Understanding Nanoparticle Toxicity to Direct a Safe-by-Design Approach in Cancer Nanomedicine

Nanomedicine is a rapidly growing field that uses nanomaterials for the diagnosis, treatment and prevention of various diseases, including cancer. Various biocompatible nanoplatforms with diversified capabilities for tumor targeting, imaging, and therapy have materialized to yield individualized therapy. However, due to their unique properties brought about by their small size, safety concerns have emerged as their physicochemical properties can lead to altered pharmacokinetics, with the potential to cross biological barriers. In addition, the intrinsic toxicity of some of the inorganic materials (i.e., heavy metals) and their ability to accumulate and persist in the human body has been a challenge to their translation. Successful clinical translation of these nanoparticles is heavily dependent on their stability, circulation time, access and bioavailability to disease sites, and their safety profile. This review covers preclinical and clinical inorganic-nanoparticle based nanomaterial utilized for cancer imaging and therapeutics. A special emphasis is put on the rational design to develop non-toxic/safe inorganic nanoparticle constructs to increase their viability as translatable nanomedicine for cancer therapies

Integration of Electrospun Scaffolds and Biological Polymers for Enhancing the Delivery and Efficacy of Mesenchymal Stem/Stromal Cell Therapies

Mesenchymal stem/stromal cells (MSCs) have emerged as a promising therapeutic approach for a variety of diseases due to their immunomodulatory and tissue regeneration capabilities. Despite their potential, the clinical application of MSC therapies is hindered by limited cell retention and engraftment at the target sites. Electrospun scaffolds, with their high surface area-to-volume ratio and tunable physicochemical properties, can be used as platforms for MSC delivery. However, synthetic polymers often lack the bioactive cues necessary for optimal cell-scaffold interactions. Integrating electrospun scaffolds and biological polymers, such as polysaccharides, proteins, and composites, combines the mechanical integrity of synthetic materials with the bioactivity of natural polymers and represents a strategic approach to enhance cell-scaffold interactions. The molecular interactions between MSCs and blended or functionalized scaffolds have been examined in recent studies, and it has been shown that integration can enhance MSC adhesion, proliferation, and paracrine secretion through the activation of multiple signaling pathways, such as FAK/Src, MAPK, PI3K/Akt, Wnt/β-catenin, and YAP/TAZ. Preclinical studies on small animals also reveal that the integration of electrospun scaffolds and natural polymers represents a promising approach to enhancing the delivery and efficacy of MSCs in the context of regenerating bone, cartilage, muscle, cardiac, vascular, and nervous tissues. Future research should concentrate on identifying the distinct characteristics of the MSC niche, investigating the processes involved in MSC-scaffold interactions, and applying new technologies in stem cell treatment and biofabrication to enhance scaffold design. Research on large animal models and collaboration among materials scientists, engineers, and physicians are crucial to translating these advancements into clinical use

The Synthesis and Characterization of Gadolinium Alginate Spheres and Potential Uses as a Contrast-Enhancing Anti-Cancer Material

https://openworks.mdanderson.org/sumexp23/1032/thumbnail.jp

Radiopaque Nanoparticle and Dipyridamole-loaded Electrospun Polymeric Scaffold as Bioresorbable Drug-Eluting Vascular Graft

