clinical translation [4], and discusses future directions for the development of next-generation smart responsive formulations, with the aim of informing the development of novel formulations for cancer prevention and early diagnosis.
References
- [1]Amaolo, A., Scarciglia, A., Sorrentino, M., Di Gregorio, E., & Ferrauto, G. (2026). Breaking Through the Barrier: Nanoparticle-Driven MRI Strategies for Diagnosis and Therapy of Pancreatic Cancer. ACS Nanosci Au, 6(2), 166-183. doi:10.1021/acsnanoscienceau.5c00116
- [2]Bagde, A., Patel, K., Mondal, A., Kutlehria, S., Chowdhury, N., Gebeyehu, A., Patel, N., Kumar, N., Singh, M. (2019). Combination of UVB Absorbing Titanium Dioxide and Quercetin Nanogel for Skin Cancer Chemoprevention. AAPS PharmSciTech, 20(6), 240. doi:10.1208/s12249-019-1424-x
- [3]Bi, D., Yang, X., Wang, Y., Yong, J., Yang, F., Tan, X., Li, Y., Zheng, D., Li, P. (2026). Stimuli-responsive nanoplatforms for precision activation of the STING pathway in cancer immunotherapy. Frontiers in Immunology, 17, 1714249. doi:10.3389/fimmu.2026.1714249
- [4]Chao-hui, W., & Yu-lin, L. (2022). Progress and prospect in the clinical translation of cancer nanomedicine. Acta Pharmaceutica Sinica, 57(01), 134-141+277. doi:10.16438/j.0513-4870.2021-1259
- [5]Dong, Z., Li, S., Wei, Y., Zhao, J., Kong, W., Liu, W., Chen, J., He, H., Yang, J., Qi, J. (2026). Engineering oral commensal nanovaccines to activate mucosal-systemic immune cascades against tumor. Cell Host & Microbe, 34(9), 1729-1745.e1710. doi:10.1016/j.chom.2026.06.021
- [6]Hu, W., Ye, B., Yu, G., Huang, F., & Mao, Z. (2026). Stimuli-Responsive Supramolecular Biomaterials for Cancer Theranostics. Adv Sci (Weinh), 13(10), e15860. doi:10.1002/advs.202515860
- [7]Ke-liang, L., Yang, L., Chun-yang, L., Tian-le, H., Zhan-ying, H., Shan-chao, W., & Chun-quan, S. (2023). Recent advances in chemical fluorescent probes sensitive to tumormicroenyironments. Acta Pharmaceutica Sinica, 58(08), 2180-2192. doi:10.16438/j.0513-4870.2023-0590
- [8]Kim, M. S., Nam, I. H., Cha, H. J., & Jo, Y. K. (2025). Bandgap-engineered proteinic near-infrared nanodots for localized precision cancer theranostics. J Nanobiotechnology, 23(1), 541. doi:10.1186/s12951-025-03619-0
- [9]Koyande, N. P., Srivastava, R., Padmakumar, A., & Rengan, A. K. (2022). Advances in Nanotechnology for Cancer Immunoprevention and Immunotherapy: A Review. Vaccines (Basel), 10(10). doi:10.3390/vaccines10101727
- [10]Lee, J. M., Kang, S. J., Yoon, M. S., Jo, M. J., Yoo, M. K., Park, S. Y., Bong, S., Kim, J., Park, S., Lee, Y., Shin, Y., Lee, H. J., Kim, J. S., Park, C. W., Shin, D. H. (2026). Recent Advances in Nanoscale Sprayable Hydrogels for Cancer Management: Nanoparticle-Loaded Formulations for Therapy and Prevention. Int J Nanomedicine, 21, 558788. doi:10.2147/ijn.S558788
- [11]Lu, C., Xue, L., Luo, K., Liu, Y., Lai, J., Yao, X., Xue, Y., Huo, W., Meng, C., Xia, D., Gao, X., Yuan, Q., Cao, K. (2023). Colon-Accumulated Gold Nanoclusters Alleviate Intestinal Inflammation and Prevent Secondary Colorectal Carcinogenesis via Nrf2-Dependent Macrophage Reprogramming. ACS Nano, 17(18), 18421-18432. doi:10.1021/acsnano.3c06025
- [12]Lu, H., Lu, Q., Sun, H., Wang, Z., Shi, X., Ding, Y., Ran, X., Pei, J., Pan, Y., Zhang, Q. (2023). ROS-Responsive Fluorescent Sensor Array for Precise Diagnosis of Cancer via pH-Controlled Multicolor Gold Nanoclusters. ACS Appl Mater Interfaces, 15(32), 38381-38390. doi:10.1021/acsami.3c09320
