Near-Infrared-Absorbing B-N Lewis Pair-Functionalized Anthracenes: Electronic Structure Tuning, Conformational Isomerism, and Applications in Photothermal Cancer Therapy.

B-N-fused dianthracenylpyrazine derivatives are synthesized to generate new low gap chromophores. Photophysical and electrochemical, crystal packing, and theoretical studies have been performed. Two energetically similar conformers are identified by density functional theory calculations, showing that the core unit adopts a curved saddle-like shape (x-isomer) or a zig-zag conformation (z-isomer). In the solid state, the z-isomer is prevalent according to an X-ray crystal structure of a C6F5-substituted derivative (4-Pf), but variable-temperature nuclear magnetic resonance studies suggest a dynamic behavior in solution. B-N fusion results in a large decrease of the HOMO-LUMO gap and dramatically lowers the LUMO energy compared to the all-carbon analogues. 4-Pf in particular shows significant absorbance at greater than 700 nm while being almost transparent throughout the visible region. After encapsulation in the biodegradable polymer DSPE-mPEG2000, 4-Pf nanoparticles (4-Pf-NPs) exhibit good water solubility, high photostability, and an excellent photothermal conversion efficiency of ∼41.8%. 4-Pf-NPs are evaluated both in vitro and in vivo as photothermal therapeutic agents. These results uncover B-N Lewis pair functionalization of PAHs as a promising strategy toward new NIR-absorbing materials for photothermal applications.

Recent Advance in Biological Responsive Nanomaterials for Biosensing and Molecular Imaging Application.

In recent decades, as a subclass of biomaterials, biologically sensitive nanoparticles have attracted increased scientific interest. Many of the demands for physiologically responsive nanomaterials in applications involving the human body cannot be met by conventional technologies. Due to the field's importance, considerable effort has been expended, and biologically responsive nanomaterials have achieved remarkable success thus far. This review summarizes the recent advancements in biologically responsive nanomaterials and their applications in biosensing and molecular imaging. The nanomaterials change their structure or increase the chemical reaction ratio in response to specific bio-relevant stimuli (such as pH, redox potentials, enzyme kinds, and concentrations) in order to improve the signal for biologically responsive diagnosis. We use various case studies to illustrate the existing issues and provide a clear sense of direction in this area. Furthermore, the limitations and prospects of these nanomaterials for diagnosis are also discussed.

Programmed Stimuli-Responsive Carbon Dot-Nanogel Hybrids for Imaging-Guided Enhanced Tumor Phototherapy.

For harmonizing the contradiction of nanotheranostic agents between enhanced tumor accumulation and penetration, efficient cell internalization and fast elimination are key tactics for promoting their clinical applications. Herein, programmed stimuli-responsive poly(N-isopropylacrylamide)-carbon dot (PNIPAM-CD) hybrid nanogels are designed to address the abovementioned conflicts. The enlarged particle size of PNIPAM-CDs enables one to effectively improve their accumulation at tumor sites. Once the hybrid nanogels are docked in tumors and exposed to deep-red-light (660 nm) irradiation, heat and reactive oxygen species (ROS) are generated from the CDs, consequently activating photothermal therapy (PTT) and photodynamic therapy (PDT) effects and meanwhile inducing partial degradation of PNIPAM-CDs for deep tissue penetration. Further, enhanced cellular internalization of the functional components can be achieved owing to the pH-responsive charge reversal and temperature-dependent hydrophilic/hydrophobic conversion characteristics of PNIPAM-CDs. Finally, the overexpressed glutathione (GSH) in tumor cells would trigger further cleavage of the partially degraded hybrid nanogels, which is beneficial for their rapid clearance from the body. This work not only proposed a novel strategy to fabricate nanotheranostic agents using just a single functional component (i.e., the versatile CDs) to simplify the preparation process but also achieved effective delivery of agents into tumor cells by overcoming the multiple biological barriers to enhance therapeutic efficacy and decrease side effects.

Nanoscale covalent organic frameworks: from controlled synthesis to cancer therapy.

