Rotor-based image-guided therapy of glioblastoma.

Glioblastoma (GBM), deep in the brain, is more challenging to diagnose and treat than other tumors. Such challenges have blocked the development of high-impact therapeutic approaches that combine reliable diagnosis with targeted therapy. Herein, effective cyanine dyes (IRLy) with the near-infrared two region (NIR-II) adsorption and aggregation-induced emission (AIE) have been developed via an "extended conjugation & molecular rotor" strategy for multimodal imaging and phototherapy of deep orthotopic GBM. IRLy was synthesized successfully through a rational molecular rotor modification with stronger penetration, higher signal-to-noise ratio, and a high photothermal conversion efficiency (PCE) up to ∼60%, which can achieve efficient NIR-II photo-response. The multifunctional nanoparticles (Tf-IRLy NPs) were further fabricated to cross the blood-brain barrier (BBB) introducing transferrin (Tf) as a targeting ligand. Tf-IRLy NPs showed high biosafety and good tumor enrichment for GBM in vitro and in vivo, and thus enabled accurate, efficient, and less invasive NIR-II multimodal imaging and photothermal therapy. This versatile Tf-IRLy nanosystem can provide a reference for the efficient, precise and low-invasive multi-synergistic brain targeted photo-theranostics. In addition, the "extended conjugation & molecular rotor" strategy can be used to guide the design of other photothermal agents.

Chitosan/NH2-MIL-125 (Ti) scaffold loaded with doxorubicin for postoperative bone tumor clearance and osteogenesis: An in vitro study.

Surgical resection remains the primary treatment modality for bone tumors. However, it is prone to local bone defects and tumor recurrence. Therefore, there is an urgent need for multifunctional biomaterials that combine tumor treatment and bone repair after bone tumor surgery. Herein, a chitosan composite scaffold (CS/DOX@Ti-MOF) was designed for both tumor therapy and bone repair. Among them, the amino-functionalized Ti-based metal-organic framework (NH2-MIL-125 (Ti), Ti-MOF) has a high specific surface area of 1116 m2/g and excellent biocompatibility, and promotes osteogenic differentiation. The doxorubicin (DOX) loading capacity of Ti-MOF was 322 ± 21 mg/g, and DOX@Ti-MOF has perfect antitumor activity. Furthermore, the incorporation of DOX@Ti-MOF improved the physical and mechanical properties of the composite scaffolds, making the scaffold surface rough and favorable for cells to attach. CS/DOX@Ti-MOF retains the unique properties of each component. It responds to the release of DOX in the tumor microenvironment to remove residual tumor cells, followed by providing a site for cell attachment, proliferation, and differentiation. This promotes bone repair and achieves the sequential treatment of postoperative bone tumors. Overall, CS/DOX@Ti-MOF may be a promising substitute for postoperative bone tumor clearance and bone defect repair. It also provides a possible strategy for postoperative bone tumor treatment.

Amino-Functionalized Zirconium-Based Metal-Organic Frameworks as Bifunctional Nanomaterials to Treat Bone Tumors and Promote Osteogenesis.

Bone tumor patients often encounter challenges associated with cancer cell residues and bone defects postoperation. To address this, there is an urgent need to develop a material that can enable tumor treatment and promote bone repair. Metal-organic frameworks (MOFs) have attracted the interest of many researchers due to their special porous structure, which has great potential in regenerative medicine and drug delivery. However, few studies explore MOFs with dual antitumor and bone regeneration properties. In this study, we investigated amino-functionalized zirconium-based MOF nanoparticles (UiO-66-NH2 NPs) as bifunctional nanomaterials for bone tumor treatment and osteogenesis promotion. UiO-66-NH2 NPs loading with doxorubicin (DOX) (DOX@UiO-66-NH2 NPs) showed good antitumor efficacy both in vitro and in vivo. Additionally, DOX@UiO-66-NH2 NPs significantly reduced lung injury compared to free DOX in vivo. Interestingly, the internalized UiO-66-NH2 NPs notably promoted the osteogenic differentiation of preosteoblasts. RNA-sequencing data revealed that PI3K-Akt signaling pathways or MAPK signaling pathways might be involved in this enhanced osteogenesis. Overall, UiO-66-NH2 NPs exhibit dual functionality in tumor treatment and bone repair, making them highly promising as a bifunctional material with broad application prospects.

Multifunctional CuFe2O4@HA as a GSH-depleting nanoplatform for targeted photothermal/enhanced-chemodynamic synergistic therapy.

