Targeting triple‐negative breast cancer with an aptamer‐functionalized nanoformulation: a synergistic treatment that combines photodynamic and bioreductive therapies

Journal of Nanobiotechnology

Jyun-Wei Wen¹  Yi-Te Chou¹  Ying-Feng Chang¹  Ja-an Annie Ho²  Ling-Chun Hung³  Li-chen Wu⁴  Chih-Yu Lin⁵  Chia-Min Yang⁶ 

[1] BioAnalytical Chemistry and Nanobiomedicine Laboratory, Department of Biochemical Science and Technology, National Taiwan University, 10617, Taipei, Taiwan;BioAnalytical Chemistry and Nanobiomedicine Laboratory, Department of Biochemical Science and Technology, National Taiwan University, 10617, Taipei, Taiwan;Center for Biotechnology, National Taiwan University, 10617, Taipei, Taiwan;Department of Chemistry, National Taiwan University, 10617, Taipei, Taiwan;BioAnalytical Chemistry and Nanobiomedicine Laboratory, Department of Biochemical Science and Technology, National Taiwan University, 10617, Taipei, Taiwan;NTU Instrumentation Center, Technology Commons, College of Life Science, National Taiwan University, 10617, Taipei, Taiwan;Department of Applied Chemistry, National Chi Nan University, 54561, Puli, Nantou, Taiwan;Department of Chemistry, National Tsing Hua University, 30013, Hsinchu, Taiwan;Department of Chemistry, National Tsing Hua University, 30013, Hsinchu, Taiwan;Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, 30013, Hsinchu, Taiwan;

关键词: Triple‐negative breast cancer;    Photodynamic therapy;    Tumor hypoxia;    Bioreductive prodrug;    Hollow mesoporous silica nanoparticle;    DNA aptamer;   

DOI  :  10.1186/s12951-021-00786-8

来源: Springer

【 摘 要 】

BackgroundAreas of hypoxia are often found in triple-negative breast cancer (TNBC), it is thus more difficult to treat than other types of breast cancer, and may require combination therapies. A new strategy that combined bioreductive therapy with photodynamic therapy (PDT) was developed herein to improve the efficacy of cancer treatment. Our design utilized the characteristics of protoporphyrin IX (PpIX) molecules that reacted and consumed O2 at the tumor site, which led to the production of cytotoxic reactive oxygen species (ROS). The low microenvironmental oxygen levels enabled activation of a bioreductive prodrug, tirapazamine (TPZ), to become a toxic radical. The TPZ radical not only eradicated hypoxic tumor cells, but it also promoted therapeutic efficacy of PDT.ResultsTo achieve the co-delivery of PpIX and TPZ for advanced breast cancer therapy, thin-shell hollow mesoporous Ia3d silica nanoparticles, designated as MMT-2, was employed herein. This nanocarrier designed to target the human breast cancer cell MDA-MB-231 was functionalized with PpIX and DNA aptamer (LXL-1), and loaded with TPZ, resulting in the formation of TPZ@LXL-1-PpIX-MMT-2 nanoVector. A series of studies confirmed that our nanoVectors (TPZ@LXL-1-PpIX-MMT-2) facilitated in vitro and in vivo targeting, and significantly reduced tumor volume in a xenograft mouse model. Histological analysis also revealed that this nanoVector killed tumor cells in hypoxic regions efficiently.ConclusionsTaken together, the synergism and efficacy of this new therapeutic design was confirmed. Therefore, we concluded that this new therapeutic strategy, which exploited a complementary combination of PpIX and TPZ, functioned well in both normoxia and hypoxia, and is a promising medical procedure for effective treatment of TNBC.

【 授权许可】

CC BY