polyethyleneimine-coated-iron-oxide-nanoparticles-as-vehicle-for

Polyethyleneimine-coated Iron Oxide Nanoparticles as a Vehicle for the Delivery of Small Interfering RNA to Macrophages <em>In Vitro</em> and <em>In Vivo</em>

Because of their critical role in regulating immune responses, macrophages have continuously been the subject of intensive research and represent a ...

Southeast University

Developing an ultrasensitive and high-efficient molecular imaging probe for detection of malignant tumors is extremely needed in clinical and remains a big challenge. Here, we report a novel bispecific nanoprobe for dual-targeted T2-weighed magnetic resonance imaging (MRI) of COLO-205 colorectal cancer in vivo. First, the magnetic iron oxide nanoparticles (FeO@OA) were synthesized by a thermal decomposition method. Then, PEGylation of the hydrophobic FeO@OA was implemented by amphiphilic DSPE-PEG2000-COOH, producing water-soluble nanoparticles (FeO@PEG). Lastly, arginine-glycine-asparticacid-tumornecrosis factor-related apoptosis-inducing ligand (RGD-TRAIL), a bispecific fusion protein, was conjugated with the nanoparticle to construct molecularly multi-targeted nanoprobe, which was defined as FeO@RGD-TRAIL. This FeO@RGD-TRAIL was proven to exhibit extremely high relaxation property (r=534mMs) and saturation magnetization value (M=92 emu/g Fe). In vitro studies showed its dual-targeting combination capacity, favorable biocompatibility and strong ability to resist against the non-specific phagocytosis. Owing to these excellent advantages, high sensitive and efficient imaging of tumor was achieved in vivo. Therefore, this RGD-TRAIL conjugated nanoprobe could be developed as a multi-targeted contrast enhancement agent for magnetic resonance molecular imaging in detection of cancer.

Improving sensitivity of magnetic resonance imaging by using a dual-targeted magnetic iron oxide nanoprobe.

Micelle drugs based on a polymeric platform offer great advantages over liposomal drugs for tumor treatment. Although nearly all of the nanomedicines approved in the clinical use can passively target to the tumor tissues on the basis of an enhanced permeability and retention (EPR) effect, the nanodrugs have shown heterogenous responses in the patients. This phenomenon may be traced back to the EPR effect of tumor, which is extremely variable in the individuals from extensive studies. Nevertheless, there is a lack of experimental data describing the EPR effect and predicting its impact on therapeutic efficacy of nanoagents. Herein, we developed 32 nm magnetic iron oxide nanoparticles (MION) as a T-weighted contrast agent to describe the EPR effect of each tumor by in vivo magnetic resonance imaging (MRI). The MION were synthesized by a thermal decomposition method and modified with DSPE-PEG2000 for biological applications. The PEGylated MION (FeO@PEG) exhibited high r of 571 mM s and saturation magnetization (M) of 94 emu g Fe as well as long stability and favorable biocompatibility through the in vitro studies. The enhancement intensities of the tumor tissue from the MR images were quantitatively measured as TNR (Tumor/Normal tissue signal Ratio) values, which were correlated with the delay of tumor growth after intravenous administration of the PLA-PEG/PTX micelle drug. The results demonstrated that the group with the smallest TNR values (TNR < 0.5) displayed the best tumor inhibitory effect. In addition, there was a superior correlation between TNR value and relative tumor delay in individual mice. These analysis results indicated that the TNR value of the tumor region enhanced by FeO@PEG (d = 32 nm) could be used to predict the therapeutic efficacy of the micelle drugs (d ≤ 32 nm) in a certain period of time. FeO@PEG has a potential to serve as an ideal MRI contrast agent to visualize the EPR effect in patients for accurate medication guidance of micelle drugs in the future treatment of tumors.

Using PEGylated magnetic nanoparticles to describe the EPR effect in tumor for predicting therapeutic efficacy of micelle drugs.

Locoregional recurrence of breast cancer after tumor resection represents several clinical challenges. Here, we demonstrate that co-delivery of chemotherapy and thermotherapeutic agents by a magnetic supramolecular hydrogel (MSH) following tumor resection prevents tumor recurrence in a breast cancer mouse model. The self-assembled MSH was designed through the partial inclusion complexation associated with the threading of α-CD on the copolymer moieties on the surface of the PEGylated iron oxide (FeO) nanoparticles, which enables shear-thinning injection and controllable thermoreversible gel-sol transition. MSH was injected to the postoperative wound uniformly, which became mobile and perfect match with irregular cavity without blind angle due to the magnetocaloric gel-sol transition when exposed to alternating current magnetic field (ACMF). The magnetic nanoparticle-mediated induction heat during the gel-sol transition process caused the triggered release of dual-encapsulated chemotherapeutic drugs and provided an effect of thermally induced cell damage. The hierarchical structure of the MSH ensured that both hydrophobic and hydrophilic drugs can be loaded and consecutively delivered with different release curves. The hydrogel nanocomposite might provide a potential locally therapeutic approach for the precise treatment of locoregional recurrence of cancer.

Article	Year
Improving sensitivity of magnetic resonance imaging by using a dual-targeted magnetic iron oxide nanoprobe. Colloids and surfaces. B, Biointerfaces\| PubMed ID: 29100127	2018
Using PEGylated magnetic nanoparticles to describe the EPR effect in tumor for predicting therapeutic efficacy of micelle drugs. Nanoscale\| PubMed ID: 29308812	2018
Injectable magnetic supramolecular hydrogel with magnetocaloric liquid-conformal property prevents post-operative recurrence in a breast cancer model. Acta biomaterialia\| PubMed ID: 29729897	2018

Haoan Wu

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