Covalent organic frameworks (COFs), as a new type of crystalline porous materials, mainly consist of light-weight elements (H, B, C, N and O) linked by dynamic covalent bonds to form periodical structures of two or three dimensions. As an attribute of their low density, large surface area, and excellent adjustable pore size, COFs show great potential in many fields including energy storage and separation, catalysis, sensing, and biomedicine. However, compared with metal organic frameworks (MOFs), the relatively large size and irregular morphology of COFs affect their biocompatibility and bioavailability in vivo, thus impeding their further biomedical applications. This Review focuses on the controlled design strategies of nanoscale COFs (NCOFs), unique properties of NCOFs for biomedical applications, and recent progress in NCOFs for cancer therapy. In addition, current challenges for the biomedical use of NCOFs and perspectives for further improvements are presented.

Preparation of graphene oxide (GO)/lanthanum coordination polymers for enhancement of bactericidal activity.

In this study, graphene oxide/lanthanum coordination polymer (GLCP) nanocomposites are prepared and their bactericidal activities against seven typical Pathogenic bacteria are evaluated. The GLCPs are fabricated through the electrostatic self-assembly of La ions on negatively charged graphene oxide (GO), followed by the stabilization of π-π stacking to ensure the formation of lanthanum coordination polymers on the GO surface. The morphologies and structures of the synthesized GLCPs are characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM), ultraviolet-visible (UV-vis) spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, X-ray photoelectron spectroscopy (XPS) and thermogravimetric analysis (TGA). Moreover, the bactericidal effects of the well-coordinated GLCPs are investigated using the zone of inhibition and flat colony counting methods, as well as by determining the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The five GLCPs synthesized in this study exhibit broad-spectrum antibacterial activities against seven typical Pathogenic bacteria. We believe that our study could serve as a starting point to prepare bactericidal materials for further applications.

A novel hybrid nanoadsorbent for effective Hg2+ adsorption based on zeolitic imidazolate framework (ZIF-90) assembled onto poly acrylic acid capped Fe3O4 nanoparticles and cysteine.

This research reports a new mercury adsorbent in which Fe3O4 as a core was embedded into the shell of ZIF-90 in a one-pot synthesis and the subsequent post synthesis modification (PSM) of its surface with cysteine covalently, via a Schiff's base reaction. Poly acrylic acid (PAA) was capped on the surface of nanoparticles to prevent agglomeration of the nanoparticles. In addition, -COOH groups of PAA coordinated with Zn2+ of ZIF-90 and this provided the platform for ZIF-90 to grow on the nanoparticles forming the core-shell structure. Based on the strong interactions between the thiol groups on the adsorbent and mercury ions as elucidated by the XPS analysis, the as-synthesized adsorbent showed selectivity for Hg2+. The sorbent exhibited high adsorption capacity of 900 mg g-1 towards Hg2+ as calculated at pH 4 and the adsorption kinetics followed pseudo-second-order kinetics model better. The Hg2+ loaded adsorbent was easily regenerated and it maintained about 70 % efficiency after the third use. Low-cost, readily available and green materials, facile preparation, efficient removal and the breakthrough in three times recyclability give the novel ZIF-90 based hybrid nanoadsorbent wide prospects in the field of environmental remediation as a good adsorbent for Hg2+ removal in wastewater.

One-pot synthesis of hollow PDA@DOX nanoparticles for ultrasound imaging and chemo-thermal therapy in breast cancer.

