Efficient Nanoplatform Research Articles

Glutathione and pH-responsive chitosan-based nanogel as an efficient nanoplatform for controlled delivery of doxorubicin

Incomplete delivery of drugs to the cancerous tissue and the drug resistance mechanisms limit the medical applications of anticancer drugs. Colloidal systems offers many advantages owing to the non-invasive way of drug administration as well as centralized delivery of anti-cancer drugs to tumor tissue. Nanogels (Ngs) as a part of these colloidal systems have a good perspective for their ability to incorporate and encapsulate low-molecular-mass drugs, bio-macromolecules, and proteins. Therefore, we developed pH and redox-responsive Ngs to provide a hopeful prospect for targeted delivery of anti-cancer drugs in cancer cells. For this purpose, chitosan (CS) was first modified with a chain transfer agent (CTA) and then, the polymerization of 2-Hydroxyethyl methacrylate (HEMA) monomer occurred to create (CTS-g-PHEMA). Hydroxyl groups of HEMA reacted with maleic anhydride molecules to prepare CTS-g-PHEMA-maleic acid (MAc). Finally, the double bonds of MAc were used for the grafting of N, N′ bis(acryloyl) cystamine (BAC) as a crosslinker agent to prepare redox-sensitive Ngs. The biocompatibility, chemical structures, DOX loading capacity, content of the drug released and in-vitro cytotoxicity effects were also studied. As a result, it is expected that Ngs can be applied as a potential nanomedicine carrier for the treatment of cancer.

P1216Evaluation of alphavbeta3 integrin-targeted positron emission tomography and photoacoustic tracer for imaging of carotid plaque in apoE–/– mice

Abstract Background Cardiovascular disease is the leading cause of death in the world. The majority of cardiovascular events result from the rupture of vulnerable atherosclerotic plaques, which are characterized by high and active macrophage content. The integrin αVβ3 is expressed by activated macrophages and endothelial cells in atherosclerotic lesions and thus is a marker of high-risk plaques. Therefore, 89Zr-RGD-melanin nanoparticle (MNP) positron emission tomography (PET)/photoacoustic imaging (PAI) imaging of αVβ3 expression in plaques might provide a novel noninvasive biomarker of plaque vulnerability. Purpose In this study, the intrinsic photoacoustic signals and the native strong chelating properties with metal ions of MNP, positron-emitting metal ions 89Zr and αVβ3 integrins targeting ability of cyclic c (RGDfC) peptide was employed to construct an efficient nanoplatform. And we evaluated the feasibility of 89Zr-RGD-MNP PET/PAI of αVβ3 expression in vivo and in vitro. Methods We conjugated αVβ3 integrins, cyclic c (RGDfC) peptide, to MNP and chelated the long-lived positron-emitting nuclide 89Zr. The bio-stability and targeting action was detected in macrophages. And the PET/PAI imaging was performed in apoE−/− mice with partial carotid ligation leading to atherosclerosis. In PET imaging, tracer uptake was measured in the stenotic areas of the carotid arteries, as well as on the contralateral side at different time points in vivo. In PAI, photoacoustic signal was measured in the atherosclerosis of the carotid arteries in vivo. Melanin staining and immunohistochemistry of αVβ3 expression were detected in atherosclerosis of the carotid arteries. Results 89Zr-RGD-MNP showed excellent bio-stability and targeting action. PET imaging showed specific tracer accumulation at plaques in the left carotid artery, confirmed by competitive receptor blocking studies and the contrast in the right carotid artery. In the biodistribution studies, the left carotid (5.29%±0.78%) showed higher uptake than the right carotid (2.11%±1.55%). PAI showed the PA signal in the surgery group (452±85 a.u.) were stronger than the control (156±45 a.u.) and blocking group (254±66 a.u). The result was consistent with PET imaging and the presence of nanoparticles, as indicated by pathological examinations. These results presented good in vivo multimodality imaging (PET/PAI) properties. Conclusions We have developed 89Zr-labeled atherosclerotic plaques imaging agents based on the natural melanin nanoparticle. 89Zr-RGD-MNP demonstrates specific tracer accumulation in mice atherosclerotic carotid plaques. In this model, its uptake was associated with αVβ3 expression. 89Zr-RGD-MNP is a potential tracer for noninvasive imaging in atherosclerosis. Acknowledgement/Funding National Natural Science Foundation of China 81770452, 81470401

