Theranostics of Triple-Negative Breast Cancer Based on Conjugated Polymer Nanoparticles

• Published in: ACS applied materials & interfaces Vol. 10; no. 13; pp. 10634 - 10646
• Main Authors: Jin, Guorui, He, Rongyan, Liu, Qian, Dong, Yuqing, Lin, Min, Li, Wenfang, Xu, Feng
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 04.04.2018
• Subjects: Animals; Cell Line, Tumor; Humans; Mice; Nanoparticles; Polymers; Theranostic Nanomedicine; Triple Negative Breast Neoplasms; theranostics; tumor imaging; triple-negative breast cancer therapy; conjugated polymer; photodynamic therapy
• ISSN: 1944-8244; 1944-8252
• DOI: 10.1021/acsami.7b14603

Triple-negative breast cancer (TNBC) does not respond to many targeted drugs due to the lack of three receptors (i.e., estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2), which makes it difficult for TNBC detection and treatment. As compared to traditional breast cancer treatments such as surgery and chemotherapy, photodynamic therapy (PDT) has emerged as a promising approach for treating TNBC due to its precise controllability, high spatiotemporal accuracy, and minimal invasive nature. However, traditional photosensitizers used in PDT are associated with limitations of aggregation-caused quenching (ACQ), and the ACQ induced a significant decrease in reactive oxygen species (ROS) generation. To address these, we synthesized a cyclic arginine-glycine-aspartic acid (cRGD) peptide-decorated conjugated polymer (CP) nanoparticles with poly­[2-methoxy-5-(2-ethyl-hexyloxy)-1,4-phenylenevinylene] (MEH-PPV) as the photosensitizer for the theranostics of TNBC. The synthesized CP nanoparticles show bright fluorescence with high stability and could effectively produce ROS under light irradiation. Cell viability studies showed that the CP nanoparticles have negligible dark cytotoxicity and could efficiently kill the αvβ3 integrin-overexpressed MDA-MB-231 cells (one subtype of TNBC cells) in a selective way. With the use of cRGD-modified MEH-PPV nanoparticles as the theranostic agent, it permits targeted imaging and PDT of TNBC both in the in vitro 3D tumor model and in living mice. The application of CP nanoparticles in the successful theranostics of TNBC could pave the way for future development of CP-based photosensitizers for clinical applications.