Qinghua Xie,Xuemei Wang,Gaorui Zhang,Dawei Zhou,Yuxuan Zhao,Hong Liu,Jiazhi Duan,Dexin Yu,Yuanhua Sang
Individual theranostic agents with dual-mode MRI responses and therapeutic efficacy have attracted extensive interest due to the real-time monitor and high effective treatment, which endow the providential treatment and avoid the repeated medication with side effects. However, it is difficult to achieve the integrated strategy of MRI and therapeutic drug due to complicated synthesis route, low efficiency and potential biosafety issues. In this study, novel self-assembled ultrasmall Fe 3 O 4 nanoclusters were developed for tumor-targeted dual-mode T 1 /T 2 -weighted magnetic resonance imaging (MRI) guided synergetic chemodynamic therapy (CDT) and chemotherapy. The self-assembled ultrasmall Fe 3 O 4 nanoclusters synthesized by facilely modifying ultrasmall Fe 3 O 4 nanoparticles with 2,3-dimercaptosuccinic acid (DMSA) molecule possess long-term stability and mass production ability. The proposed ultrasmall Fe 3 O 4 nanoclusters shows excellent dual-mode T 1 and T 2 MRI capacities as well as favorable CDT ability due to the appropriate size effect and the abundant Fe ion on the surface of ultrasmall Fe 3 O 4 nanoclusters. After conjugation with the tumor targeting ligand Arg-Gly-Asp (RGD) and chemotherapy drug doxorubicin (Dox), the functionalized Fe 3 O 4 nanoclusters achieve enhanced tumor accumulation and retention effects and synergetic CDT and chemotherapy function, which serve as a powerful integrated theranostic platform for cancer treatment.
Precise delivery of antineoplastic drugs to specific tumor region has drawn much attention in recent years. Herein, a light/magnetic hyperthermia triggered drug delivery with multiple functionality is designed based on methotrexate (MTX) modified thermo-sensitive magnetoliposomes (MTX-MagTSLs). In this system, MTX and oleic acid modified magnetic nanoparticles (MNPs) can be applied in biological and magnetic targeting. Meanwhile, lipophilic fluorescent dye Cy5.5 and MNPs are encapsulated into the bilayer of liposomes , which can not only achieve dual-imaging effect to verify the MTX-MagTSLs accumulation in tumor region, but also provide an appropriate laser irradiation region to release Doxorubicin (Dox) under alternating magnetic field (AMF). Both in vitro and in vivo results revealed that MTX-MagTSLs possessed an excellent targeting ability towards HeLa cells and HeLa tumor-bearing mice. Furthermore, the heating effect of MTX-MagTSLs was amplified 4.2-fold upon combination with AMF and local precise near-infrared laser irradiation (808 nm) (DUAL-mode) to rapidly reach the phase change temperature (Tm) of MTX-MagTSLs in 5 min compared with either AMF or laser stimulation alone, resulting in a significantly enhanced release of Dox at tumor region and precise cancer synergetic theranostics.