https://openworks.mdanderson.org/sumexp22/1080/thumbnail.jp

Electrospun Bioresorbable Polymer Blends as Vascular Grafts

https://openworks.mdanderson.org/sumexp23/1089/thumbnail.jp

Alendronate Conjugate for Targeted Delivery to Bone-Forming Prostate Cancer

Bone is the primary metastasis site for lethal prostate cancer, often resulting in poor prognosis, crippling pain, and diminished functioning that drastically reduce both quality of life and survivability Uniquely, prostate cancer bone metastasis induces aberrant bone overgrowth, due to an increase of osteoblasts induced by tumor-secreted bone morphogenetic protein 4 (BMP4). Conjugating drugs to substances that target the tumor-induced bone area within the metastatic tumor foci would be a promising strategy for drug delivery. To develop such a strategy, we conjugated a near infrared (NIR) fluorescent probe, the dye Cy5.5, to serve as a surrogate for drugs, with alendronate, which targets bone. Characterization, such as infrared spectroscopy, confirmed the synthesis of the Cy5.5-ALN conjugate. The maximum absorbance of free Cy5.5, which was at 675 nm, did not change upon conjugation. Alendronate targeted the bone component hydroxyapatite in a dose-dependent manner up to 2.5 μM, with a maximum of 85% of Cy5.5-ALN bound to hydroxyapatite, while free Cy5.5 alone had 6% binding. In in vitro cell binding studies, Cy5.5-ALN bound specifically with mineralized bone matrix of differentiated MC3T3-E1 cells or 2H11 endothelial cells that were induced to become osteoblasts through endothelial-to-osteoblast transition, the underlying mechanism of prostate-cancer-induced bone formation. Neither Cy5.5-ALN nor free Cy5.5 bound to undifferentiated MC3T3-E1 or 2H11 cells. Bone-targeting efficiency studies in non-tumor-bearing mice revealed accumulation over time in the spine, jaw, knees, and paws injected with Cy5.5-ALN, and quantification showed higher accumulation in femurs than in muscle at up to 28 days, while the free Cy5.5 dye was observed circulating without preferential accumulation and decreased over time. There was a linear relationship with fluorescence when the injected concentration of Cy5.5-ALN was between 0.313 and 1.25 nmol/27 g of mouse, as quantified in mouse femurs both in vivo and ex vivo. Ex vivo evaluation of bone-targeting efficiency in nude mice was 3 times higher for bone-forming C4-2b-BMP4 tumors compared to non-bone-forming C4-2b tumors (p-value \u3c0.001). Fluorescence microscopy imaging of the tumors showed that Cy5.5-ALN co-localized with the bone matrix surrounding tumor-induced bone, but not with the viable tumor cells. Together, these results suggest that a drug-ALN conjugate is a promising approach for targeted delivery of drug to the tumor-induced bone area in the metastatic foci of prostate cancer

Pre-operative portal vein ligation and MSC injection in a rat model

https://openworks.mdanderson.org/sumexp23/1047/thumbnail.jp

On the inheritance of crystallographic texture during the nickel silicide solid-phase reaction

Irreversible electroporation (IRE) is an emerging minimally invasive tumor ablation technique that delivers short pulses of strong electric fields and kills cancer cells by disrupting their cell membranes with the electric pulses. However, clinical studies report that more than 10% of local tumor recurrences occur at the original ablated site. NVP BEZ-235 (BEZ) is a dual PI3K/mTOR inhibitor that has substantial anticancer effects. However, the clinical trials of BEZ was not satisfactory because of its low bioavailability and high toxicity, which stemmed from the use of oral administration of high doses over a long period of time. In this research, we prepared a liposomal formulation of BEZ (L-BEZ) for intratumoral injection and studied its antitumor efficacy alone and in combination with IRE. We hypothesized that IRE could release BEZ from the liposomes and that the combination could decrease tumor viability. Our results show that IRE released BEZ from its liposomal encapsulation. The combination of L-BEZ and IRE killed more Hep3B tumor cells in vitro than did L-BEZ or IRE alone and also inhibited cancer cell proliferation in nude mice bearing Hep3B xenografts. Combination of chemotherapeutic agent loaded nanoparticles could enhance the antitumor efficacy of IRE

Tungsten nanoparticle and polymer blends as novel coating for radiopaque resorbable inferior vena cava filter

https://openworks.mdanderson.org/sumexp22/1148/thumbnail.jp

Image-Guided Deployment and Monitoring of a Novel Tungsten Nanoparticle-Infused Radiopaque Absorbable Inferior Vena Cava Filter in a Swine Model

PURPOSE: To improve radiopacity of radiolucent absorbable poly-p-dioxanone (PPDO) inferior vena cava filters (IVCFs) and demostrate their effectiveness in clot-trapping ability. MATERIALS AND METHODS: Tungsten nanoparticles (WNPs) were incorporated along with polyhydroxybutyrate (PHB), polycaprolactone (PCL), and polyvinylpyrrolidone (PVP) polymers to increase the surface adsorption of WNPs. The physicochemical and in vitro and in vivo imaging properties of PPDO IVCFs with WNPs with single-polymer PHB (W-P) were compared with those of WNPs with polymer blends consisting of PHB, PCL, and PVP (W-PB). RESULTS: In vitro analyses using PPDO sutures showed enhanced radiopacity with either W-P or W-PB coating, without compromising the inherent physicomechanical properties of the PPDO sutures. W-P- and W-PB-coated IVCFs were deployed successfully into the inferior vena cava of pig models with monitoring by fluoroscopy. At the time of deployment, W-PB-coated IVCFs showed a 2-fold increase in radiopacity compared to W-P-coated IVCFs. Longitudinal monitoring of in vivo IVCFs over a 12-week period showed a drastic decrease in radiopacity at Week 3 for both filters. CONCLUSIONS: The results highlight the utility of nanoparticles (NPs) and polymers for enhancing radiopacity of medical devices. Different methods of incorporating NPs and polymers can still be explored to improve the effectiveness, safety, and quality of absorbable IVCFs