Tumour microenvironment hinders nanoparticle transport deep into the tissue precluding thorough treatment of solid tumours and metastatic nodes. We introduce an anticancer drug delivery concept ...termed FlaRE (Flash Release in Endothelium), which represents alternative to the existing approaches based on enhanced permeability and retention effect. This approach relies on enhanced drug-loaded nanocarrier accumulation in vessels of the target tumour or metastasised organ, followed by a rapid release of encapsulated drug within tens of minutes. It leads to a gradient-driven permeation of the drug to the target tissue. This pharmaceutical delivery approach is predicted by theoretical modelling and validated experimentally using rationally designed MIL-101(Fe) metal-organic frameworks. Doxorubicin-loaded MIL-101 nanoparticles get swiftly trapped in the vasculature of the metastasised lungs, disassemble in the blood vessels within 15 minutes and release drug, which rapidly impregnates the organ. A significant improvement of the therapeutic outcome is demonstrated in animal models of early and late-stage B16-F1 melanoma metastases with 11-fold and 4.3-fold decrease of pulmonary melanoma nodes, respectively.
Hybrid multimodal nanoparticles, applicable simultaneously to the noninvasive imaging and therapeutic treatment, are highly demanded for clinical use. Here, Fe-Au core-satellite nanoparticles ...prepared by the method of pulsed laser ablation in liquids were evaluated as dual magnetic resonance imaging (MRI) and computed tomography (CT) contrast agents and as sensitizers for laser-induced hyperthermia of cancer cells. The biocompatibility of Fe-Au nanoparticles was improved by coating with polyacrylic acid, which provided excellent colloidal stability of nanoparticles with highly negative ζ-potential in water (-38 ± 7 mV) and retained hydrodynamic size (88 ± 20 nm) in a physiological environment. The ferromagnetic iron cores offered great contrast in MRI images with r
= 11.8 ± 0.8 mM
s
(at 1 T), while Au satellites showed X-ray attenuation in CT. The intravenous injection of nanoparticles enabled clear tumor border visualization in mice. Plasmonic peak in the Fe-Au hybrids had a tail in the near-infrared region (NIR), allowing them to cause hyperthermia under 808 nm laser exposure. Under NIR irradiation Fe-Au particles provided 24.1 °C/W heating and an IC
value below 32 µg/mL for three different cancer cell lines. Taken together, these results show that laser synthesized Fe-Au core-satellite nanoparticles are excellent theranostic agents with multimodal imaging and photothermal capabilities.
•Photoacoustic method for measurement of nanoparticle degradation was introduced.•Photoacoustic showed polyallylamine coat promoted silicon nanoparticle dissolution.•Polyallylamine-coated silicon ...particles blocked macrophages in vitro and in vivo.•Blockade by silicon particles enhanced tumour uptake of magnetic particles 13-fold.
Nanomaterials with controllable biodegradation properties respond to the main challenge of cancer nanomedicine to minimise side effects and maximise the delivery efficacy to tumours. These biodegradation properties vary from clear aqueous solutions to protein-abundant biological fluids. A photoacoustic method suitable for in vitro quantification of highly scattering colloids with optical absorption properties is introduced and demonstrated by determination of the degradation rate of laser-synthesized silicon nanoparticles (Si NPs) in turbid serum solutions. In vitro screening of a variety of polymer surface-coatings of Si NPs revealed a stand-alone property of polyallylamine (PAA) to accelerate the Si NP dissolution. PAA-coated Si NP half-life was measured ∼ 100-min in aqueous solutions and slowed down to ∼ 24 h in serum. As-produced PAA-coated Si NPs appeared suitable for blockade of the mononuclear phagocyte system. Pre-treatment with PAA-Si NPs caused 1.4-times reduced uptake of magnetic particles by human THP-1 cells in vitro and a 13-fold increase of the magnetic particle delivery to the B16-F1 xenograft tumours in vivo. The demonstrated photoacoustic method is believed to facilitate design and screening of biodegradable materials suitable for in vivo applications such as controlled drug release.
The development of nanozymes, artificial enzymes made from inorganic nanoparticles, is widely studied due to their affordability, durability, and strength. Gold nanoparticles (AuNPs) are employed to ...imitate peroxidase, glucose oxidase, lactate oxidase, superoxide dismutase, and catalase. The last one transforms intracellular hydrogen peroxide into molecular oxygen, whose deficiency is characteristic of the hypoxic tumor microenvironment. Thus, gold nanoparticles are thought to enhance the overall effectiveness of photodynamic therapy. However, the enzyme‐like activity of nanoparticles rapidly decreases in biological media, due to the aggregation and formation of the so‐called “protein corona”. In this study, polymeric submicrocapsules loaded with AuNPs and a photodynamic dye are fabricated via Layer‐by‐Layer (LbL) assembly. The enhancement of photodynamic treatment efficacy by in situ production of oxygen by the catalase‐like effect of AuNPs is investigated. Polymeric capsules are thoroughly characterized in terms of physicochemical and catalytic properties, and as a proof of concept, their therapeutic potential is evaluated in vitro. Furthermore, encapsulated AuNPs shows significantly lower aggregation both upon storage and during the reaction course. The results shows that the polymer capsules, containing AuNPs and photodynamic dye, show significantly higher light‐induced cytotoxicity in comparison to the individual photodynamic dye, suggesting a synergistic effect between the formation of molecular oxygen by catalase‐like gold nanozymes and photodynamic action.
Polymeric submicrocapsules loaded with gold nanoparticles (AuNPs) and a photodynamic dye (PS) are fabricated via layer‐by‐layer (LbL) assembly. Encapsulated AuNPs shows lower aggregation upon storage and during the reaction course. The results show that polymer capsules, containing AuNPs and PS, show significantly higher light‐induced cytotoxicity compared to individual PS, suggesting a synergistic effect between AuNPs and PS.
