Targeting cancer cells through Mn(II)-dpa grafted silica nanoparticles

The unique properties of paramagnetic nanoscale metal-organic frameworks provide them with high potential as key probes and vectors in the next generation of biomedical applications. To increase the nanoparticle targeting at the tumor site, the grafting of Mn(II)-dpa (dpa =di(picolyl)amines) on oxide nanoparticles (SiO₂) is proposed. The new Mn(II)-dpa-grafted silica nanoparticles can enhance the MR imaging area in cancer tissues and perturb the Ca²⁺-loaded mitochondria swelling. Experimental results indicate the cancer cells may be targeted through possible intracellular Ca²⁺ signaling mitochondria accumulating in vivo.     

Photochemical mineralization of europium, titanium, and iron oxyhydroxide nanoparticles in the ferritin protein cage

The Fe storage protein ferritin was used as a size-constrained reaction vessel for the photoreduction and reoxidation of complexed Eu, Fe, and Ti precursors for the formation of oxyhydroxide nanoparticles. The resultant materials were characterized by dynamic light scattering, gel electrophoresis, UV-vis spectroscopy, and transmission electron microscopy. The photoreduction and reoxidation process is inspired by biological sequestration mechanisms observed in some marine siderophore systems.     

Targeting of cancer cells using click-functionalized polymer capsules

Targeted delivery of drugs to specific cells allows a high therapeutic dose to be delivered to the target site with minimal harmful side effects. Combining targeting molecules with nanoengineered drug carriers, such as polymer capsules, micelles and polymersomes, has significant potential to improve the therapeutic delivery and index of a range of drugs. We present a general approach for functionalization of low-fouling, nanoengineered polymer capsules with antibodies using click chemistry. We demonstrate that antibody (Ab)-functionalized capsules specifically bind to colorectal cancer cells even when the target cells constitute less than 0.1% of the total cell population. This precise targeting offers promise for drug delivery applications.     

Magnetic response of mitochondria-targeted cancer cells with bacterial magnetic nanoparticles

We first demonstrate the effects of magnetic trapping of mitochondria using aptamer conjugated to bacterial magnetic nanoparticles that allowed targeting of the mitochondrial cytochrome c in the treatment of cancer cells. Our findings offer a new approach for targeted cell therapy, with the advantage of remote control over subcellular elements.     

Selective imaging and killing of cancer cells with protein-activated near-infrared fluorescing nanoparticles

We present a general approach for the selective imaging and killing of cancer cells using protein-activated near-infrared emitting and cytotoxic oxygen generating nanoparticles. Poly(propargyl acrylate) (PA) particles were surface modified through the copper-catalyzed azide/alkyne cycloaddition of azide-terminated indocyanine green (azICG), a near-infrared emitter, and poly(ethylene glycol) (azPEG) chains of various molecular weights. The placement of azICG onto the surface of the particles allowed for the chromophores to complex with bovine serum albumin when dispersed in PBS that resulted in an enhancement of the dye emission. In addition, the inclusion of azPEG with the chromophores onto the particle surface resulted in a synergistic ninefold enhancement of the fluorescence intensity, with azPEGs of increasing molecular weight amplifying the response. Human liver carcinoma cells (HepG2) overexpress albumin proteins and could be employed to activate the fluorescence of the nanoparticles. Preliminary PDT studies with HepG2 cells combined with the modified particles indicated that a minor exposure of 780 nm radiation resulted in a statistically significant reduction in cell growth.     

