Bingbing Lin

Superparamagnetic iron oxide nanoparticles for MR imaging and therapy: design considerations and clinical applications.

Superparamagnetic iron oxide nanoparticles (SPION) based magnetic resonance imaging (MRI) is a powerful non-invasive tool in biomedical imaging, clinical diagnosis and therapy. In this review, the physicochemical properties of SPION and their in vivo performance were thoroughly discussed, also covering how surface engineering will prolong the circulation time and overcome biological barriers at organ, tissue, and cellular levels. Clinical applications and future potentials of SPION based MR imaging in cancer, cardiovascular, and inflammation diseases were addressed. Targeting mechanisms of SPION in both research and clinical use were summarized for better understanding of their performance. Addition of new targeting mechanisms to clinically approved SPION will bring opportunities to discover early diseases at cellular and molecular levels, and to track MRI-visible drug carriers. Clinical trial information related to SPION on Clinicaltrials.gov was summarized mainly based on their disease categories, therapeutic applications and clinical trial stages. It gives us a brief outlook of their clinical applications in the near future.

Delivery of siRNA by MRI-visible nanovehicles to overcome drug resistance in MCF-7/ADR human breast cancer cells

Multidrug resistance (MDR) is one of the major barriers in cancer chemotherapy. P-glycoprotein (P-gp), a cell membrane protein in MDR, also a member of ATP-Binding cassette (ABC) transporter, can increase the efflux of various hydrophobic anticancer drugs. In this study, polycation/iron oxide nanocomposites, were chosen as small interfering RNA (siRNA) carriers to overcome MDR through silencing of the target messenger RNA and subsequently reducing the expression of P-gp. Amphiphilic low molecular weight polyethylenimine was designed with different alkylation groups and alkylation degree to form various nanocarriers with clustered iron oxide nanoparticles inside and carrying siRNA through electrostatic interaction. A few optimized formulations can form stable nanocomplexes with siRNA and protect them from degradation during delivery, and lead to effective silencing effect that comparable to a commercial golden standard transfection agent, Lipofectamine 2000. Human breast cancer MCF-7/ADR cells can be vulnerable to doxorubicin treatment after the strong downregulation of P-gp through siRNA tranfection. Once transfected with these nanocomplexes, the cells displayed significant contrast enhancement against non-transfected cells under a 3T clinical MRI scanner. These nanocomposites also demonstrated their downregulation efficacy of P-gp in a MCF-7/ADR orthotopic tumor model in mice.

Theranostic Nanoparticles for Cancer and Cardiovascular Applications

Theranostics have received enormous attentions for individualized diagnosis and treatment in the past few years. Especially, the availability of various nanoplatforms provides great potentials for designing of sophisticated theranostic agents including imaging, targeting and therapeutic functions. Numerous reports have been published on how to construct multifunctional nanoparticles for the targeted diagnosis and therapy simultaneously since the concept of “theranostics”. This review presents recent advances of molecular imaging and nanoplatform technology, and their applications in drug discovery and development. Applications of nanoplatform-based theranostics in cancer and cardiovascular diseases will also be covered including diagnosis, assessment of drug biodistribution, and visualization of drug release from nanoparticles, as well as monitoring of therapeutic effects.

Reduction of polyethylenimine-coated iron oxide nanoparticles induced autophagy and cytotoxicity by lactosylation.

Superparamagnetic iron oxide (SPIO) nanoparticles are excellent magnetic resonance contrast agents and surface engineering can expand their applications. When covered with amphiphilic alkyl-polyethyleneimine (PEI), the modified SPIO nanoparticles can be used as MRI visible gene/drug delivery carriers and cell tracking probes. However, the positively charged amines of PEI can also cause cytotoxicity and restricts their further applications. In this study, we used lactose to modify amphiphilic low molecular weight polyethylenimine (C12-PEI2K) at different lactosylation degree. It was found that the N-alkyl-PEI-lactobionic acid wrapped SPIO nanocomposites show better cell viability without compromising their labelling efficacy as well as MR imaging capability in RAW 264.7 cells, comparing to the unsubstituted ones. Besides, we found the PEI induced cell autophagy can be reduced via lactose modification, indicating the increased cell viability might rely on down-regulating autophagy. Thus, our findings provide a new approach to overcome the toxicity of PEI wrapped SPIO nanocomposites by lactose modification.

Multivalent manganese complex decorated amphiphilic dextran micelles as sensitive MRI probes

T1 contrast agents based on Mn(II) were conjugated on amphiphilic dextran micelles via click chemistry. The obtained paramagnetic nanomicelle contrast agent has a higher T1 relaxivity (13.3 Mn mmol-1 s-1) and better sensitivity than those of free Mn(II) complexes. Studies carried out in vivo suggest that this contrast agent has a better and long-acting vascular enhancement effect at a lower manganese dosage (0.1 Mn mmol kg-1 BW).

Control of the interparticle spacing in superparamagnetic iron oxide nanoparticle clusters by surface ligand engineering

Polymer-mediated self-assembly of superparamagnetic iron oxide (SPIO) nanoparticles allows modulation of the structure of SPIO nanocrystal cluster and their magnetic properties. In this study, dopamine-functionalized polyesters (DA-polyester) were used to directly control the magnetic nanoparticle spacing and its effect on magnetic resonance relaxation properties of these clusters was investigated. Monodisperse SPIO nanocrystals with different surface coating materials (poly(e-caprolactone), poly(lactic acid)) of different molecular weights containing dopamine (DA) structure (DA-PCL2k, DA-PCL1k, DA-PLA1k)) were prepared via ligand exchange reaction, and these nanocrystals were encapsulated inside amphiphilic polymer micelles to modulate the SPIO nanocrystal interparticle spacing. Small-angle x-ray scattering (SAXS) was applied to quantify the interparticle spacing of SPIO clusters. The results demonstrated that the tailored magnetic nanoparticle clusters featured controllable interparticle spacing providing directly by the different surface coating of SPIO nanocrystals. Systematic modulation of SPIO nanocrystal interparticle spacing can regulate the saturation magnetization (M s) and T 2 relaxation of the aggregation, and lead to increased magnetic resonance (MR) relaxation properties with decreased interparticle spacing.