Ternary-Responsive Drug Delivery with Activatable Dual Mode Contrast-Enhanced in Vivo Imaging

Abstract

Designing a smart nanotheranostic system has recently attracted tremendous attention and is highly desirable for realizing targeted cancer therapy and early diagnosis. Herein we report the fabrication of smart nanotheranostic system using multiresponsive gatekeeping protocol of mesoporous silica nanoparticles (MSN). Acid, oxidative stress and redox sensitive manganese oxide (MnO ) coated superparamagnetic iron oxide nanoparticle (SPION) were employed as nanolids to regulate the camptothecin drug release from the channels of mesoporous silica and achieve responsive dual-mode MRI contrast. The nonvehicle showed high magnetization and T2 contrast in magnetic resonance imaging (MRI) due to the significant density of SPION onto the surface of MSN, and at the same time the MnO shell degradation release Mn which enhanced the T1MRI visualization. The efficacy of responsive drug delivery system was investigated on pancreatic cancer cells and tumor-bearing mice, and results reinforced that MnO -SPION@MSN@CPT nonvehicle is efficacious against cancer cells. We envision that our unique and multiresponsive nanoplatform may find applications in effective delivering of imaging and therapeutic agents to wide range of diseases besides cancer.

Self-generating oxygen enhanced mitochondrion-targeted photodynamic therapy for tumor treatment with hypoxia scavenging

“…Manganese oxide nanocrystals (Mn 3 O 4 nanoparticles), which serve as gatekeepers, block the hydrophobic photosensitizer IR780-loaded channels of MSNs. H 2 O 2 is one of the tumor metabolites (present at high amounts, up to 1 mM), and Mn 3 O 4 nanoparticles in this study act as an efficient catalyst to continually break down H 2 O 2 to oxygen without external activation 30-32. Moreover, the H 2 O 2 -responsive disintegration of Mn 3 O 4 nanoparticles leads to oxygen generation and switch opening.…”

<p>Manganese Oxide Nanoparticles As MRI Contrast Agents In Tumor Multimodal Imaging And Therapy</p>

“…Additionally, the relaxation time of the nanoprobe was approximately 10 times lower than that of the crystalline particles 127. Ren and colleagues used MnO x coated superparamagnetic iron oxide nanoparticles as gates to control the CPT release from mesoporous silica and so achieve the TME-responsive T1/T2 dual-mode MRI-guided pancreatic cancer chemotherapy both in vitro and in vivo 128. Similarly, Gao and colleagues labeled technetium-99 ( 99m Tc) on the surface of the MnO x -based mesoporous silica nanoparticles (MnO x -MSN) to integrate SPECT and MRI imaging modalities for both excellent sensitivity and high spatial resolution 129.…”

New Advances in In Vivo Applications of Gated Mesoporous Silica as Drug Delivery Nanocarriers

“…Ren et al designed a nanotheranostic system based on manganese oxide (MnO x ) coated superparamagnetic iron oxide nanoparticles (SPION) and MSNs loaded with camptothecin (CPT) . The SPION nanoparticles were covered with a thin layer of MnO x and finally modified with carboxylic acid groups.…”