Multimodal imaging of nano-assembled microspheres loaded with doxorubicin and Cisplatin for liver tumor therapy

Abstract

Currently, clinically available drug-loaded embolic microspheres have some shortcomings, such as being invisible with standard medical imaging modalities and only being able to carry positively charged drugs. The visualization of drug-loaded microspheres is very important for real-time monitoring of embolic position to improve the therapeutic effect. Meanwhile, the visualization of microspheres can enable postoperative reexamination, which is helpful for evaluating the embolization area and guiding the subsequent treatment. In addition, microspheres capable of loading different charged drugs can increase the choice of chemotherapeutic drugs and provide more possibilities for treatment. Therefore, it is of great importance to explore drug-loaded microspheres capable of multimodal imaging and loading drugs with different charges for transarterial chemoembolization (TACE) treatment of liver tumors. In our study, we designed a kind of nano-assembled microspheres (NAMs) that can realize computer X-ray tomography (CT)/magnetic resonance imaging (MRI)/Raman multimodal imaging, be loaded with positively and negatively charged drugs and test their imaging ability, drug loading and biological safety. The microspheres have strong attenuation performance for CT, high T2 relaxation for MRI and good sensitivity for surface enhanced Raman spectroscopy (SERS). At the same time, our microspheres can also load the positively charged drug, doxorubicin (DOX), and negatively charged drug Cisplatin. One gram of NAMs can hold 168 mg DOX or 126 mg Cisplatin, which has good drug loading and sustained-release capacity. Cell experiments also showed that the nano-assembled microspheres had good biocompatibility. Therefore, as multimodal developed drug loaded microspheres, nano assembled microspheres have great potential in TACE treatment of liver cancer.

Fabrication of polymeric microspheres for biomedical applications

“…288 Recently, studies have focused on fabricating microspheres capable of multi-modal imaging such as X-ray, computed tomography (CT), magnetic resonance imaging (MRI) and surface-enhanced Raman spectroscopy, which can realize real-time visualization and allow accurate tracking of the embolic agents. 301 In recent years, researchers have attempted to develop multifunctional embolic microspheres which integrate the functions of drug loading, CT/MR dual-modality imaging, and photothermal together (Fig. 15b).…”

Interventional radiological therapies in colorectal hepatic metastases

“…DEB-TACE has certain limitations including (i) inability to identify the beads in real-time which in turn prevents the visualization of intraoperative precise delivery and post-operative effects (ii) as the DEBs load only positively charged chemotherapeutic medications, the options of drugs are restricted ( 139 ). Hence, new drug carriers are being studied to overcome the limitations.…”

pH‐Triggered Transformable Peptide Nanocarriers Extend Drug Retention for Breast Cancer Combination Therapy

“…In addition, Pep1 can self‐assemble in N ‐(2‐hydroxyethyl)piperazine‐29‐(2‐ethane‐sulfonic acid) (HEPES) solution to form spherical NPs, the antitumor drug DDP can be encapsulated in Pep1 by forming favorable carboxyl–drug interactions, and the differentiation‐promoting drug ATRA can be encapsulated in a hydrophobic core due to its lipid solubility. [ 35–38 ] Our designed drug‐loaded NPs transform into aggregates that contain sheet‐like structures at pH 5, and this morphological change effectively prolongs the retention of DDP and ATRA at the tumor site. ATRA can reverse the CSC phenotype, alleviate the aggregation of CSCs caused by long‐term DDP administration, and inhibit tumor growth and metastasis.…”