Development of novel dapagliflozin loaded solid self-nanoemulsifying oral delivery system: Physiochemical characterization and in vivo antidiabetic activity

Self-nanoemulsifying drug delivery system (SNEDDS) is one of the most promising nanoplatforms to enhance the oral efficacy of poorly-bioavailable therapeutics. The present study aimed to develop solid-SNEDDS (S-SNEDDS) for oral delivery of dapagliflozin. Dapagliflozin loaded SNEDDS was developed using eucalyptus oil, tween 80 and PEG 400 as the formulation components and then converted to S-SNEDDS using the biocompatible adsorbent avicel PH-101. The droplet size of SNEDDS and reconstituted S-SNEDDS was found to be 65.23 ± 5.54 nm and 74.23 ± 3.86 nm with negative zeta potential, respectively. The in-vitro drug release studies revealed that the release dapagliflozin was better from S-SNEDDS (93.79 ± 2.23% in 1 h) as compared to the pure drug (38.33 ± 1.78%) and exhibited zero order release kinetics. Solid-state characterization of S-SNEDDS revealed that dapagliflozin was compatible with formulation components and was converted in amorphous state inside S-SNEDDS. Moreover, dapagliflozin loaded SNEDDS and S-SNEDDS exhibited significantly higher hypoglycaemic effect in diabetic albino rats as compared to pure drug. Therefore, our findings strongly suggest that developed S-SNEDDS could serve as an efficient nanoplatform for oral delivery of dapagliflozin for better management of diabetes mellitus.

Galvanic exchange-induced growth of Au nanocrystals on CuS nanoplates for imaging guided photothermal ablation of tumors

The conventional methods for constructing CuS-Au heterostructures in aqueous solution require the assistance of reducing agents such as NaBH4. Herein, without the additional reducing agent, we found that CuS nanoplates can be used as efficient nanoplatform and reducing agent for constructing CuS-Au heterostructures through the galvanic exchange route. The CuS-Au heterostructures were prepared by facilely introducing CuS nanoplates into HAuCl4 solution with continuous stirring, and the size (10–45 nm) and the number (1–3) of Au nanocrystals on CuS nanoplate were controlled by adjusting the Au/Cu molar ratios and stirring time. The obtained CuS-Au heterostructures possessed strong localized plasmon resonances (LSPRs) absorption in the near infrared (NIR) region, endowing them with the rapid photothermal response and high photothermal conversion efficiency of 36.5%. Moreover, due to the high atomic number of Au element, CuS-Au heterostructures were capable of high X-ray attenuation coefficient for X-ray computed tomography (CT) imaging. When CuS-Au dispersion was injected into the tumor of mice, the tumor could be monitored by CT and thermal imaging, and then thermally eradicated under the irradiation of 1064 nm laser. Therefore, the CuS-Au heterostructures were simply synthesized through the galvanic exchange route and served as efficient nanoagent for tumor theranostics.

Verteporfin-loaded mesoporous silica nanoparticles inhibit mouse melanoma proliferation in vitro and in vivo

Melanoma is one of the most lethal tumors among the skin cancers, arising from complex genetic mutations in melanocyte. Melanoma microenvironment is very heterogeneous, showing complex vascular networks and immunogenicity, as well as induced acquired resistance to treatments by upregulation of multidrug resistance (MDR) mechanisms. Different studies have showed that Photodynamic Therapy (PDT) could be considered a new potential approach for melanoma treatment. PDT combines a light with a specific wavelength and a photosensitizer: when these two elements interact reactive oxygen species (ROS) are generated leading to tumor cell destruction. In this study verteporfin (Ver), a second-generation photosensitizer, has been conjugated with mesoporous silica nanoparticles (MSNs): the resulting Ver-MSNs are an efficient nanoplatforms used to enhance cargo capacity and cellular uptake. Our in vitro and in vivo studies investigated whether Ver-MSNs were able to reduce or inhibit melanoma growth. In vitro experiments performed using B16F10 mouse melanoma cells showed that Ver-MSNs stimulated by red light (693 nm) significantly decreased in vitro cells proliferation in a range of concentration between 0.1 μg/ml to 10 μg/ml. When Ver-MSNs (5 μg/ml in glycerol) were topically administrated to melanoma tumor mass developed in mice and stimulated by red light for four times in 16 days, they were able to reduce the tumor mass of 50.2 ± 6,6% compared to the untreated (only glycerol) mice. In the light of this information, PDT performed using Ver-MSNs could be considered a new promising and potential approach to treat melanoma.

