Ahmad Amirshaghaghi

A pH‐Responsive Drug‐Delivery Platform Based on Glycol Chitosan–Coated Liposomes

Currently, a substantial amount of effort is focused on developing actively targeted, receptor-specific nanoparticles for the delivery of anticancer drugs and diagnostic imaging contrast agents.[1–7] Receptor-targeted nanoparticles hold much promise and are often shown to provide nanoparticle delivery beyond that seen with the enhanced permeability and retention (EPR) effect alone. However, these nanoparticles still face considerable challenges as a result of the significant heterogeneity in receptor expression, not only between patients and tumor types, but also within individual tumors.[8] In many cases, the overexpressed receptor may also be present on normal tissues leading to detrimental off-target effects. Perhaps even more troubling is that several recent studies have shown that cancer stem cells may not even possess any known up-regulated receptor.[9] Therefore, targeting strategies that are more generalizable across a broad range of tumors than receptor-specific targeting are highly desirable.

Chemo-photothermal therapy of cancer cells using gold nanorod-cored stimuli-responsive triblock copolymer

Light-based therapies including photothermal therapy have been validated clinically for curative and palliative treatment of solid tumors. However, these monotherapies can suffer from incomplete tumor killing and have not displaced existing ablative modalities. The combination of photothermal therapy and chemotherapy, when carefully planned, has been shown to be an effective cancer treatment option clinically and preclinically. According to these facts, gold nanorod-cored biodegradable micelles were prepared by coating gold nanorods (GNRs) with a synthesized stimuli-responsive thiol-end capped ABC triblock copolymer [poly(acrylic acid)-b-poly(N-isopropylacrylamide)-b-poly(e-caprolactone)-SH; PAA-b-PNIPAAm-b-PCL-SH]. Furthermore, the anti-cancer drug doxorubicin (DOX) was conjugated onto the gold nanorod-cored micelles (GNR@polymer) by electrostatic force and the nanocomposites formed were named GNR@polymer–DOX. The success of the coating was investigated by means of thermogravimetric analysis (TGA), Fourier transform infrared (FTIR) spectroscopy, atomic force microscopy (AFM), X-ray powder diffraction (XRD), transmission electron microscopy (TEM), ultraviolet-visible (UV-vis) spectroscopy, as well as dynamic light scattering (DLS), and zeta potential (ξ) measurements. DOX-loading capacity and stimuli-responsive drug release ability of the synthesized nanocomposites were also investigated. The in vitro therapy effect was comprehensively evaluated among free DOX, GNR@polymer, and GNR@polymer–DOX, with or without NIR light irradiation (1064 nm, 137 mJ per pulse, 3 min) to improve the curative effect of GNR@polymer–DOX led by the combination of chemotherapy and photothermal therapy.

Preparation and evaluation of a layered double hydroxide film on a nanoporous anodic aluminum oxide/aluminum wire as a highly thermal-resistant solid-phase microextraction fiber

A hierarchical ZnAl layered double hydroxide (ZnAl-LDH) framework has been fabricated via the in situ crystallization technique on a nonporous anodic aluminum oxide/aluminum wire (AAO/Al) as both the substrate and the aluminum source. The prepared wire with a high surface area and a uniform and compact structure was used as a solid phase microextraction (SPME) fiber for separation and determination of phenolic compounds from aqueous solutions in combination with gas chromatography–mass spectrometry (GC–MS). The fabricated LDH/AAO/AL wire displays flowerlike LDH microspheres composed of numerous LDH nanoplatelets, which was confirmed by the SEM image. The novel SPME fiber was evaluated for the extraction of some phenolic compounds (PCs) from water and wastewater sample solutions in combination with gas chromatography–mass spectrometry. A one at-a-time optimization strategy was applied for optimizing the important extraction parameters such as extraction temperature, extraction time, stirring rate, pH, ionic strength and desorption time and temperature. Under optimum conditions, the repeatability for one fiber (n = 3), expressed as relative standard deviation (R.S.D.%), was between 4.3% and 9.7% for the test compounds. The detection limits for the studied compounds were between 4 and 9 pg mL−1. The developed method offers the advantage of being simple to use, with lower cost of equipment, shorter analysis time, thermal stability of the fiber and high relative recovery in comparison to conventional methods of analysis.

