- 作者: Yi-Fan Chen, Yen-Hsin Wang, Cing-Syuan Lei, Chun A. Changou, Mark E. Davis and Yun Yen
- 作者服務機構: 1. The Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, 11031, Taipei, Taiwan 2. Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, Taipei Medical University, 11031, Taipei, Taiwan 3. TMU Research Center of Cancer Translational Medicine, Taipei Medical University, 11031, Taipei, Taiwan 4. Ph.D. Program of Cancer Biology and Drug Discovery, Taipei Medical University, 11031, Taipei, Taiwan 5. Integrated Laboratory, Center of Translational Medicine, Taipei Medical University, 11031, Taipei, Taiwan 6. Core Facility, Taipei Medical University, 11031, Taipei, Taiwan 7. Chemical Engineering, California Institute of Technology, Pasadena, CA, 91125, USA 8. TMU Research Center of Cancer Translational Medicine, Taipei Medical University, 11031, Taipei, Taiwan 9. Graduate Institute of Cancer Biology and Drug Discovery, Taipei Medical University, 11031, Taipei, Taiwan 10. Cancer Center, Taipei Municipal WanFang Hospital, 11696, Taipei, Taiwan
- 中文摘要:
- 英文摘要:
Introduction
Efficacy and safety are critical concerns when designing drug carriers. Nanoparticles are a particular type of carrier that has gained recent attention in cancer therapeutics.
Methods
In this study, we assess the safety profile of IT-101, a nanoparticle formed by self-assembly of camptothecin (CPT) conjugated cyclodextrin-based polymers. IT-101 delivers CPT to target cancer cells in animal models of numerous human cancers and in humans. Previous data from preclinical and clinical trials indicate that IT-101 has no notable immunological side effects. However, there have been no published studies focused on evaluating the effects of IT-101 on host immune systems.
Results
In this work, we demonstrate that IT-101 diminished initial host immune response following first injection of the nanopharmaceutical and induced NK cell activation and T cell proliferation upon further IT-101 exposure. Additionally, IT-101 could attenuate tumor growth more efficiently than CPT treatment only.
Conclusions
Drugs administration in whole-body circulation may lead to poorly bioavailable in central nervous system and often has toxic effects on peripheral tissues. Conjugated with cyclodextrin-based polymers not only reduce adverse effects but also modulate the immune responses to elevate drug efficacy. These immune responses may potentially facilitate actions of immune blockage, such as PD1/PDL1 in cancer treatment. - 中文關鍵字:
- 英文關鍵字: Nanoparticle, Camptothecin, Immune responses, Brain tumor