A novel bone marrow targeted gadofullerene agent protect against oxidative injury in chemotherapy

Abstract

Chemotherapy as an effective cancer treatment technique has been widely used in tumor therapy. However, it is still a challenge to overcome the serious side effects of chemotherapy, especially for its myelotoxicity. Here we report a novel strategy using the water soluble gadofullerene nanocrystals (GFNCs) to protect against chemotherapy injury in hepatocarcinoma bearing mice, which was induced by the commonly chemotherapeutic agent cyclophosphamide (CTX). The GFNCs were revealed to specifically accumulate in the bone marrow after intravenously injecting to mice and they exhibited excellent radical scavenging function, resulting in a prominent increase of mice blood cells and pathological improvements of the primary organs in the GFNCs (15 mg kg ) therapy. Moreover, the GFNCs maintained and even strengthened the antineoplastic activity of the CTX agent. Therefore, the GFNCs would be the promising chemoprotective agents in chemotherapy based on their high efficiency, low toxicity and metabolizable property.

The potential biomedical platforms based on the functionalized Gd@C82 nanomaterials

“…The results demonstrated that the levels of those indicators tended to normal levels in healthy mice after treatment 19,36,46,60 . Interestingly, instead of inducing significant pathological injuries of main organs like the liver, spleen, kidneys, and bones of mice, Gd@C 82 nanomaterials reverse the damage of these organs induced by radiation or chemotherapeutic agents 15,17 . All these results indicated that functionalized Gd@C 82 nanomaterials exhibit excellent biosafety, laying the foundation for their further biomedical or clinical application.…”

“…blood cells and pathological improvements of the primary organs (Figure 5A,B). 15 As is known that the cisplatin (CP) is a cornerstone of the chemotherapeutic regimens, but acquired resistance confines its application. As shown in Figure 5C, CP exhibited high inhibiting effects on CP‐sensitive tumors, but hardly worked on CP‐resistant tumors.…”

“…Generally, there are two commonly used methods to detect the contents of Gd@C 82 nanomaterials, one is inductively coupled plasma mass spectrometry (ICP), another is radiolabeling. After intravenous injection, Gd@C 82 nanomaterials mainly accumulated in the liver, spleen, lungs, bone, and so on 15,46,47 . Importantly, the biodistribution was different in Gd@C 82 nanomaterials with different functional groups modification.…”

“…After modified by functional groups of hydroxy, carboxyl, amino groups, and so on, Gd@C 82 exhibited high potential in biomedicine, such as magnetic resonance imaging (MRI) contrast, antitumor therapeutics, adjuvant therapeutic agents, metabolic diseases modulation, and so forth (Figure 1). 10–20 In this review, we briefly summarize the recent progresses achieved in these potential biomedical applications of the functionalized Gd@C 82 nanomaterials.…”

Real-time monitoring of tumor vascular disruption induced by radiofrequency assisted gadofullerene

“…Briefly, the gadofullerene based nanomaterials were modified with hydroxyl groups on the surface of carbon cage to form the water soluble GFNCs [23,24]. When performing the tumor therapy, the GFNCs solution was intravenously injected to the testing tumor-bearing mice, and partial of the GFNCs particles would reach the tumor blood vessels along with the blood flow and try to penetrate out through the vascular leaks.…”