Light-Controlled Generation of Singlet Oxygen within a Discrete Dual-Stage Metallacycle for Cancer Therapy.

Noninvasive control over the reversible generation of singlet oxygen (1O2) has found the practical significance in benefiting photodynamic therapy. In this study, we developed a new dual-stage metallacycle (M) by using a photosensitizer and photochromic switch as the functional building blocks, which enables the noninvasive "off-on" switching of 1O2 generation through the efficient intramolecular energy transfer. Due to the proximal placement of the functional entities within the well-defined metallacyclic scaffold, 1O2 generation in the ring-closed form state of the photochromic switch (C-M) is quenched by photoinduced energy transfer, whereas the generation of 1O2 in the ring-open form state (O-M) is activated upon light irradiation. More interestingly, the metallacycle-loaded nanoparticles with relatively high stability and water solubility were prepared, which allow for the delivery of metallacycles to cancer cells via endocytosis. Their theranostic potential has been systematically investigated both in vitro and in vivo. Under the light irradiation, the designed ring-open form nanoparticles (O-NPs) show remarkable higher cytotoxicity against cancer cells compared to the ring-closed form nanoparticles (C-NPs). In vivo experiments also revealed that tumors can be very efficiently eliminated by the designed nanoparticles under light irradiation with the ability to regulate in vivo generation of singlet oxygen. All these results demonstrated that the supramolecular coordination complexes with a dual-stage state provide a highly efficient nanoplatform for noninvasive control over the reversible generation of 1O2, thus allowing for their promising applications in tumor treatment and beyond.

Hyaluronic Acid-Decorated Laponite® Nanocomposites for Targeted Anticancer Drug Delivery.

In this study, hyaluronic acid (HA), a natural polysaccharide that can specifically bind to CD44 receptors, was conjugated onto laponite® (LAP) nanodisks for the encapsulation and specific delivery of the anti-cancer drug doxorubicin (DOX) to CD44-overexpressed cancer cells. The prepared LM-HA could encapsulate DOX efficiently and release drug in a continuous manner with pH-responsiveness. In vitro cell viability assay proved that LM-HA had good biocompatibility, and drug-loaded LM-HA/DOX exhibited targeted anti-tumor effects against HeLa cells with CD44 receptors overexpressed. In addition, the flow cytometric detection and confocal laser scanning microscope results confirmed that LM-HA/DOX could be specifically internalized by HeLa cells via CD44-mediated endocytosis. Therefore, the HA-modified LAP nanodisks with high drug loading efficiency, pH-sensitive drug release properties and CD44 targetability might be an efficient nanoplatform for cancer chemotherapy.

Decorating protein nanospheres with lactoferrin enhances oral COX-2 inhibitor/herbal therapy of hepatocellular carcinoma.

Lactoferrin (LF)-targeted gliadin nanoparticles (GL-NPs) were developed for targeted oral therapy of hepatocellular carcinoma. Celecoxib and diosmin were incorporated in the hydrophobic matrix of GL-NPs whose surface was decorated with LF by electrostatic interaction for binding to asialoglycoprotein receptors overexpressed by liver cancer cells. Targeted GL-NPs showed enhanced cytotoxic activity and increased cellular uptake in liver tumor cells compared with nontargeted NPs. Moreover, they demonstrated superior in vivo antitumor effects including reduction in the expression levels of tumor biomarkers and induction of caspase-mediated apoptosis. Ex vivo imaging of isolated organs exhibited extensive accumulation of NPs in livers more than other organs. LF-targeted GL-NPs could be considered as an efficient nanoplatform for targeted oral drug delivery for liver cancer therapy.

Microenvironment-Responsive Magnetic Nanocomposites Based on Silver Nanoparticles/Gentamicin for Enhanced Biofilm Disruption by Magnetic Field.