- [13]Pan, W., Niu, H., Luo, S., Chen, L., & Wu, Z. S. (2024). Intelligent Reconfiguration-Promoted Cellular Internalization of Core-Shell DNA Nanoprobe Equipped with Successive Dual Stimuli-Responsive Protective Satellites for Amplification Fluorescence Imaging of Tumor Cells. Small, 20(28), e2311388. doi:10.1002/smll.202311388
- [14]Pattni, B. S., Chupin, V. V., & Torchilin, V. P. (2015). New Developments in Liposomal Drug Delivery. Chemical Reviews, 115(19), 10938-10966. doi:10.1021/acs.chemrev.5b00046
- [15]Song, K., Ren, L., Guo, X., Ren, G., Sun, Y., Tian, X., Hu, C., Pan, M., Yu, Q., Luo, Z., Hao, Y., Lei, P., Yu, H., Yang, S., Chen, Q., Li, Y., Wang, S., He, Y., Hui, Z., Zheng, W., Jiang, J., Wang, L. (2025). Microbiota-responsive oral nano-amifostine enables colorectal-specific radioprotection and tumor immunity via gut microenvironment reprogramming. Adv Compos Hybrid Mater, 8(6), 432. doi:10.1007/s42114-025-01492-x
- [16]Wang, Q., Guo, Z., Chen, Z., Wang, C., Yang, Y., Shi, Q., Gao, Q., Li, H., Zhang, D., Liu, Y., Liu, Y. (2026). pH-Responsive Materials for Therapy and Precision Biomedical Imaging. Chem Biomed Imaging, 4(6), 1018-1042. doi:10.1021/cbmi.5c00279
- [17]Wen-xiu, Q., Han, C., Xian-zheng, Z., & Ren-xi, Z. (2018). Research on Stimulus-Responsive Peptides and Their Applications in Cancer Diagnosis and Treatment. Acta polymerica sinica(01), 32-44.
- [18]Xiao-feng, L. (2019). Research Advances on Tumor MicroenvironmentResponsive Nano-Preparations. Progress in pharmaceutical sciences, 43(11), 865-875.
- [19]Xiao-lin, H., & Jian-ping, Z. (2025). The Application Progress of Tumor Microenvironment-Responsive NanoDrug Delivery System in Tumor Therapy. Shandong Chemical Industry, 54(12), 104-107. doi:10.19319/j.cnki.issn.1008-021x.2025.12.033
- [20]Xu, X. (2024). Design of Stimuli-responsive Hybrid Polymer Nanogels for Tumor Theranostics. (Master’s thesis), Donghua University, Available from Cnki
- [21]Xu, Y., Zhao, Z., Kong, Y., Fan, Y., He, J., Fan, Z., Wang, G., Hu, Y. (2026). Host-Guest Assembly of Transmucosal Molecular Spherical Nucleic Acids for Oral Leukoplakia Immunotherapy and Microbiota Homeostasis Restoration. JACS Au, 6(3), 1927-1944. doi:10.1021/jacsau.6c00012
- [22]Yu, C., Xia, H., Wang, Y., & Liu, X. (2025). Smart nanoplatforms for early detection and immune modulation in lung cancer. Front Bioeng Biotechnol, 13, 1734570. doi:10.3389/fbioe.2025.1734570
- [23]Yu, Z., Shao-ping, Y., Jia-nan, X., & Juan, L. (2018). Research Advances in Tumor Microenvironment Responsive Polymeric Nano-drug Delivery System. Progress in pharmaceutical sciences, 42(05), 366-374.
- [24]Zhao, C., Hou, D., Wang, K., Chen, J., Wu, Y., Liu, N., Wang, Z., Liu, Y., Li, Y., Zhang, Z., Liu, Y., Hou, Z., Yang, X., Liu, X., Xu, W., Wang, Z., Zhang, H., Liu, Z. (2026). Mucoadhesive tumor-penetrating nanomedicine for intravesical chemo-immunotherapy against bladder cancer. Sci Adv, 12(16), eaeb9764. doi:10.1126/sciadv.aeb9764
- [25]Zhao, X., Zhao, R., & Liu, P. (2025). pH/ROS Dual-Responsive Self-Amplified ROS-Replenishing Self-Delivery Systems for Tumor-Specific Chemotherapy/Ferroptosis. Bioconjugate Chemistry, 36(12), 2599-2607. doi:10.1021/acs.bioconjchem.5c00422
- [26]Zhuo-ran, L., Jie, Z., & Zhi-jie, W. (2025). Applications of artifcial intelligence in the feld of tumor markers research. Electronic Journal of Comprehensive Cancer Treatment, 11(01), 26-35.
- [27]Zi-ang, W., Sheng-nan, H., Yi-jing, L., Wei-wei, Z., Meng-jie, Z., Yun-long, Z., & Xia-li, Z. (2024). Research Progress of Enzyme-Responsive Tumor TargetingNano-Formulations. China Cancer, 33(09), 769-780.
