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

Abstract

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 αβ 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.

Conjugated polymers as nanoparticle probes for fluorescence and photoacoustic imaging

“…Moreover, CPNs containing pDA encapsulated in a PEGylated phospholipid shell with average size of < 6 nm, enabled rapid in vivo fluorescence imaging of blood flow in mice (Table 2 and Figure 5B) 91 . Despite their lack of near infrared absorption, CPNs of MEH-PPV were investigated as a theranostic agent against TNBC 20 (Figure 5A). In this study, MEH-PPV encapsulated into DSPE-PEG2000 and functionalised with cyclic arginine-glycine-aspartic acid (cRGD) peptide was selectively taken up by αvβ3 integrin-overexpressed MDA-MB-231 TNBC cell line and induced cell death in vitro, both in 2D and 3D MDA-MB-231 models, after laser illumination 20 .…”

“…The fact that they are organic materials has also boosted the interest in their biological application, which has been evidenced in the recent efforts to produce biodegradable conjugated polymers 14,15 . Besides being used for bioimaging, CPNs have also been studied as drug delivery systems 12 , including photoresponsive drug release 16 , biosensors 17 and as theranostic agents for cancer treatments [18][19][20] . In this review, we discuss the role of conjugated polymers in the bioimaging field, focusing on their formulation into nanoparticles and their early safety screening.…”

Current Targets and Bioconjugation Strategies in Photodynamic Diagnosis and Therapy of Cancer

“…This bioconjugate was able to specifically identify MDA-MB-231 tumors in mice models in vivo, allowing for PDD of TNBC. In addition, the bioconjugate was able to be activated and destroy the MDA-MB-231 tumor and inhibit growth [139]. This bioconjugate thus has potential to be used for both PDT and PDD in the future and could closely guide tumor removal.…”

Combination Therapy and Nanoparticulate Systems: Smart Approaches for the Effective Treatment of Breast Cancer

“…Researchers have explored PBNP not only for drug loading but also for theranostic purposes. Jin and co-workers conjugated luminescent poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene] with the cyclic arginine-glycine-aspartic acid conjugated polymer nanoparticles, which generates reactive oxygen species (ROS) when irradiated with light and has shown promising results on MDA-MB-231 cells [ 143 ]. Nuannuan Li and co-workers synthesized pH-sensitive self-assembling amphiphilic copolymers formulated into polymersomes by incorporating verapamil hydrochloride and doxorubicin hydrochloride, to overcome doxorubicin resistance in the MCF-7/ARD cell line [ 144 ].…”