Purpose: Owing to the lack of effective biomarkers, triple-negative breast cancer (TNBC) has the worst prognosis among all subtypes of breast cancer. Meanwhile, tremendous progress has been made to identify biomarkers for TNBC. However, limited number of biomarkers still restrain the specifically targeting outcomes against TNBC. Here, to solve the obstacle, we designed and synthesized a new type of biocompatible nanoparticles to amplify the targeting effects for TNBC theranostics.
Methods: To identify the biomarker of TNBC, the expression of intercellular adhesion molecule-1 (ICAM1) was assessed by real-time polymerase chain reaction and western blot among all subtypes of breast cancer and normal breast epithelium. Then, vesicular nanoparticles based on poly(ethylene glycol)-poly(ϵ-caprolactone) copolymers were prepared by the double emulsion method and modified with anti-ICAM1 antibodies through click chemistry to conjugate with related antigens on TNBC cell membranes and then loaded with magnetic resonance imaging (MRI) contrast agent gadolinium and chemotherapeutic drug doxorubicin. The targeting capability, diagnostic and therapeutic efficacy of this nanoparticle were validated through cell-based and tumor model-based experiments.
Results: ICAM1 was expressed significantly higher on TNBC than on other subtypes of breast cancer and normal breast epithelium in both mRNA and protein level. Theranostic nanoparticle modified with anti-ICAM1 was proved to be able to specifically target to TNBC in vitro experiments. Such theranostic nanoparticle also displayed enhanced diagnostic and therapeutic efficacy by specifically targeting capability and extending circulation time in tumor models. The biocompatibility and biosafety of this nanoparticle was also confirmed in vitro and in vivo.
Conclusion: Overall, this new nanoparticle has been demonstrated with effective therapeutic outcomes against TNBC, providing a promising theranostic approach for MRI-guided therapy of TNBC.
Keywords: breast carcinoma, nanoparticles, magnetic resonance imaging, theranostics, intercellular adhesion molecule-1