Constructing nanocarriers with high drug loading capacity is a challenge, which limits the effective delivery of drugs to solid tumors. Here, we reported a one-pot synthesis of hollow nanoparticles (NPs) encapsulated by doxorubicin (DOX) and modified with polydopamine (PDA) to form PDA@DOX NPs for breast cancer treatment. PDA@DOX NPs demonstrated exceptionally high capacity (53.16%) for loading DOX. In addition, when PDA@DOX NPs were administered systemically, they exhibited responsive aggregation in the tumor sites and demonstrated a good controlled release effect for DOX due to the weak acidic environment of the tumor sites and targeting near-infrared (NIR) light irradiation. The PDA outer layer absorbed the near-infrared (NIR) light and facilitated simultaneous generation of heat energy for destroying the tumor cells to release the drug upon NIR irradiation. Moreover, this NIR-activated combined/synergistic therapy exhibited remarkably complete tumor growth suppression in a breast cancer mouse model. Importantly, NPs exhibited a good ultrasound performance both in vitro and in vivo, which could monitor the treatment process. In conclusion, this NIR-activated PDA@DOX NP system is demonstrated as a good US-guided combination (chemotherapy + PTT) therapy platform with high loading capacity and controlled drug release characteristics, which is promising for the treatment of breast cancer.

Dual ATP and pH responsive ZIF-90 nanosystem with favorable biocompatibility and facile post-modification improves therapeutic outcomes of triple negative breast cancer in vivo.

Zeolitic imidazole frameworks (ZIFs) are becoming a notable nanosystem in biomedicine field, due to their unique properties of favorable biocompatibility, pH-responsive degradable structure and high drug loading. Compared with the increasing attention on ZIF-8 in cancer diagnosis and treatment, there is limited research about the bio-application of ZIF-90, especially its in vivo therapeutic efficacy and related toxicity. Here, we synthesize nano ZIF-90 through a fast self-assembling process, and the synthesized nano ZIF-90 is about 75 nm with a negative zeta potential, providing better mitochondria targetability, cell biocompatibility and in vivo survival rate comparing to nano ZIF-8. To further explore the applicability of ZIF-90 in cancer treatment, a facile post-modification is used to conjugate Y1 receptor ligand [Asn6, Pro34]-NPY (AP) on the surface of doxorubicin (DOX)-encapsulated nano ZIF-90. AP-ZIF-90 significantly reduces premature DOX release at physiological pH level, and triggers more effective and faster DOX release inside the tumor cells with dual responsive to high adenosine triphosphate (ATP) and low pH condition. Combining targeted delivery and dual responsive release of DOX significantly improves the therapeutic efficacy of AP-ZIF-90@DOX in MDA-MB-231 tumor bearing mouse, and results in 80% survival rate over 40 days of treatment. At the given dosage, nano ZIF-90 is with excellent biocompatibility in vivo, inducing minimal side effect on the liver and renal functions. Therefore, nano ZIF-90 combines with Y1 receptor ligand with favorable biocompatibility and dual responsiveness can be used as a promising nanosystem for targeted triple negative breast cancer treatment in vivo.

pH protective Y1 receptor ligand functionalized antiphagocytosis BPLP-WPU micelles for enhanced tumor imaging and therapy with prolonged survival time.

Nanoparticle-based tumor therapies are extensively studied; however, few are capable of improving patient survival time due to premature drug leakage, off target effects, and poor tissue penetration. Previously, we successfully synthesized a novel family of Y1 receptor (Y1R) ligand modified, photoluminescent BPLP nanobubbles and nanoparticles for targeted breast cancer ultrasound imaging; however, increased accumulation could also be observed in the liver, kidney, and spleen, suggesting significant interaction of the particles with macrophages in vivo. Herein, for the first time, we imparted antiphagocytosis capability to Y1R ligand functionalized BPLP-WPU polymeric micelles through the incorporation of a CD47 human glycoprotein based self-peptide. Application of self-peptide modified, DOX loaded micelles in vivo resulted in a 100% survival rate and complete tumor necrosis over 100 days of treatment. In vivo imaging of SPION loaded, self-peptide modified micelles revealed effective targeting to the tumor site while analysis of iron content demonstrated reduced particle accumulation in the liver and kidney, demonstrating reduced macrophage interaction, as well as a 2-fold increase of particles in the tumor. As these results demonstrate, Y1R ligand, self-peptide modified BPLP-WPU micelles are capable of target specific cancer treatment and imaging, making them ideal candidates to improve survival rate and tumor reduction clinically.