Application value of manganese-loaded caramelized carbonaceous nanospheres for synchronized breast cancer MRI and photothermal therapy / 中华放射学杂志

ABSTRACT

Objective To investigate the application value of pH sensitive manganese-loaded caramelized carbonaceous nanospheres (Mn-CNS) in the synchronous MRI and photothermal therapy for breast cancer. Methods Anhydrous glucose was used as carbon source to prepare caramelized carbonaceous nanospheres(CNS).Mn2 +was absorbed and bonded to its surface to obtain the Mn-CNS.The MR signal values of aqueous solutions of Mn-CNS under different pH(pH=7.4,6.0,5.0)with different Mn2+concentrations(0,0.14,0.28,0.57,1.14 and 2.28 mmol/L)were measured to obtain the relaxation rate.The cell counting kit-8(CCK-8)assay was used to determine the effect of Mn-CNS on the viability of 4T1 cells. Pathological examination was used to evaluate the systemic toxicity. Inductively coupled plasma mass spectrometry (ICP-MS) was used to analyze Mn uptake by different cell lines (human breast cancer cells MCF-7, human normal mammary epithelial cells MCF-10A and human macrophages cells). The 4T1 tumor-bearing BALB/c mice were divided randomly into four groups (6 mice per group) (1) normal saline (intratumoral injection)plus near infrared laser(NIR);(2)normal saline(intravenous injection)plus NIR;(3) Mn-CNS(intratumoral injection)plus NIR;(4)Mn-CNS(intravenous injection)plus NIR.After intratumoral injection for 30 min and intravenous injection for 12 h,the tumors were continuously irradiated with 808 nm laser for 10 min,the temperature changes and relative tumor volume were recorded.The MRI was obtained at different time point(pre-injection and post-injection at 15 min,30 min,1 h,4 h,8 h,12 h,24 h,48 h,4 d, respectively)with the dose of Mn-CNS(4 mg Mn/kg)by intravenous injection.The changes of Mn2+content before and after Mn-CNS incubation and the tumor volume differences among each group were compared by t test.Results The values of r1were 0.18 L·mmol-1·s-1(pH 5.0),3.48 L·mmol-1·s-1(pH 6.0)and 5.42 L· mmol- 1·s- 1(pH 7.4), respectively. The cells viability of 4T1 were all above 90 % when the cells were incubated with Mn-CNS at different concentrations (25, 50, 100 and 200 μg/ml). MCF-7 and human macrophages cells were ingested Mn2+.The Mn2+amount before and after uptake were significant difference(P<0.05).The MCF-10A had a slight uptake of Mn2+which was not statistically significant(P>0.05).After 10 minutes of the laser exposure (2 w/cm2), the change of temperature with tumor among different groups were shown as followMn-CNS(intratumoral injection)>Mn-CNS(intravenous injection)>normal saline(intravenous injection)>normal saline (intratumoral injection). After photothermal therapy, the relative tumor volumes of Mn-CNS (intratumoral injection)and normal saline(intratumoral injection)were statistically different(t=-2.724,P<0.05). Meanwhile,the relative tumor volumes also showsd significant difference among Mn-CNS(intravenous injection) and normal saline (inject intravenous injection) groups (t=-5.193,P<0.05). After intravenous injection of Mn-CNS in 4T1 tumor-bearing mice, the signal intensity of T1gradually increased and reached the peak of enhancement at 4 h after which the signal intensity remained stable and decreased slightly at 12 h,then gradually decreased to normal. The T1signal intensity of kidney was consistent with that of the tumor and higher. Meanwhile, the degree of liver tissue enhancement was the lowest. Conclusions Mn-CNS is highly biocompatible and self-degradable,it can targeted MRI and achieve precise photothermal therapy simultaneously, which is of great value in the integrated diagnosis and treatment of breast cancer.