Dual-Function Nanoscale Coordination Polymer Nanoparticles for Targeted Diagnosis and Therapeutic Delivery in Atherosclerosis.

Atherosclerosis is the primary cause of cardiovascular events such as heart attacks and strokes. However, current medical practice lacks non-invasive, reliable approaches for both imaging atherosclerotic plaques and delivering therapeutic agents directly therein. Here, a biocompatible and biodegradable pH-responsive nanoscale coordination polymers (NCPs) based theranostic system is reported for managing atherosclerosis. NCPs are synthesized with a pH-responsive benzoic-imine (BI) linker and Gd3+. Simvastatin (ST), a statin not used for lowering blood cholesterol but known for its anti-inflammatory and antioxidant effects in mice, is chosen as the model drug. By incorporating ST into the hydrophobic domain of a lipid bilayer shell on NCPs surfaces, ST/NCP-PEG nanoparticles are created that are designed for dual purposes: they diagnose and treat atherosclerosis. When administered intravenously, they target atherosclerotic plaques, breaking down in the mild acidic microenvironment of the plaque to release ST, which reduces inflammation and oxidative stress, and Gd-complexes for MR imaging of the plaques. ST/NCP-PEG nanoparticles show efficacy in slowing the progression of atherosclerosis in live models and allow for simultaneous in vivo monitoring without observed toxicity in major organs. This positions ST/NCP-PEG nanoparticles as a promising strategy for the spontaneous diagnosis and treatment of atherosclerosis.

Injectable liposomal docosahexaenoic acid alleviates atherosclerosis progression and enhances plaque stability.

Atherosclerosis is a chronic inflammatory vascular disease that is characterized by the accumulation of lipids and immune cells in plaques built up inside artery walls. Docosahexaenoic acid (DHA, 22:6n-3), an omega-3 polyunsaturated fatty acid (PUFA), which exerts anti-inflammatory and antioxidant properties, has long been purported to be of therapeutic benefit to atherosclerosis patients. However, large clinical trials have yielded inconsistent data, likely due to variations in the formulation, dosage, and bioavailability of DHA following oral intake. To fully exploit its potential therapeutic effects, we have developed an injectable liposomal DHA formulation intended for intravenous administration as a plaque-targeted nanomedicine. The liposomal formulation protects DHA against chemical degradation and increases its local concentration within atherosclerotic lesions. Mechanistically, DHA liposomes are readily phagocytosed by activated macrophages, exert potent anti-inflammatory and antioxidant effects, and inhibit foam cell formation. Upon intravenous administration, DHA liposomes accumulate preferentially in atherosclerotic lesional macrophages and promote polarization of macrophages towards an anti-inflammatory M2 phenotype, resulting in attenuation of atherosclerosis progression in both ApoE-/- and Ldlr-/- experimental models. Plaque composition analysis demonstrates that liposomal DHA inhibits macrophage infiltration, reduces lipid deposition, and increases collagen content, thus improving the stability of atherosclerotic plaques against rupture. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) further reveals that DHA liposomes can partly restore the complex lipid profile of the plaques to that of early-stage plaques. In conclusion, DHA liposomes offer a promising approach for applying DHA to stabilize atherosclerotic plaques and attenuate atherosclerosis progression, thereby preventing atherosclerosis-related cardiovascular events.

Gold nanoparticle-gated mesoporous silica as redox-triggered drug delivery for chemo-photothermal synergistic therapy.

In this paper, a redox-triggered drug delivery system of DOX/MSN-Au was prepared for chemo-photothermal synergistic therapy. The ultra-small gold nanoparticles (NPs) were appended to the openings of mesoporous silica nanoparticles (MSN) by Au-S bonds as the gatekeepers. Meanwhile, the gold NPs could be heated to high temperature by the near infrared (NIR) light irradiation, which is conducive to photothermal therapy. X-ray photoelectron spectroscopy (XPS) and Fourier Transform Infrared Spectrometer (FT-IR) spectra confirmed the formation of MSN-SH and MSN-Au. An in vitro NIR-induced photothermal study indicated that MSN-Au possessed concentration-dependent and power-dependent photothermal conversion capacity. Doxorubicin (DOX) was selected as the model drug loaded in the MSN. In vitro drug release showed that DOX released faster in the presence of glutathione (GSH) or NIR laser irradiation than without GSH or NIR irradiation, which suggested that the system had potentials for redox-responsive and NIR-triggered drug release. Confocal Laser Scanning Microscope (CLSM) was performed to evaluate the cellular uptake performance of DOX/MSN-Au. The cytotoxicity assay indicated that DOX/MSN-Au had a synergistic therapeutic effect by the combination of chemotherapy and photothermal therapy. This work suggested that MSN-Au could be explored as a redox-triggered drug delivery system for the chemo-photothermal synergistic therapy.