Chemodynamic therapy (CDT), which converts overexpressed hydrogen peroxide (H2O2) in tumor cells to hydroxyl radicals (•OH) by Fenton reactions, is considered a prospective strategy in anticancer therapy. However, the high level of glutathione (GSH) and poor Fenton catalytic efficiency contribute to the suboptimal efficiency of CDT. Herein, we present a multifunctional nanoplatform (CuFe2O4@HA) that can induce GSH depletion and combine with photothermal therapy (PTT) to enhance antitumor efficacy. CuFe2O4@HA nanoparticles could release Cu2+ and Fe3+ after entering tumor cells by targeting hyaluronic acid (HA). Subsequently, Cu2+ and Fe3+ were reduced to Cu+ and Fe2+ by GSH, where Cu+/Fe2+ significantly catalyzed H2O2 to produce a higher level of •OH, and the depletion of GSH disrupted the antioxidant capacity of the tumor. Therefore, depleting GSH substantially enhances the level of •OH in tumor cells. In addition, CuFe2O4@HA nanoparticles have considerable absorption in the near-infrared (NIR) region, which can stimulate excellent PTT effects. More importantly, the heat generated by PTT can further enhance the Fenton catalysis efficiency. In vitro and in vivo experiments have demonstrated the excellent tumor-killing effect of CuFe2O4@HA nanoparticles. This strategy overcomes the problem of insufficient CDT efficacy caused by GSH overexpression and poor catalytic efficiency. Moreover, this versatile nanoplatform provides a reference for self-enhanced CDT and PTT/CDT synergistic targeted therapy.

Inhibiting Osteolytic Breast Cancer Bone Metastasis by Bone-Targeted Nanoagent via Remodeling the Bone Tumor Microenvironment Combined with NIR-II Photothermal Therapy.

Bone is one of the prone metastatic sites of patients with advanced breast cancer. The "vicious cycle" between osteoclasts and breast cancer cells plays an essential role in osteolytic bone metastasis from breast cancer. In order to inhibit bone metastasis from breast cancer, NIR-II photoresponsive bone-targeting nanosystems (CuP@PPy-ZOL NPs) are designed and synthesized. CuP@PPy-ZOL NPs can trigger the photothermal-enhanced Fenton response and photodynamic effect to enhance the photothermal treatment (PTT) effect and thus achieve synergistic anti-tumor effect. Meanwhile, they exhibit a photothermal enhanced ability to inhibit osteoclast differentiation and promote osteoblast differentiation, which reshaped the bone microenvironment. CuP@PPy-ZOL NPs effectively inhibited the proliferation of tumor cells and bone resorption in the in vitro 3D bone metastases model of breast cancer. In a mouse model of breast cancer bone metastasis, CuP@PPy-ZOL NPs combined with PTT with NIR-II significantly inhibited the tumor growth of breast cancer bone metastases and osteolysis while promoting bone repair to achieve the reversal of osteolytic breast cancer bone metastases. Furthermore, the potential biological mechanisms of synergistic treatment are identified by conditioned culture experiments and mRNA transcriptome analysis. The design of this nanosystem provides a promising strategy for treating osteolytic bone metastases.

Aggregation-Induced emission photosensitizer with lysosomal response for photodynamic therapy against cancer.

Photosensitizers play a key role in bioimaging and photodynamic therapy (PDT) of cancer. However, conventional photosensitizers usually do not achieve the desired efficacy in PDT due to their poor photostability, targeting ability, and responsiveness. Herein, we designed a series of photosensitizers with aggregation-induced emission (AIE) effect using benzothiazole- triphenylamine (BZT-triphenylamine) as the parent nucleus. The synthesized compound SIN ((E)-2-(4-(diphenylamino)styryl)-3-(4-iodobutyl)benzo[d]thiazol-3-ium) exhibits good biocompatibility, photostability, and bright emission in the near-infrared range (600-800 nm). The fluorescence emission intensity is responsive to viscosity, with significant fluorescence enhancement (48 times) and high fluorescence quantum yield (4.45 %) at high viscosity. Moreover, SIN has particular lysosome targeting properties with a Pearson correlation coefficient (PCC) of 0.97 and has good 1O2 generation ability under white light irradiation, especially in a weak acidic environment. Thus, SIN can realize good bioimaging ability and photodynamic therapeutic efficacy under the highly viscous and weakly acidic environment of lysosomes in the tumor cells. This study indicates that SIN has potential as a multifunctional organic photosensitizer for bioimaging and PDT of tumor.

