Focusing on Novel Biomaterials: Dedicated to the R&D and Implementation of Medical Imaging Probes and Drug Delivery Systems

Professor MA Kai is committed to the basic research and translational implementation of novel biomaterials. Integrating cutting-edge technologies and concepts in materials chemistry and bioengineering, he addresses the pain points of traditional technologies and unmet clinical needs to develop clinically translatable novel medical imaging probes and drug delivery systems, providing new ideas and approaches for disease diagnosis and treatment.

Targeting the shortcomings of traditional drug delivery technologies, he has developed innovative and differentiated drug delivery platforms based on a novel silsesquioxane sol-gel chemical system. Leveraging the functional diversity and biocompatibility of silsesquioxane biomaterials, these platforms overcome the limitations of traditional drug delivery systems in aspects such as drug loading capacity, tissue permeability, extrahepatic delivery efficiency, biological barrier penetration, formulation stability, biodistribution, and delivery precision. They enable large-capacity and precise in vivo delivery of small-molecule drugs, peptides, nucleic acids, antibody fragments, therapeutic and diagnostic radionuclides, and fluorescent dyes.

Aiming at the drawbacks of conventional diagnostic and therapeutic methods, he has explored innovative applications of novel biomaterial platforms in the diagnosis and treatment of major diseases through unique modular orthogonal conjugation technology. These applications include PET/MRI dual-modal contrast agents, nucleic acid delivery, nuclear medicine molecular diagnosis and targeted therapy, imaging and treatment of central nervous system diseases and brain tumors, fluorescence image-guided lymph node dissection and tumor resection, and targeted drug delivery for solid tumors and hematological malignancies.

Furthermore, utilizing the platform-based advantages of the technology, he integrates medical imaging probes and drug delivery systems within the same biomaterial platform framework to facilitate integrated diagnosis and treatment precision medicine. Focusing on diseases with significant unmet clinical needs, he prioritizes clinical translation and technological implementation. Multiple medical imaging probes and drug delivery systems based on novel biomaterials have been advanced into Phase I and II human clinical trials, with dozens of patents successfully translated into practical applications.

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).

Academic Honors and Awards

## 2025

- **Asia-Pacific Biomedical Engineering Consortium (APBEC) Young Scholar Award**

- **Bayer Research Translation Fund** (拜耳科研转化基金)

## 2020

- Selected as a recipient of the **National High-Level Overseas Talent Introduction Plan (Youth Program)** (中国国家海外高层次人才引进计划青年项目)

## 2016

- **Cornell University Excellence in Doctoral Research Award** (美国康奈尔大学卓越博士生研究奖)

## 2013

- Awarded the **National Science Foundation (NSF) Young Investigator Award** (美国国家自然科学基金资助青年科学家)

## 2012

- **Cornell University Distinguished Teaching Assistant** (美国康奈尔大学杰出助教)

Patent Technology

As of 2022, Professor Ma has obtained over 30 authorized invention patents at home and abroad, with 24 patents successfully commercialized. Below are selected patents:

1. **Functionalized nanoparticles and methods of making and using same** (US11419952B2), K. Ma, U. Wiesner

2. **Ultrasmall nanoparticles and methods of making and using same** (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** (US11246946B2), M. Bradbury, U. Wiesner, M. Overholtzer, H. Scher, K. Ma

4. **Nanoparticle drug conjugates** (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** (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** (US10732115), U. Wiesner, K. Ma

7. **Nanoparticle immunoconjugates** (US20180133342A1), B. Yoo, T. Quinn, M. Bradbury, U. Wiesner, J. Lewis, K. Ma, Feng Chen