DNA polymer films used as drug delivery systems to early-stage diagnose and treatment of breast cancer using 3D tumor spheroids as a model.

The present study examines the design of DNA polymeric films (DNA-PFs) associated with aluminum chloride phthalocyanine (AlClPc) (DNA-PFs-AlClPc), as a promising drug delivery system (DDS), applicable for breast cancer treatment and early-stage diagnosis using photodynamic therapy (PDT). This study starts evaluating (MCF7) as a model for breast cancer cell behavior associated with DNA-PFs. Analyses of the morphological behaviors, biochemical reaction, and MCF7 cell adhesion profile on DNA-PFs were evaluated. SEM and AFM analysis allowed the morphological characterization of the DNA-PFs. Cell viability and cell cycle kinetics studies indicate highly biocompatible material capable of anchoring MCF7 cells, allowing the attachment and support of cell in the same structure where the insertion of AlClPc (DNA-PFs-AlClPc). The application of visible light photoactivation based on classical PDT protocol over the DNA-PFs-AlClPc showed a reduction in cell viability with increased cell death proportional to the fluency energy range from 600, 900, and 1800 mJ cm-2. The 3D organoid system mimics the tumor microenvironment which was precisely observed in human breast cancer in early-stage progression in the body. The results observed indicate that the viability was reduced by more than 80% in monolayer culture and around 50% in the 3D organoid cell culture at the highest energy fluency (1800 mJ cm-2). With low energy fluency (100 mJ cm-2,), the DNA-PFs-AlClPc did not show a cytotoxic effect on MCF7 cells, enabling the potential for photodiagnosis of early-stage human breast cancer detection in the initial stage of progression.

Single-Atom Gadolinium Anchored on Graphene Quantum Dots as a Magnetic Resonance Signal Amplifier.

A single-atom metal doped on carbonaceous nanomaterials has attracted increasing attention due to its potential applications as high-performance catalysts. However, few studies focus on the applications of such nanomaterials as nanotheranostics for simultaneous bioimaging and cancer therapy. Herein, it is pioneeringly demonstrated that the single-atom Gd anchored onto graphene quantum dots (SAGd-GQDs), with dendrite-like morphology, was successfully prepared. More importantly, the as-fabricated SAGd-GQDs exhibits a robustly enhanced longitudinal relaxivity (r1 = 86.08 mM-1 s-1) at a low Gd3+ concentration of 2 µmol kg-1, which is 25 times higher than the commercial Gd-DTPA (r1 = 3.44 mM-1 s-1). In vitro and in vivo studies suggest that the obtained SAGd-GQDs is a highly potent and contrast agent to obtain high-definition MRI, thereby opening up more opportunities for future precise clinical theranostics.

Biocompatible HA@Fe3 O4 @N-CDs hybrids for detecting and absorbing lead ion.

The trinary hydroxyapatite@Fe3 O4 @N-doped carbon dots (HA@Fe3 O4 @N-CDs) hybrids were prepared by one-pot hydrothermal approach and utilized to detect and remove lead ion from aqueous solution. The structures and morphologies of as-obtained nanorod-like HA@Fe3 O4 @N-CDs hybrids were characterized by X-ray diffraction, scanning electron microscopy, and X-ray photoelectron spectroscopy measurements. These HA@Fe3 O4 @N-CDs hybrids possess good magnetism by magnetic hysteresis test and multi-colored fluorescence by the CLSM measurement. Furthermore, the as-obtained hybrids display excellent biocompatibility by MTT assay. Importantly, the trinary magnetic HA@Fe3 O4 @N-CDs hybrids as a green detector and adsorbent of Pb2+ were investigated. The influence of the different pH, the concentration of heavy metal, and the maximum adsorption capacity on removal efficiency was measured in detail. The maximum Pb2+ adsorption capacity on HA@Fe3 O4 @N-CDs hybrids is 450 mg/g. The kinetic mechanism was a pseudo-second order model, and the isotherm data was fitted well by the Langmuir isotherm and Freundlich model. Hence, the nanorod-like HA@Fe3 O4 @N-CDs hybrids could be a multifunctional material with significant potential applications in heavy metal detection and adsorption, bone tissue regeneration, magnetic therapy, and biomedicine. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2019.