Characterization and surface reactivity of ferrihydrite nanoparticles assembled in ferritin

Ferrihydrite nanoparticles with nominal sizes of 3 and 6 nm were assembled within ferritin, an iron storage protein. The crystallinity and structure of the nanoparticles (after removal of the protein shell) were evaluated by high-resolution transmission electron microscopy (HRTEM), atomic force microscopy (AFM), and scanning tunneling microscopy (STM). HRTEM showed that amorphous and crystalline nanoparticles were copresent, and the degree of crystallinity improved with increasing size of the particles. The dominant phase of the crystalline nanoparticles was ferrihydrite. Morphology and electronic structure of the nanoparticles were characterized by AFM and STM. Scanning tunneling spectroscopy (STS) measurements suggested that the band gap associated with the 6 nm particles was larger than the band gap associated with the 3 nm particles. Interaction of SO2(g) with the nanoparticles was investigated by attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, and results were interpreted with the aid of molecular orbital/density functional theory (MO/DFT) frequency calculations. Reaction of SO2(g) with the nanoparticles resulted primarily in SO(3)2- surface species. The concentration of SO3(2-) appeared to be dependent on the ferrihydrite particle size (or differences in structural properties).     

Targeting and photodynamic killing of a microbial pathogen using protein cage architectures functionalized with a photosensitizer

The selectivity of antimicrobial photodynamic therapy (PDT) can be enhanced by coupling the photosensitizer (PS) to a targeting ligand. Nanoplatforms provide a medium for designing delivery vehicles that incorporate both functional attributes. We report here the photodynamic inactivation of a pathogenic bacterium, Staphylococcus aureus, using targeted nanoplatforms conjugated to a photosensitizer (PS). Both electrostatic and complementary biological interactions were used to mediate targeting. Genetic constructs of a protein cage architecture allowed site-specific chemical functionalization with the PS and facilitated dual functionalization with the PS and the targeting ligand. These results demonstrate that protein cage architectures can serve as versatile templates for engineering nanoplatforms for targeted antimicrobial PDT.     

Iron and cobalt oxide and metallic nanoparticles prepared from ferritin

Metallic Fe and Co and Fe- and Co-based oxide nanoparticles were prepared by a novel method utilizing the biologically relevant protein ferritin. In particular, iron and cobalt oxyhydroxide nanoparticles were assembled within horse spleen and Listeria innocua derived ferritin, respectively, in the aqueous phase. Ferritin containing either Fe or Co oxide was transferred and dried on a SiO2 support where the protein shell was removed during exposure to a highly oxidizing environment. It was also shown that the metal oxide particles could be reduced to the respective metal by heating in hydrogen. X-ray photoelectron spectroscopy was used to characterize the composition of the particles and atomic force microscopy was used to characterize the size of the nanoparticles. Depending on the Fe or Co loading and/or type of ferritin used, metallic and oxide nanoparticles could be produced within a range of 20-60 A.     

Magnetic–fluorescent Langmuir–Blodgett films of fluorophore-labeled ferritin nanoparticles

We have covalently coupled fluorophore 4-(2-hydroxyethoxy)-7-nitro-2,1,3-benzoxadiazole (NBD) to the external ferritin shell through lysine residues. An increase in the luminescence quantum yield of the fluorescent ferritin particles and a blue shift in its emission peak compared to individual fluorophore were observed. The study of the particles by transmission electron microscopy showed that the native iron core ferritin is intact and that no degradation occurs during chemical functionalization of the protein shell. The NBD-labeled ferritin particles are water soluble, which allowed their controlled deposition by the Langmuir–Blodgett (LB) technique. Superparamagnetic and fluorescent properties of the particles are preserved within the LB film.     

Synthesis and characterization of folic acid-chitosan nanoparticles loaded with thymoquinone to target ovarian cancer cells

The aim of the present research was to formulate and characterize radioiodinated folic acid-chitosan conjugated thymoquinone nanoparticles (FATQCSNPs) and to increase targeting ability on ovarian cancer cell. The dose of drug-loading into the FATQCSNPs and the amount of folic acid on the FATQCSNPs surface were determined as a 20.0?±?1% and 46.0?±?0.5%, respectively. Cell viabilities (%) determined on SKOV-3 and Caco-2 cells for 48 h. TQ, TQCS and FATQCS were very cytotoxic with lower IC₅₀ values on both cell lines. At specific-activity-dependent incorporation study, the incorporation efficiencies of ¹³¹I-FATQCSNPs was higher than that of ¹³¹I-TQ on SKOV3 cell lines.

