Abstract
BackgroundOwing to high genetic diversities of tumor cells and low response rate of standard chemotherapy, patients with triple negative breast cancer (TNBC) have short progression-free survivals and poor outcomes, which need to explore an effective approach to improve therapeutic efficacy.MethodsNovel gadolinium doped carbon dots (Gd@CDs) have been designed and prepared through hydrothermal method with 3,4-dihydroxyhydrocinnamic acid, 2,2′-(ethylenedioxy)bis(ethylamine) and gadolinium chloride. The synthesized nanostructures were characterized. Taking advantage of good biocompatibility of Gd@CDs, a nanoplatform based on Gd@CDs has been developed to co-deliver chemotherapy drug doxorubicin hydrochloride (Dox) and a near-infrared (NIR) photothermal agent, IR825 for magnetic resonance imaging (MRI) guided photothermal chemotherapy for TNBC.ResultsThe as-synthesized Dox@IR825@Gd@CDs displayed favorable MRI ability in vivo. Upon NIR laser irradiation, Dox@IR825@Gd@CDs could convert the NIR light to heat and efficiently inhibit tumor growth through photothermal chemotherapy in vitro and in vivo. Additionally, the impact of photothermal chemotherapy on the murine motor coordination was assessed by rotarod test. Dox@IR825@Gd@CDs presented low toxicity and high photothermal chemotherapy efficiency.ConclusionA noble theranostic nanoplatform (Dox@IR825@Gd@CDs) was developed that could be tailored to achieve loading of Dox and IR825, intracellular delivery, favorable MRI, excellent combination therapy with photothermal therapy and chemotherapy to enhance therapeutic effect against TNBC cells. This study will provide a promising strategy for the development of Gd-based nanomaterials for MRI and combinational therapy for TNBC.Graphic abstract
Highlights
Owing to high genetic diversities of tumor cells and low response rate of standard chemotherapy, patients with triple negative breast cancer (TNBC) have short progression-free survivals and poor outcomes, which need to explore an effective approach to improve therapeutic efficacy
Preparation and characterization of gadolinium doped carbon dots (Gd@carbon dots (CDs)) Gd@CDs were prepared via the typical solvent-thermal method, in which dihydroxyhydrocinnamic acid (DHCA) and anhydrous Anhydrous gadolinium chloride (GdCl3) were used as the carbon source and Magnetic resonance imaging (MRI) contrast agent, while EDA was as a passivation agent
Comparing with the 1H Nuclear magnetic resonance (NMR) spectra of EDA and DHCA, the chemical shifts of Gd@CDs at 1.39–4.39 ppm were assigned to the protons on saturated carbons and the appearing signals in the range of 6.24 and 7.03 ppm were attributed to the protons on the amine groups (Fig. 1a)
Summary
Owing to high genetic diversities of tumor cells and low response rate of standard chemotherapy, patients with triple negative breast cancer (TNBC) have short progression-free survivals and poor outcomes, which need to explore an effective approach to improve therapeutic efficacy. Since free Gd3+ ions are toxic in vivo, the potential Gd retention within the skin, bones, and solid organs may cause a high toxicity profile by calcium antagonist, nephrogenic systemic fibrosis (NSF) in patients with impaired renal function [7,8,9,10]. To address these questions, new generation of Gd-containing nanoprobes, including Gd2O3 nanoparticles, Gd-loaded silica nanoparticles, Gd-doped Fe3O4 nanoparticles and Gd-encapsulated carbon dots (CDs), have been developed to suppress the side-effect caused by the Gd leakage [11]. Gd-encapsulated CDs have been recognized as smart candidates as MRI probes and drug carriers for cancer therapy
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