Fluorescent CDs@PCL hybrids via tartaric acid, CDs-cocatalyzed polymerization.

In this paper, the environment-friendly, water-soluble carbon dots (CDs) with stable photoluminescence (PL) have been prepared via the one-step pyrolysis of lotus leaf. Then the as-prepared CDs containing abundant hydroxylic and carboxylic groups were employed as cocatalyst with tartaric acid (TA) in ring-opening polymerization (ROP) of ε-caprolactone (ε-CL). The low-toxic organic acid TA, as main catalyst, was used to catalyze the ROP of ε-CL efficiently. The fluorescent CDs@PCL hybrids were obviously hydrophobic and they exhibited an excellent biocompatibility, and biodegradability due to the existence of PCL. Therefore the hydrophobic, biodegradable and multi-color fluorescent CDs@PCL hybrids may have potential applications in biomedicine, photocatalyst, bioimaging, and environmental analysis. Furthermore the application of CDs in catalyzing and initiating polymerization reaction will exemplify the versatility of CDs in the most unexpected fields.

Cu2+-Complex of hydrophilic nitrogen-rich polymer dots applied as a new MRI contrast agent.

We report on a novel Cu2+-complex of nitrogen-rich polymer dots for magnetic resonance imaging (MRI). The N-rich polymer dots are prepared from N-vinyl imidazole (VIm) by a one-pot hydrothermal synthesis at 220 °C (24 h) and used later on to fabricate a Cu2+-PVIm dot complex via efficient incorporation of Cu2+ into aqueous medium. The obtained Cu2+-PVIm dot complexes display relaxivity (r1 = 1.05 mM-1 s-1) two times higher than Cu2+ in aqueous solution (r1 = 0.43 mM-1 s-1) and three times higher than Cu2+ in aqueous solution coordinated with VIm monomers (r1 = 0.32 mM-1 s-1), which show a remarkable contrast enhancement for T1-weighted MRI while efficiently labeling MCF-7 cells and other biomedical applications.

Trackable Mitochondria-Targeting Nanomicellar Loaded with Doxorubicin for Overcoming Drug Resistance.

Multidrug resistance (MDR) has been recognized as a major obstacle to successful chemotherapy for cancer in the clinic. In recent years, more and more nanoscaled drug delivery systems (DDS) are constructed to modulate drug efflux protein (P-gp) and deliver chemotherapeutic drugs for overcoming MDR. Among them, d-α-tocopheryl polyethylene glycol succinate (TPGS) has been widely used as a drug carrier due to its capability of inhibiting overexpression of P-gp and good amphiphilicity favorable for improving permeation and long-circulation property of DDS. In the present work, a novel kind of mitochondria-targeting nanomicelles-based DDS is developed to integrate chemotherapeutics delivery with fluorescence imaging functionalities on a comprehensive nanoplatform. The mitochondria-targeting nanomicelles are prepared by self-assembly of triphenylphosphine (TPP)-modified TPGS and fluorescent carbon quantum dots (CQDs) in an n-hexane/H2O mixed solution, named CQDs-TPGS-TPP. Notably, although the drug loading content of doxorubicin (DOX) in the as-prepared nanomicelles is as low as 3.4%, the calculated resistant index (RI) is greatly decreased from 66.23 of free DOX to 7.16 of DOX-loaded nanomicelles while treating both parental MCF-7 cells and drug-resistant MCF-7/ADR cells. Compared with free DOX, the penetration efficiency of DOX-loaded nanomicelles in three-dimensional multicellular spheroids (MCs) of MCF-7/ADR is obviously increased. Moreover, the released DOX from the nanomicelles can cause much more damage to cells of drug-resistant MCs. These results demonstrate that our constructed mitochondria-targeting nanomicelles-based DDS have potential application in overcoming MDR of cancer cells as well as their MCs that mimic in vivo tumor tissues. The MDR-reversal mechanism of the DOX-loaded CQDs-TPGS-TPP nanomicelles is also discussed.