Fluorescent carbon dot gated hollow mesoporous carbon for chemo-photothermal synergistic therapy.

An efficient and intelligent nano-carrier that combines cell imaging with near infrared (NIR) light and redox dual-responsive drug delivery was successfully prepared. The hollow mesoporous carbon (HMC) nanoparticles with high photothermal conversion ability were developed to increase the drug loading efficiency and realize chemotherapy and photothermal synergetic therapy. The photo-stable and luminescent carbon dots (CDs) were prepared from branched polyethyleneimine (PEI) by hydrothermal reaction. The PEI CDs (CDPEI) were grafted on the openings of HMC as the "gatekeepers" via disulfide units (HMC-SS-CDPEI) to prevent the premature release of doxorubicin (DOX). In the presence of GSH, the CDPEI separated from HMC due to the breakage of disulfide bonds, thus triggering the rapid release of the encapsulated drug. In addition, the release rate of DOX could be further accelerated by NIR light irradiation due to the increased temperature which would decrease the interaction between HMC and DOX. The fluorescence of the CDPEI is quenched when being attached to the HMC, while it is recovered when the CDPEI breaking away from HMC. Hence, the fluorescent CDPEI not only act as a gatekeeper to control drug release but also play a vital role in monitoring the process of the drug delivery. The developed HMC-SS-CDPEI showed dual-responsive drug release property and could be used as visible nano-platforms for chemo-photothermal synergistic therapy.

Mesoporous carbon nanomaterials in drug delivery and biomedical application.

Recent development of nano-technology provides highly efficient and versatile treatment methods to achieve better therapeutic efficacy and lower side effects of malignant cancer. The exploration of drug delivery systems (DDSs) based on nano-material shows great promise in translating nano-technology to clinical use to benefit patients. As an emerging inorganic nanomaterial, mesoporous carbon nanomaterials (MCNs) possess both the mesoporous structure and the carbonaceous composition, endowing them with superior nature compared with mesoporous silica nanomaterials and other carbon-based materials, such as carbon nanotube, graphene and fullerene. In this review, we highlighted the cutting-edge progress of carbon nanomaterials as drug delivery systems (DDSs), including immediate/sustained drug delivery systems and controlled/targeted drug delivery systems. In addition, several representative biomedical applications of mesoporous carbon such as (1) photo-chemo synergistic therapy; (2) delivery of therapeutic biomolecule and (3) in vivo bioimaging are discussed and integrated. Finally, potential challenges and outlook for future development of mesoporous carbon in biomedical fields have been discussed in detail.

Hollow mesoporous carbon as a near-infrared absorbing carrier compared with mesoporous carbon nanoparticles for chemo-photothermal therapy.

In this study, hollow mesoporous carbon nanoparticles (HMCN) and mesoporous carbon nanoparticles (MCN) were used as near-infrared region (NIR) nanomaterials and drug nanocarriers were prepared using different methods. A comparison between HMCN and MCN was performed with regard to the NIR-induced photothermal effect and drug loading efficiency. The results of NIR-induced photothermal effect test demonstrated that HMCN-COOH had a better photothermal conversion efficacy than MCN-COOH. Given the prominent photothermal effect of HMCN-COOH in vitro, the chemotherapeutic drug DOX was chosen as a model drug to further evaluate the drug loading efficiencies and NIR-triggered drug release behaviors of the nanocarriers. The drug loading efficiency of DOX/HMCN-COOH was found to be up to 76.9%, which was higher than that of DOX/MCN-COOH. In addition, the use of an 808nm NIR laser markedly increased the release of DOX from both carbon carriers in pH 5.0 PBS and pH 7.4 PBS. Cellular photothermal tests involving A549 cells demonstrated that HMCN-COOH had a much higher photothermal efficacy than MCN-COOH. Cell viability experiments and flow cytometry were performed to evaluate the therapeutic effect of DOX/HMCN-COOH and the results obtained demonstrated that DOX/HMCN-COOH had a synergistic therapeutic effect in cancer treatment involving a combination of chemotherapy and photothermal therapy.