Protoporphyrin IX (PpIX)‐Coated Superparamagnetic Iron Oxide Nanoparticle (SPION) Nanoclusters for Magnetic Resonance Imaging and Photodynamic Therapy

The ability to produce nanotherapeutics at large-scale with high drug loading efficiency, high drug loading capacity, high stability, and high potency is critical for clinical translation. However, many nanoparticle-based therapeutics under investigation suffer from complicated synthesis, poor reproducibility, low stability, and high cost. In this work, a simple method for preparing multifunctional nanoparticles is utilized that act as both a contrast agent for magnetic resonance imaging and a photosensitizer for photodynamic therapy for the treatment of cancer. In particular, the photosensitizer protoporphyrin IX (PpIX) is used to solubilize small nanoclusters of superparamagnetic iron oxide nanoparticles (SPIONs) without the use of any additional carrier materials. These nanoclusters are characterized with a high PpIX loading efficiency; a high loading capacity, stable behavior; high potency; and a synthetic approach that is amenable to large-scale production. In vivo studies of photodynamic therapy (PDT) efficacy show that the PpIX-coated SPION nanoclusters lead to a significant reduction in the growth rate of tumors in a syngeneic murine tumor model compared to both free PpIX and PpIX-loaded poly(ethylene glycol)-polycaprolactone micelles, even when injected at 1/8th the dose. These results suggest that the nanoclusters developed in this work can be a promising nanotherapeutic for clinical translation.

Photoacoustic-Guided Surgery with Indocyanine Green-Coated Superparamagnetic Iron Oxide Nanoparticle Clusters

A common cause of local tumor recurrence in brain tumor surgery results from incomplete surgical resection. Adjunctive technologies meant to facilitate gross total resection have had limited efficacy to date. Contrast agents used to delineate tumors preoperatively cannot be easily or accurately used in the real-time operative setting. Although multimodal imaging contrast agents are developed to help the surgeon discern tumor from normal tissue in the operating room, these contrast agents are not readily translatable. This study has developed a novel contrast agent comprised solely of two Food and Drug Administration approved components, indocyanine green (ICG) and superparamagnetic iron oxide (SPIO) nanoparticles-with no additional amphiphiles or carrier materials, to enable preoperative detection by magnetic resonance (MR) imaging and intraoperative photoacoustic (PA) imaging. The encapsulation efficiency of both ICG and SPIO within the formulated clusters is ≈100%, and the total ICG payload is 20-30% of the total weight (ICG + SPIO). The ICG-SPIO clusters are stable in physiologic conditions; can be taken up within tumors by enhanced permeability and retention; and are detectable by MR. In a preclinical surgical resection model in mice, following injection of ICG-SPIO clusters, animals undergoing PA-guided surgery demonstrate increased progression-free survival compared to animals undergoing microscopic surgery.

Wulff in a cage gold nanoparticles as contrast agents for computed tomography and photoacoustic imaging

Nanostructures have potential for use in biomedical applications such as sensing, imaging, therapeutics, and drug delivery. Among nanomaterials, gold nanostructures are of considerable interest for biomedical research, owing to their bio-inertness, controllable surface chemistry, X-ray opacity, and optical properties. Gold nanocages are particularly attractive for imaging and therapeutic applications, because they strongly absorb light in the near infra-red region which has high light transmission in tissue. However, the X-ray attenuation of nanocages is relatively low due to their hollow structure. In this study, for the first time, we sought to combine the attractive optical properties of nanoshells with the high payloads of solid nanoparticles and investigated their biomedical applications. Here, we report the engineering of Wulff in a cage nanoparticles via converting gold Wulff-shaped seeds into gold-silver core-shell structures and then performing a galvanic replacement reaction. The structure of these nanoparticles was determined using transition electron microscopy. This morphological transformation of gold nanoparticles shaped as truncated octahedrons into a complex Wulff in a cage nanoparticles during the reaction resulted in extensive changes in their optical properties that made these unique structures a potential contrast agent for photoacoustic imaging. We found that the Wulff in a cage nanoparticles had no adverse effects on the viabilities of J774A.1, Renca, and HepG2 cells at any of the concentrations tested. In vitro and in vivo experiments showed robust signals in both photoacoustic imaging and computed tomography. To the best of our knowledge, this is the first report of Wulff in a cage nanoparticles serving as a platform for multiple imaging modalities. This unique multifunctional nanostructure, which integrates the competencies of both core and shell structures, allows their use as contrast agents for photoacoustic imaging, computed tomography and as a potential agent for photothermal therapy.

Site-Specific Labeling of Cyanine and Porphyrin Dye-Stabilized Nanoemulsions with Affibodies for Cellular Targeting

Recently, it has been shown that amphiphilic dyes such as Indocyanine Green (ICG) and Protoporphyrin IX (PpIX) can solubilize hydrophobic colloids and/or drugs by driving the formation of stable nanoemulsions. These nanoemulsions are unique in that they can be composed entirely of functional and clinically used materials; however, they lack bio-orthogonal chemical handles for the facile attachment of targeting ligands. The ability to target nanoparticles is desirable because it can lead to improved specificity and reduced side effects. Here, we describe variants of ICG and PpIX with azide handles that can be readily incorporated into dye-stabilized nanoemulsions and facilitate the attachment of targeting ligands via click-chemistry in a simple, scalable, and reproducible reaction. As a model system, an anti-Her2 affibody was site-specifically attached to both ICG and PpIX-stabilized nanoemulsions with encapsulated superparamagnetic iron oxide nanoparticles.