Biofilms contribute to persistent bacterial infections as well as formidable resistances to conventional antibiotics. However, it is still a major challenge to establish an advanced antibacterial nanoplatform that can efficiently eradicate biofilms while overcoming bacterial resistances. Taking advantage of the stimuli-responsive technique and the magnetic guidance strategy, here we present a highly efficient nanoplatform for planktonic inactivation and biofilm disruption. The multilayer films consisting of antibiotic gentamicin (Gen), tannic acid, and silver nanoparticles (AgNPs) were fabricated and coated on magnetic nanoparticles via electrostatic interactions. To achieve controlled drug release and improved biocompatibility, biodegradable hyaluronic acid was capped on the outer surface as a responsive shell. In vitro release profiles suggested that the nanocomposites showed both enzyme and pH-responsive release properties. The nanoplatform could be employed as a powerful nanocarrier for small molecular Gen and AgNPs delivery and on-demand release in response to bacterial infection microenvironment. The nanocomposites also showed satisfying antibacterial capacities against planktonic Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli. Intriguingly, with magnetic field navigation (NdFeB, 2000 gauss), the nanocomposites could be guided to handily penetrate into S. aureus biofilm and performed dual-responsive release, showing significantly enhanced biofilm disruption. Moreover, excess reactive oxygen species production resulting from the nanocomposites contributed to the decomposition of biofilm matrix and ultimate biofilm eradication. As a consequence, the ingenious antibacterial nanoplatform could be promising for combating biofilm infections while overcoming bacterial resistances with extra environmental factors such as magnetic field.

Nanoscale Melittin@Zeolitic Imidazolate Frameworks for Enhanced Anticancer Activity and Mechanism Analysis.

The cytolytic peptide melittin (MLT) is an important candidate of anticancer drug owing to its hemolytic properties. Nevertheless, its clinical applications are severely restricted as a result of its nonspecific toxicities like hemolysis. In this work, we reported MLT-loaded zeolitic imidazolate framework-8 (MLT@ZIF-8) nanoparticles (NPs). The formed MLT@ZIF-8 NPs not only possess excellent stability but also efficiently inhibit the hemolysis bioactivity of MLT. Confocal scanning imaging and cytotoxicity experiments revealed that as-synthesized MLT@ZIF-8 NPs exhibit enhanced cellular uptake and cytotoxicity toward cancer cells compared to MLT. The mechanism is well investigated by a series of transcriptome analysis, which indicates that MLT@ZIF-8 NPs can regulate the expression of 3383 genes, and the PI3K/Akt-regulated p53 pathway is involved in MLT@ZIF-8 NPs induced A549 cells apoptosis. Finally, MLT@ZIF-8 NPs exhibit enhanced antitumor activity than free MLT in vivo, while no obvious systemic toxicity has been found. This work emphasizes the great potential of utilizing MOF as a simple and efficient nanoplatform for deliverying cytolytic peptides in cancer treatment, and also the investigation on the antitumor mechanism could provide theoretical support for clinical usage of MLT.

The shape effect of reconstituted high-density lipoprotein nanocarriers on brain delivery and Aβ clearance

Accumulation of extracellular β-amyloid (Aβ) is crucial for the pathogenesis of Alzheimer’s disease (AD), and the development of novel therapeutic agents that can both accelerate Aβ clearance and inhibit the subsequent pathological cascades is regarded as a promising strategy for AD management. In our previous study, we have constructed discoidal apolipoprotein E3–reconstituted high-density lipoprotein (ApoE3-rHDL) as an efficient nanoplatform that can penetrate the blood–brain barrier and accelerate Aβ clearance for a combination treatment of AD. To further improve its drug loading capacity, we hypothesized that spherical rHDL might serve as a more powerful nanocarrier if it has the same brain delivery and Aβ clearance abilities as the discoidal rHDL does. To evaluate the potential of spherical rHDL as a promising alternative for the combination therapy for AD, here, we investigated the effect of the shape of rHDL on its brain delivery, Aβ clearance, and anti-AD efficacy. We found that spherical rHDL had stronger Aβ-binding affinity than discoidal rHDL did, more effectively facilitated microglial uptake and degradation of Aβ1–42, achieved better brain distribution after intravenous administration, and more powerfully reduced Aβ deposition, decreased microglia activation, attenuated neurological damage, and rescued memory deficits in a mouse model of AD. Among the rHDLs evaluated, monosialotetrahexosyl ganglioside–incorporated spherical rHDL exerted the best effect. The findings of this study for the first time show a shape effect of an rHDL nanocarrier on its biological functions and suggest that a spherical lipoprotein-mimic nanocarrier may serve as a more efficient multifunctional nanoplatform for AD therapy.

