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马恺

探索生物材料前沿技术,为疾病的诊断和治疗提供新手段

E-mail: kaima@tsinghua.edu.cn

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聚焦新型生物材料,专注医学影像探针和药物递送系统的研发和落地

马恺教授专注于新型生物材料的基础研究和转化落地,结合材料化学和生物工程领域的前沿技术和理念,针对传统技术的痛点和临床未被满足的需求,研发可临床转化的新型医学影像探针和药物递送系统,为疾病的诊断和治疗提供新思路和新手段。

针对传统药物递送技术的缺陷,利用新型硅氧体溶胶凝胶化学体系,研发创新型差异化药物递送平台,通过硅氧体生物材料的功能多样性和生物相容性,突破传统药物递送系统在药物装载量,组织渗透率,肝外递送效率,生物屏障穿越,制剂稳定性,生物分布,递送精准度等方面的不足,实现对小分子药物,多肽分子,核酸,抗体片段,诊疗核素,和荧光染料分子的大容量精准体内递送。并针对传统诊疗手段的痛点,利用独特的模块化正交偶联技术,开发新型生物材料平台在重大疾病诊断和治疗中的创新应用,包括PET/MRI靶向造影剂,核酸递送,核医学分子诊断和靶向治疗,中枢神经系统疾病和脑部肿瘤的成像和治疗,荧光影像指导的淋巴清扫术和肿瘤切除手术,实体肿瘤和血液肿瘤的靶向药物递送等。进一步利用技术的平台化优势,在同一生物材料平台框架下,将医学影像探针和药物递送系统相结合,以助力实现诊疗一体化精准医疗。针对存在重大临床未被满足需求的疾病,聚焦临床转化和技术落地,已将多项基于新型生物材料的医学影像探针和药物递送系统推进进入I,II期人体临床试验,数十项专利已被成果转化。

1. F. Wu, P. M. Chen, T. C. Gardinier, M. Z. Turker, A. M. Venkatesan, V. Patel, T. Khor, M. S. Bradbury, U. B. Wiesner, G. P. Adams, G. Germano, F. Chen*, and K. Ma*, Ultrasmall Folate Receptor Alpha Targeted Enzymatically Cleavable Silica Nanoparticle Drug Conjugates Augment Penetration and Therapeutic Efficacy in Models of Cancer,ACS Nano16, 20021-20033 (2022).

2. T. Aubert#, K. Ma#, K. Tan, U. Wiesner*, Two-Dimensional Superstructures of Silica Cages,Advanced Materials32, 1908362 (2020).

3. F. Chen#, B. Madajewski#, K. Ma#, D. K. Zanoni, H. Stambuk, M. Pauliah, M. Z. Turker, S. Monette, L. Zhang, B. Yoo, P. Chen, R. J. C. Meester, S. D. Jonge, T. P. Quinn, M. Gonen, S. Sequeira, E. D. Stanchina, J. D. Wolchok, P. Zanzonico, U. Wiesner*, S. G. Patel*, M. S. Bradbury*, Molecular Phenotyping and Image-Guided Surgical Treatment of Melanoma Using Spectrally-distinct Ultrasmall Core-Shell Silica Nanoparticles,Science Advances, 5, 12 (2019), doi:10.1126/sciadv.aax5208.

4. K. Ma, Y. Gong, T. Aubert, M. Turker, T. Kao, P. Doerschuk, U. Wiesner*, Surfactant Micelle Self-assembly Directed Highly Symmetric Ultrasmall Inorganic Cages,Nature558, 577–580 (2018).

5. F. Chen#, K. Ma#, B. Madajewski, L. Zhuang, L. Zhang, K. Rickert, M. Marelli, B. Yoo, M. Turker, M. Overholtzer, T. Quinn, M. Gonen, P. Zanzonico, A. Tuesca, M. Bowen, L. Norton, J. Subramony, U. Wiesner*, M. Bradbury*, Ultrasmall Targeted Nanoparticles with Engineered Antibody Fragments for Imaging Detection of HER2-overexpressing Breast Cancer,Nature Communications9, 4141 (2018).

6. K. Ma, K. A. Spoth, Y. Cong, D. Zhang, T. Aubert, M. Z. Turker, L. F. Kourkoutis, E. Mendes, U. Wiesner*, Early Formation Pathways of Surfactant Micelle Directed Ultrasmall Silica Ring and Cage Structures,J. Am. Chem. Soc.140, 17343–17348 (2018).

7. Y. Sun#, K. Ma#, T. Kao#, K. A. Spoth, H. Sai, D. Zhang, L. F. Kourkoutis, V. Elser, U. Wiesner*, Formation Pathways of Mesoporous Silica Nanoparticles with Dodecagonal Tiling,Nature Communications8, 252 (2017).

8. S. E. Kim, L. Zhang, K. Ma, M. Riegman, F. Chen, I. Ingold, M. Conrad, M. Z. Turker, M. Gao, X. Jiang, S. Monette, M. Pauliah, M. Gonen, P. Zanzonico, T. Quinn, U. Wiesner, M. S. Bradbury*, M. Overholtzer*, Ultrasmall Nanoparticles Induce Ferroptosis in Nutrient-Deprived Cancer Cells and Suppress Tumour Growth,Nature Nanotechnology11, 977–985 (2016).

2020 中国国家海外高层次人才引进计划青年项目入选者

2016 美国康奈尔大学卓越博士生研究奖

2013 美国国家自然科学基金资助青年科学家

2012 美国康奈尔大学杰出助教


专利技术

截至2022年,马恺教授获得国内外已授权发明专利30余项,其中24项已成果转化,部分专利列举如下:

1. Functionalized nanoparticles and methods of making and using same, United States Patent US11419952B2, K. Ma, U. Wiesner

2. Ultrasmall nanoparticles and methods of making and using same, United States Patent US11291737B2, U. Wiesner, K. Ma, C. Mendoza

3. Methods of treatment using ultrasmall nanoparticles to induce cell death of nutrient-deprived cancer cells via ferroptosis, United States Patent US11246946B2, M. Bradbury, U. Wiesner, M. Overholtzer, H. Scher, K. Ma

4. Nanoparticle drug conjugates, Chinese Patent CN106659797B, B. Yoo, M. Bradbury, U. Wiesner, K. Ma

5. Cyclic peptides with enhanced nerve-binding selectivity, nanoparticles bound with said cyclic peptides, and use of same for real-time in vivo nerve tissue imaging, United States Patent US10940216, M. Bradbury, B. Yoo, U. Wiesner, P. Chen, K. Ma, S. Patel, D. K. Zanoni

6. Mesoporous oxide nanoparticles and methods of making and using same, United States Patent US10732115, U. Wiesner, K. Ma

7. Nanoparticle immunoconjugates, United States Patent US20180133342A1, B. Yoo, T. Quinn, M. Bradbury, U. Wiesner, J. Lewis, K. Ma, Feng Chen