Multifunctional copolymer coating of polyethylene glycol, glycidyl methacrylate, and REDV to enhance the selectivity of endothelial cells.

Multifunctional polymer coatings have potential applications in biomaterials. These coatings possess reactive functional groups for the immobilization of specific biological factors that can influence cellular behavior. These coatings also display low nonspecific protein adsorption. In this study, we prepared a multifunctional polymer coating through the deposition of random copolymers of poly(ethylene glycol) methacrylate (PEGMA) and glycidyl methacrylate (GMA) to prevent nonspecific attachment and enable the covalence of Arg-Glu-Asp-Val (REDV) peptide with endothelial cells (ECs) selectivity. Coatings were characterized by X-ray photoelectron spectroscopy (XPS). The adhesion and proliferation of ECs and smooth muscle cells (SMCs) onto the REDV-modified surface were investigated to understand the synergistic action of antifouling PEG and EC selective REDV peptide conjugated GMA. The copolymers containing GMA and PEG groups are very useful as a multifunctional coating material with anti-fouling and ECs specific adhesion for implant materials surface modification.

Horseradish peroxidase-immobilized magnetic mesoporous silica nanoparticles as a potential candidate to eliminate intracellular reactive oxygen species.

Horseradish peroxidase-immobilized magnetic mesoporous silica nanoparticles (MMSNs-HRP) have been synthesized by a NHS/EDC coupling between the amino groups of horseradish peroxidase (HRP) and the carboxyl groups on the MMSNs surface. It is found that the immobilized HRP on MMSNs still retain high activity and the MMSNs-HRP can eliminate the reactive oxygen species (ROS) in Chinese hamster ovary (CHO) cells induced by the addition of H2O2 aqueous solution. Further, the fluorescent MMSN-HRP-CD nanoparticles have been prepared by attaching biocompatible, fluorescent carbon dots (CDs) to MMSNs-HRP. We have also investigated the effect of an applied magnetic field on cellular uptake of MMSNs-HRP-CDs and found that the internalization of MMSNs-HRP-CDs by CHO cells could be enhanced within 2 hours under the magnetic field. This work provides us with a novel and efficient method to eliminate ROS in living cells by using HRP-immobilized nanoparticles.

Preparation, characterization, and drug release behaviors of drug nimodipine-loaded poly(epsilon-caprolactone)-poly(ethylene oxide)-poly(epsilon-caprolactone) amphiphilic triblock copolymer micelles.

Amphiphilic triblock copolymers, poly(epsilon-caprolactone)-poly(ethylene oxide)-poly(epsilon-caprolactone) (PCL-PEO-PCL), were synthesized by ring opening polymerization of epsilon-caprolactone initiated with the hydroxyl functional groups of poly(ethylene glycol) at both ends of the chain. The micelles composed of this type of copolymer had such a structure that both ends of the PEO chain were anchored to the micelle. The critical micelle concentration of the block copolymer in distilled water was determined by a fluorescence probe technique using pyrene. As the hydrophobic components of the block copolymer increased, the critical micelle concentration value decreased. To estimate the feasibility as novel drug carriers, the block copolymer micelles were prepared by precipitation of polymer from acetone solution into water. From the observation of transmission electron microscopy, the micelles exhibited a spherical shape. Nimodipine was incorporated into the hydrophobic inner core of micelles as a lipophilic model drug to investigate the drug release behavior. The PEO/PCL ratio of copolymer was a main factor in controlling micelle size, drug-loading content, and drug release behavior. As PCL weight ratio increased, the micelle size and drug-loading content increased, and the drug release rate decreased.