Magnetofluorescent Fe3O4/carbon quantum dots coated single-walled carbon nanotubes as dual-modal targeted imaging and chemo/photodynamic/photothermal triple-modal therapeutic agents

In this work, PEG 2000N modified Fe3O4@carbon quantum dots (CQDs) coated single-walled carbon nanotubes (SWNTs) are fabricated and utilized as a multifunctional platform for imaging-guided collaborative treatment of cancer when the obtained agents act as dual photodynamic and photothermal effect under 808 nm laser irradiation. A model chemotherapy drug, doxorubicin (DOX), could be loaded into the pore structure of the obtained SWCNTs-PEG-Fe3O4@CQDs nano-carriers with high efficiency. These magnetofluorescent SWCNTs-PEG-Fe3O4@CQDs were conjugated with a sgc8c aptamer, denoted as SWCNTs-PEG-Fe3O4@CQDs-DOX-Apt, for targeting dual modalfluorescence/magnetic resonance (MR) imaging. Multifunctional SWCNTs-PEG-Fe3O4@CQDs-DOX-Apt had a strong effect on the targeted lung cancer cells, in the manner of inducing photodynamic and photothermal ablation, and was found to release DOX rapid following irradiation with pH/NIR laser. The current research demonstrates that SWCNTs-PEG-Fe3O4@CQDs-DOX-Apt nanocomposites can be used as an efficient nanoplatform for combing cancer photothermal therapy (PTT), photodynamic therapy (PDT) and chemotherapy (CT).

Octopod PtCu Nanoframe for Dual-Modal Imaging-Guided Synergistic Photothermal Radiotherapy.

Heavy atom nanoparticles have high X-ray absorption capacity and near infrared (NIR) photothermal conversion efficiency, which could be used as radio-sensitizers. We hypothesized that concave PtCu octopod nanoframes (OPCNs) would be an efficient nanoplatform for synergistic radio-photothermal tumor ablation.Methods: In this study, we newly exploited a folic acid-receptor (FR) mediated photothermal radiotherapy nanoagent base on OPCNs. OPCNs were synthesized with a hydrothermal method and then modified with polyethylene glycol (PEG) and folic acid (FA). A series of physical and chemical characterizations, cytotoxicity, targeting potential, endocytosis mechanism, biodistribution, systematic toxicological evaluation, pharmacokinetics, applications of OPCNs-PEG-FA for in vitro and in vivo infrared thermal imaging (ITI)/photoacoustic imaging (PAI) dual-modal imaging and synergistic photothermal radiotherapy against tumor were carried out.Results: The OPCNs-PEG-FA demonstrated good biocompatibility, strong NIR absorption and X-ray radio-sensitization, which enabling it to track and visualize tumor in vivo via ITI/PAI dual-modal imaging. Moreover, the as-synthesized OPCNs-PEG-FA exhibited remarkable photothermal therapy (PTT) and radiotherapy (RT) synergistic tumor inhibition when treated with NIR laser and X-ray.Conclusion: A novel multifunctional theranostic nanoplatform based on OPCNs was designed and developed for dual-modal image-guided synergistic tumor photothermal radiotherapy.