     

A coordination cage hosting ultrafine and highly catalytically active gold nanoparticles

Ultrafine metal nanoparticles (MNPs) with size <2 nm are of great interest due to their superior catalytic capabilities. Herein, we report the size-controlled synthesis of gold nanoparticles (Au NPs) by using a thiacalixarene-based coordination cage CIAC-108 as a confined host or stabilizer. The Au NPs encapsulated within the cavity of CIAC-108 (Au@CIAC-108) show smaller size (∼1.3 nm) than the ones (∼4.7 nm) anchored on the surface of CIAC-108 (Au/CIAC-108). The cage-embedded Au NPs can be used as a homogeneous catalyst in a mixture of methanol and dichloromethane while as a heterogeneous catalyst in methanol. The homogeneous catalyst Au@CIAC-108-homo exhibits significantly enhanced catalytic activities toward nitroarene reduction and organic dye decomposition, as compared with its larger counterpart Au/CIAC-108-homo and its heterogeneous counterpart Au@CIAC-108-hetero. More importantly, the as-prepared Au@CIAC-108-homo possesses remarkable stability and durability.

The size-controlled synthesis of Au NPs was achieved by using a coordination cage CIAC-108 as a support. The Au NPs encapsulated within the cavity of CIAC-108 show smaller size (∼1.3 nm) than the ones (∼4.7 nm) anchored on the surface of CIAC-108.     

Anticancer drug-loaded gliadin nanoparticles induce apoptosis in breast cancer cells

Nanoscale drug carriers play an important role in regulating the delivery, permeability, and retention of the drugs. Although various carriers have been used to encapsulate anticancer drugs, natural biomaterials are of great benefit for delivery and controlled release of drugs. We used the electrospray deposition system to synthesize gliadin and gliadin-gelatin composite nanoparticles for delivery and controlled release of an anticancer drug (e.g., cyclophosphamide). The size profile and synthesis of nanoparticles was characterized by dynamic light scattering and X-ray diffractometry. Cyclophosphamide was gradually released from the gliadin nanoparticles for 48 h. In contrast, the gliadin-gelatin composite nanoparticles released cyclophosphamide in a rapid manner. Furthermore, we demonstrated that breast cancer cells cultured with cyclophosphamide-loaded 7% gliadin nanoparticles for 24 h became apoptotic, confirmed by Western blotting analysis. Therefore, the gliadin-based nanoparticle could be a powerful tool for delivery and controlled release of anticancer drugs.     

Transformable peptide nanoparticles inhibit the migration of N-cadherin overexpressed cancer cells

About 90% cancer-related mortality results from the cancer metastasis, which generally undergoes after epithelial-mesenchymal transition (EMT) process. N-Cadherin, overexpressed on cancer cell surface during EMT, can enhance the migration of cancer cells. Herein, we design and synthesize a transformable peptide BP-KLVFF-SWTLYTPSGQSK (BFS) that can block N-cadherin for inhibiting cancer migration and metastasis. The peptide BFS consists of three modules including (1) the hydrophobic bis-pyrene (BP) unit for forming and locating nanoparticles, (2) the KLVFF peptide sequence for forming and stabilizing fibrous structures and (3) the targeting peptide sequence SWTLYTPSGQSK that can specifically bind to N-cadherin. The peptide BFS can form nanoparticles in PBS, which can transform to nanofibers when targeting and binding to N-cadherin. The nanofibers inhibit the migration of N-cadherin overexpressed MDA-MB-436 cancer cells. The peptide BFS shows 83.6% inhibiting rate in cells wound healing assay. In addition, the inhibition rate is 67.9% when the BFS applied in transwell migration assay. These results indicate that the BFS has excellent ability to inhibit migration of cancer cells. This self-assembly strategy could be potentially utilized to regulate the key protein during EMT for inhibiting the tumor metastasis.