Trever Todd

RGD Modified Apoferritin Nanoparticles for Efficient Drug Delivery to Tumors

Ferritin (FRT) is a major iron storage protein found in humans and most living organisms. Each ferritin is composed of 24 subunits, which self-assemble to form a cage-like nanostructure. FRT nanocages can be genetically modified to present a peptide sequence on the surface. Recently, we demonstrated that Cys-Asp-Cys-Arg-Gly-Asp-Cys-Phe-Cys (RGD4C)-modified ferritin can efficiently home to tumors through RGD-integrin αvβ3 interaction. Though promising, studies on evaluating surface modified ferritin nanocages as drug delivery vehicles have seldom been reported. Herein, we showed that after being precomplexed with Cu(II), doxorubicin can be loaded onto RGD modified apoferritin nanocages with high efficiency (up to 73.49 wt %). When studied on U87MG subcutaneous tumor models, these doxorubicin-loaded ferritin nanocages showed a longer circulation half-life, higher tumor uptake, better tumor growth inhibition, and less cardiotoxicity than free doxorubicin. Such a technology might be extended to load a broad range of therapeutics and holds great potential in clinical translation.

Tumor Vasculature Targeted Photodynamic Therapy for Enhanced Delivery of Nanoparticles

Delivery of nanoparticle drugs to tumors relies heavily on the enhanced permeability and retention (EPR) effect. While many consider the effect to be equally effective on all tumors, it varies drastically among the tumors’ origins, stages, and organs, owing much to differences in vessel leakiness. Suboptimal EPR effect represents a major problem in the translation of nanomedicine to the clinic. In the present study, we introduce a photodynamic therapy (PDT)-based EPR enhancement technology. The method uses RGD-modified ferritin (RFRT) as “smart” carriers that site-specifically deliver 1O2 to the tumor endothelium. The photodynamic stimulus can cause permeabilized tumor vessels that facilitate extravasation of nanoparticles at the sites. The method has proven to be safe, selective, and effective. Increased tumor uptake was observed with a wide range of nanoparticles by as much as 20.08-fold. It is expected that the methodology can find wide applications in the area of nanomedicine.

Gd-encapsulated carbonaceous dots with efficient renal clearance for magnetic resonance imaging.

Nanoprobes for MRI and optical imaging are demonstrated. Gd@C-dots possess strong fluorescence and can effectively enhance signals on T1 -weighted MR images. The nanoprobes have low toxicity, and, despite a relatively large size, can be efficiently excreted by renal clearance from the host after systemic injection.

Iron oxide nanoparticle encapsulated diatoms for magnetic delivery of small molecules to tumors.

Small molecules can be co-loaded with iron oxide nanoparticles onto diatoms. With an external magnetic field, the diatoms, after systemic administration, can be attracted to tumors. This study suggests a great potential of diatoms as a novel and powerful therapeutic vehicle.

Fe5C2 Nanoparticles with High MRI Contrast Enhancement for Tumor Imaging

An ancient material for magnetic resonance (MR) imaging: For the first time, Fe5C2 is prepared as colloidal stable nanoparticles with good aqueous stability. The nanoparticles boast strong magnetization, excellent chemical inertness, low toxicity, and one of the highest r2 relaxivities reported to date. These nanoparticles hold great potential in MR imaging as well as in other biomedical areas.

Ferritins as nanoplatforms for imaging and drug delivery.

Introduction: Due to unique architecture and surface properties, ferritin has emerged as an important class of biomaterial. Many studies suggest that ferritin and its derivatives hold great potential in a wide range of bio-applications. Areas covered: In this review, we summarize recent progress on employing ferritins as a platform to construct functional nanoparticles for applications in MRI, optical imaging, cell tracking, and drug delivery. Expert opinion: As a natural polymer, ferritins afford advantages such as high biocompatibility, good biodegradability, and a relatively long plasma half-life. These attributes put ferritins ahead of conventional materials in clinical translation for imaging and drug delivery purposes.

LiF@SiO 2 nanocapsules for controlled lithium release and osteoarthritis treatment

Electrolytes can be taken orally or intravenously as supplements or therapeutics. However, their therapeutic window may exceed the serum toxicity threshold, making systemic delivery a poor option. Local injection is also not adequate due to rapid diffusion of electrolytes. Here, we solved this issue with a nanocapsule technology, comprising an electrolyte nanocrystal as the drug filling and a silica sheath to regulate drug release rates. In particular, we prepared LiF@SiO2 nanocapsules and investigated their potential as a delivery system for lithium, which was shown in recent studies to be an effective therapeutic agent for osteoarthritis (OA). We demonstrated that LiF@SiO2 can extend lithium release time from minutes to more than 60 h. After intraarticular (i.a.) injection into a rat OA model, the nanocapsules reduced the Osteoarthritis Research Society International (OARSI) score by 71% in 8 weeks while inducing no systemic toxicity. Our study opens new doors for improved delivery of electrolyte therapeutics, which have rarely been studied in the past.

Protein-Adsorbed Magnetic-Nanoparticle-Mediated Assay for Rapid Detection of Bacterial Antibiotic Resistance

Antibiotic susceptibility tests have been used for years as a crucial diagnostic tool against antibiotic-resistant bacteria. However, due to a lack of biomarkers specific to resistant types, these approaches are often time-consuming, inaccurate, and inflexible in drug selections. Here, we present a novel susceptibility test method named protein-adsorbed nanoparticle-mediated matrix-assisted laser desorption-ionization mass spectrometry, or PANMS. Briefly, we adsorb five different proteins (β-casein, α-lactalbumin, human serum albumin, fibrinogen, and avidin) onto the surface of Fe3O4. Upon interaction with bacteria surface, proteins were displaced from the nanoparticle surface, the amounts of which were quantified by matrix-assisted laser desorption ionization mass spectrometry. We find that the protein displacement profile was different distinctive among different bacteria strains and, in particular, between wild-type and drug-resistant strains. More excitingly, we observe bacteria resistant to drugs of the same mechanisms share similar displacement profiles on a linear discriminant analysis (LDA) map. This suggests the possibility of using PANMS to identify the type of mechanism behind antibiotic resistance, which was confirmed in a blind test. Given that PANMS is free of drug incubation and the whole procedure takes less than 50 min, it holds great potential as a high-throughput, low-cost, and accurate drug susceptibility test in the clinic.