Photo‐Induced Charge‐Variable Conjugated Polyelectrolyte Brushes Encapsulating Upconversion Nanoparticles for Promoted siRNA Release and Collaborative Photodynamic Therapy under NIR Light Irradiation

AbstractCombination of photodynamic therapy (PDT) with small interfering RNA (siRNA) therapy has become a major strategy in cancer treatment for enhancing anticancer efficacy. However, developing nanoplatform that can promote siRNA release and collaborate with efficient PDT under NIR light irradiation is still a big challenge. Photo‐induced charge‐variable conjugated polyelectrolyte brushes encapsulating upconversion nanoparticles (UCNP@CCPEB) as an efficient nanoplatform are reported. Cationic conjugated polyelectrolyte brush (CCPEB) is synthesized through quaternary ammoniation of N‐functionalized polyfluorene brush by photodegradable 2‐nitrobenzyl‐2‐bromoacetate. CCPEB with abundant positive charges and intrinsic photosensitizer (PS) performance is good for integrating siRNA carrier and PS into one molecule. The obtained CCPEB next encapsulates upconversion nanoparticle for realizing its NIR light excitation. Agarose gel electrophoresis experiments show that UCNP@CCPEB present good stability and excellent siRNA‐loading capacity (1 mol UCNP@CCPEB to at least 32.5 mol siRNA). Under 980 nm light irradiation, UCNP@CCPEB exhibit efficient single oxygen production for PDT. Concurrently, the photoresponsive cationic side‐chain of CCPEB turns into zwitterionic chain and thus accelerates its siRNA release to 80%. In vitro and in vivo experiments show that the successful A549 tumor suppression is achieved by UCNP@CCPEB/siPlk1 complex under 980 irradiation. It is envisioned that UCNP@CCPEB can serve as an efficient platform for combining various phototherapies together.

Mesoporous composite nanoparticles for dual-modality ultrasound/magnetic resonance imaging and synergistic chemo-/thermotherapy against deep tumors.

High-intensity focused ultrasound (HIFU) is a promising and noninvasive treatment for solid tumors, which has been explored for potential clinical applications. However, the clinical applications of HIFU for large and deep tumors such as hepatocellular carcinoma (HCC) are severely limited by unsatisfactory imaging guidance, long therapeutic times, and damage to normal tissue around the tumor due to the high power applied. In this study, we developed doxorubicin/perfluorohexane-encapsulated hollow mesoporous Prussian blue nanoparticles (HMPBs-DOX/PFH) as theranostic agents, which can effectively guide HIFU therapy and enhance its therapeutic effects in combination with chemotherapy, by decreasing the cavitation threshold. We investigated the effects of this agent on ultrasound and magnetic resonance imaging in vitro and in vivo. In addition, we showed a highly efficient HIFU therapeutic effect against HCC tumors, as well as controlled drug release, owing to the phase-transitional performance of the PFH. We therefore conclude that HMPB-DOX/PFH is a safe and efficient nanoplatform, which holds significant promise for cancer theranostics against deep tumors in clinical settings.

Porous NH2-MIL-125 as an efficient nano-platform for drug delivery, imaging, and ROS therapy utilized Low-Intensity Visible light exposure system

Metal-organic frameworks are a novel class of organic-inorganic hybrid polymer with potential applications in bioimaging, drug delivery, and ROS therapy. NH2-MIL-125, which is a titanium-based metal organic framework with a large surface area of 1540m2/g, was synthesized using a hydrothermal method. The material was characterized by powder X-ray diffreaction (PXRD), thermogravimetric analysis (TGA), and transmission electron microscopy (TEM), and N2 isotherm analyses. The size of the polymer was reduced to the nanoscale using a high-frequency sonication process. PEGylation was carried out to improve the stability and bioavailability of the NMOF. The as-synthesized nano-NH2-MIL-125/PEG (NMOF/PEG) exhibited good biocompatibility over the (Cancer) MCF-7 and (Normal) COS-7 cell line. The interaction of NMOF/PEG with the breast cancer cell line (MCF-7) was examined by BIO-TEM analysis and laser confocal imaging. 2′,7′–dichlorofluorescin diacetate (DCFDA) analysis confirmed that NMOF/PEG produced free radicals inside the cancer cell line (MCF-7) upon visible light irradiation. NMOF/PEG absorbed a large amount of DOX (20wt.% of DOX) and showed pH, and photosensitive release. This controlled drug delivery was attributed to the presence of NH2, Ti group in MOF and a hydroxyl group in PEG. This combination of chemo- and ROS-therapy showed excellent efficiency in killing cancer MCF-7 cells.

Cell to rodent: toxicological profiling of folate grafted thiomer enveloped nanoliposomes.

