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Targeting the organelle for radiosensitization in Cancer radiotherapy

Asian Journal of Pharmaceutical Sciences 2024年第2期19卷 52-71页

作者： Xiaoyan Sun Linjie Wu Lina Du Wenhong Xu Min Han Institute of Pharmaceutics College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Department of Pharmaceutical Sciences Beijing Institute of Radiation MedicineBeijing 100850China Department of Radiation Oncology Key Laboratory of Cancer Prevention and InterventionThe Second Afliated HospitalCollege of MedicineZhejiang UniversityHangzhou 310058China Hangzhou Institute of Innovative Medicine Zhejiang UniversityHangzhou 310058China Jinhua Institute of Zhejiang University Jinhua 321299China National Key Laboratory of Advanced Drug Delivery and Release Systems Zhejiang UniversityHangzhou 310058China

radiotherapy is a well-established cytotoxic therapy for local solid cancers, utilizing high-energy ionizing radiation to destroy cancer cells. However, this method has several limitations, including low radiation energy deposition, severe damage to surrounding normal cells, and high tumor resistance to radiation. Among various radiotherapy methods, boron neutron capture therapy (BNCT) has emerged as a principal approach to improve the therapeutic ratio of malignancies and reduce lethality to surrounding normal tissue, but it remains deficient in terms of insufficient boron accumulation as well as short retention time, which limits the curative effect. Recently, a series of radiosensitizers that can selectively accumulate in specific organelles of cancer cells have been developed to precisely target radiotherapy, thereby reducing side effects of normal tissue damage, overcoming radioresistance, and improving radiosensitivity. In this review, we mainly focus on the field of nanomedicine-based Cancer radiotherapy and discuss the organelle-targeted radiosensitizers, specifically including nucleus, mitochondria, endoplasmic reticulum and lysosomes. Furthermore, the organelle-targeted boron carriers used in BNCT are particularly presented. Through demonstrating recent developments in organelle-targeted radiosensitization, we hope to provide insight into the design of organelle-targeted radiosensitizers for clinical cancer treatment.

关键词： Cancer radiotherapy Organelle-target Radiosensitization Boron neutron capture therapy Nanomedicines

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Selectively enhancing radiosensitivity of cancer cells via in situ enzyme-instructed peptide self-assembly

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Acta Pharmaceutica Sinica B 2020年第12期10卷 2374-2383页

作者： Yang Gao Jie Gao Ganen Mu Yumin Zhang Fan Huang Wenxue Zhang Chunhua Ren Cuihong Yang Jianfeng Liu Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine Institute of Radiation MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300192China Radiation Oncology Department Tianjin Medical University General HospitalTianjin 300052China

The radiotherapy modulators used in clinic have disadvantages of high toxicity and low selectivity.For the first time,we used the in situ enzyme-instructed self-assembly(EISA)of a peptide derivative(Nap-GDFDFpYSV)to selectively enhance the sensitivity of cancer cells with high alkaline phosphatase(ALP)expression to ionizing radiation(IR).Compared with the in vitro pre-assembled control formed by the same molecule,assemblies formed by in situ EISA in cells greatly sensitized the ALPhigh-expressing cancer cells to y-rays,with a remarkable sensitizer enhancement ratio.Our results indicated that the enhancement was a result of fixing DNA damage,arresting cell cycles and inducing cell apoptosis.Interestingly,in vitro pre-formed assemblies mainly localized in the lysosomes after incubating with cells,while the assemblies formed via in situ EISA scattered in the cell cytosol.The accumulation of these molecules in cells could not be inhibited by endocytosis inhibitors.We believed that this molecule entered cancer cells by diffusion and then in situ self-assembled to form nanofibers under the catalysis of endogenous ALP.This study provides a successful example to utilize intracellular in situ EISA of small molecules to develop selective tumor radiosensitizers.

关键词： In situ enzyme-instructed self-assembly(EISA) Pre-assembly Alkaline phosphatase(ALP) Peptide Cancer radiotherapy Nanofiber Histone deacetylases inhibitor(HDACI) Radiosensitizer

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