All-in-one CoFe2O4@Tf nanoagent with GSH depletion and tumor-targeted ability for mutually enhanced chemodynamic/photothermal synergistic therapy.

In the complex and severe tumor microenvironment, the antitumor efficiency of nanomedicines is significantly limited by their low-efficacy monotherapy, non-tumor targeting, and systemic toxicity. Herein, to achieve tumor-targeted and enhanced chemodynamic/photothermal therapy (CDT/PTT), we fabricated an "all-in-one" biocompatible transferrin-loaded cobalt ferrate nanoparticle (CoFe2O4@Tf (CFOT)) with multiple functions by a simple solvothermal method and the following transferrin (Tf) functionalization. Upon exposure to 808 nm laser irradiation, CFOT, as a novel photothermal agent, exhibited outstanding phototherapeutic activity because of its excellent photothermal conversion efficiency (η = 46.5%) for high-performance PTT. Moreover, CFOT with multiple redox pairs could efficiently convert endogenous H2O2 to hazardous hydroxyl radicals (˙OH) via Fenton reactions while scavenging overexpressed GSH in the tumor microenvironment to realize self-reinforcing CDT. Importantly, CFOT undergoes a promoted Fenton-type reaction upon increasing the temperature under a photothermal effect and could augment PTT by high-level ˙OH, exhibiting a considerably enhanced synergistic therapeutic effect. In vitro and in vivo experimental results demonstrated that CFOT has good potential as an "all-in-one" nanoagent to combine photothermal, chemodynamic, and tumor targeting for efficient tumor elimination.

Bifunctional scaffolds for tumor therapy and bone regeneration: Synergistic effect and interplay between therapeutic agents and scaffold materials.

Bone tumor patients often face the problems with cancer cell residues and bone defects after the operation. Therefore, researchers have developed many bifunctional scaffolds with both tumor treatment and bone repair functions. Therapeutic agents are usually combined with bioactive scaffolds to achieve the "bifunctional". However, the synergistic effect of bifunctional scaffolds on tumor therapy and bone repair, as well as the interplay between therapeutic agents and scaffold materials in bifunctional scaffolds, have not been emphasized and discussed. This review proposes a promising design scheme for bifunctional scaffolds: the synergistic effect and interplay between the therapeutic agents and scaffold materials. This review summarizes the latest research progress in bifunctional scaffolds for therapeutic applications and regeneration. In particular, it summarizes the role of tumor therapeutic agents in bone regeneration and the role of scaffold materials in tumor treatment. Finally, a perspective on the future development of bifunctional scaffolds for tumor therapy and bone regeneration is discussed.

A Facile and Universal Method for Preparing Polyethylene Glycol-Metal Hybrid Nanoparticles and Their Application in Tumor Theranostics.

Metal ions are of widespread interest owing to their brilliant biomedical functions. However, a simple and universal nanoplatform designed for assembling a range of functional metal ions has not been explored. In this study, a concept of polyethylene glycol (PEG)-mediated transport of metal ions is proposed. 31 types of PEG-metal hybrid nanoparticles (P-MNPs) are successfully synthesized through anionic ring-opening polymerization (ROP), "thiol-ene" click reaction, and subsequent incorporation with multiple metal ions. Compared with other methods, the facile method proposed in this study can provide a feasible approach to design MNPs (mostly <200 nm) containing different metal ions and thus to explore their potential for cancer theranostics. As a proof-of-concept demonstration, four types P-MNPs, i.e., PEG-metal hybrid copper nanoparticles (PEG-Cu NPs), ruthenium nanoparticles (PEG-Ru NPs), and manganese nanoparticles (PEG-Mn NPs) or gadolinium nanoparticles (PEG-Gd NPs), are proven to be tailored for chemodynamic therapy, photothermal therapy, and magnetic resonance imaging of tumors, respectively. Overall, this study provides several metal ions-based nanomaterials with versatile functions for broad applications in cancer theranostics. Furthermore, it offers a promising tool that can be utilized for processing other metal-based nanoparticles and exploring their potential in the biomedical field.

A mitochondria-targeted thiazoleorange-based photothermal agent for enhanced photothermal therapy for tumors.