Polymeric nanomaterials, hybridized with lipid components, e.g. phosphocholine or fatty acids, are currently being explored for efficient nano-platforms for hydrophobic drugs. However, their toxicology and toxicokinetics need to be established before enabling their clinical potential. The aim of this study was to investigate the toxicological profile of thiomer enveloped hybrid nanoliposomes (ENLs) and bare nanoliposomes (NLs), loaded with docetaxel (DTX) hydrophobic drug, biocompatible nano-carriers for therapeutic cargo. The in vitro toxicity of hybrid ENLs and NLs was evaluated towards the HCT-116 colon cancer cell line. Biocompatibility was explored against macrophages and acute oral toxicity was examined in mice for 14 days. The anticancer IC50 for ENLs was 0.148 μg ml-1 compared with 2.38 μg ml-1 for pure docetaxel (DTX). The human macrophage viability remained above 65% and demonstrated a high level of biocompatibility and safety of ENLs. In vivo acute oral toxicity showed slight changes in serum biochemistry and haematology but no significant toxicities were observed referring to the safety of DTX loaded hybrid ENLs. On histological examination, no lesions were determined on the liver, heart and kidney. These studies showed that hybrid ENLs can serve as a safe and biocompatible platform for oral delivery of hydrophobic drugs.

Ruthenium nitrosyl functionalized graphene quantum dots as an efficient nanoplatform for NIR-light-controlled and mitochondria-targeted delivery of nitric oxide combined with photothermal therapy.

A mitochondria-targeting nanoplatform for near-infrared-light-controlled release of nitric oxide accompanied by photothermal therapy was developed, which consists of ruthenium nitrosyl functionalized N-doped graphene quantum dots and a triphenylphosphonium moiety. The nanoplatform demonstrated both in vitro and in vivo anti-tumor efficacy upon irradiation with 808 nm light.

Single‐Layer MoS2 Nanosheets with Amplified Photoacoustic Effect for Highly Sensitive Photoacoustic Imaging of Orthotopic Brain Tumors

Photoacoustic (PA) imaging, as a fast growing technology that combines the high contrast of light and large penetration depth of ultrasound, has demonstrated great potential for molecular imaging of cancer. However, PA molecular imaging of orthotopic brain tumors is still challenging, partially due to the limited options and insufficient sensitivity of available PA molecular probes. Here, the direct formation of single‐layer (S‐MoS2), few‐layer (F‐MoS2), and multi‐layer (M‐MoS2) nanosheets by the albumin‐assisted exfoliation without further surface modifications is reported. It is demonstrated that the PA effect of the MoS2 nanosheets is highly dependent on their layered nanostructures. Decreasing the number of nanosheet layers from M‐MoS2 to S‐MoS2 can both significantly enhance the near‐infrared light absorption and improve the elastic properties of the nanomaterial, resulting in greatly amplified PA effect. The in vitro experiments demonstrate that the prepared S‐MoS2 with excellent biocompatibility can be efficiently internalized into U87 glioma cells, producing strong PA signals for highly sensitive detection of brain tumor cells, with a detection limit of ≈100 cells. Intravenous administration of S‐MoS2 to both U87 subcutaneous and orthotopic tumor‐bearing mice shows highly efficient tumor retention and significantly enhanced PA contrast. Tumor tissue ≈1.5 mm below the skull can still be clearly visualized in vivo. Previous studies suggest that the fabricated S‐MoS2 with amplified PA effect have high potential to serve as an efficient nanoplatform for sensitive PA molecular imaging and hold promising prospect for translational medicine.

Verteporfin based silica nanoplatform for photodynamic therapy

A highly efficient nanoplatform for photodynamic therapy was obtained by covalent conjugation of verteporfin with mesoporous silica nanoparticles. Verteporfin has an intense absorption band in the red region of the Vis spectrum ensuring a deeper tissue penetration; this feature makes verteporfin-based formulations particularly attractive for in vivo PDT applications. The verteporfin loading, dispersion and efficiency in the photoproduction and delivery of singlet oxygen (1O2) were carefully evaluated. In vitro tests have evidenced that the optimized nanoplatform is able to largely reduce HeLa cell proliferation after red-light irradiation.