Organic small molecules with near-infrared (NIR) absorption hold great promise as the phototheranostic agents for clinical translation by virtue of their inherent merits such as well-defined chemical structure, high purity and good reproducibility. Probes that happen to be based on cyanine dyes exhibit strong NIR-absorbing and efficient photothermal conversion, representing a new class of photothermal agents (PAs) for photothermal therapy (PTT), and taking into account the heat susceptibility of Mitochondria (Mito), we designed and prepared a mitochondria-targeted organic small molecule (Mito-BWQ) based on thiazole orange maternal unit that can effectively kill tumor cells through the hyperpyrexia generated in the lesions under exogenous laser irradiation. The Confocal laser scanning microscope was employed to determine the preferential targeting of Mito-BWQ to the mitochondria of MCF-7 cells and U87 cells. When subjected to 600 nm laser radiation, Mito-BWQ produced an increase in temperature in test systems and this increase was dependent on both the laser power and probe concentration. In vitro tests, cytotoxicity was observed when cells were incubated with Mito-BWQ and exposed to laser irradiation. The PTT in vivo also showed that Mito-BWQ performed remarkably in tumor inhibition. This study thus provides a vital starting point for the creation of thiazole orange-based PTT formulations and promotes further advances in the field of PAs-based anticancer research and therapy.

Effect of Conjugation Length on Photoinduced Charge Transfer in π-Conjugated Oligomer-Acceptor Dyads.

A series of π-conjugated oligomer-acceptor dyads were synthesized that feature oligo(phenylene ethynylene) (OPE) conjugated backbones end-capped with a naphthalene diimide (NDI) acceptor. The OPE segments vary in length from 4 to 8 phenylene ethynene units (PEn-NDI, where n = 4, 6 and 8). Fluorescence and transient absorption spectroscopy reveals that intramolecular OPE → NDI charge transfer dominates the deactivation of excited states of the PEn-NDI oligomers. Both charge separation (CS) and charge recombination (CR) are strongly exothermic (ΔG0CS ∼ -1.1 and ΔG0CR ∼ -2.0 eV), and the driving forces do not vary much across the series because the oxidation and reduction potentials and singlet energies of the OPEs do not vary much with their length. Bimolecular photoinduced charge transfer between model OPEs that do not contain the NDI acceptors with methyl viologen was studied, and the results reveal that the absorption of the cation radical state (OPE+•) remains approximately constant (λ ∼ 575 nm) regardless of oligomer length. This finding suggests that the cation radical (polaron) of the OPE is relatively localized, effectively occupying a confined segment of n ≤ 4 repeat units in the longer oligomers. Photoinduced intramolecular electron transfer dynamics in the PEn-NDI series was investigated by UV-visible femtosecond transient absorption spectroscopy with visible and mid-infrared probes. Charge separation occurs on the 1-10 ps time scale with the rates decreasing slightly with increased oligomer length (ßCS ∼ 0.15 Å-1). The rate for charge-recombination decreases in the sequence PE4-NDI > PE6-NDI ∼ PE8-NDI. The discontinuous distance dependence in the rate for charge recombination may be related to the spatial localization of the positive polaron state in the longer oligomers.

Intercalation of Alkynylplatinum(II) Terpyridine Complexes into a Helical Poly(phenylene ethynylene) Sulfonate: Application to Protein Sensing.

The interactions of two anionic poly(phenylene ethynylene) sulfonate-conjugated polyelectrolytes (mPPESO3- and pPPESO3-) with two alkynylplatinum(II) terpyridine complexes (Pt2+ and Pt3+) were studied. The Pt(II) complexes interact with helical mPPESO3- by intercalation within the polymer helix to form a "guest-host" ensemble. Titration of Pt(II) complexes into an aqueous solution of mPPESO3- gives rise to efficient quenching of the polymer's fluorescence; meanwhile, triplet metal-metal-to-ligand charge transfer (3MMLCT) state emission from the intercalated Pt(II) complexes appears when the ensembles are excited into the polymer's absorption band. The 3MMLCT state emission implies that the Pt(II) complexes aggregate or dimerize on the mPPESO3- scaffold. The responses of the mPPESO3- and Pt(II) complex ensembles to various proteins were examined by monitoring the mPPESO3- fluorescence change. Negatively charged proteins recover the mPPESO3- fluorescence more than the positively charged proteins under physiological pH, indicating that electrostatics play an important role in the protein-ensemble interaction.

Corrugated Organic Light Emitting Diodes Using Low Tg Electron Transporting Materials.

A corrugated organic light emitting diode (OLED) with enhanced light extraction is realized by incorporating a corrugated composite electron transport layer (ETL) consisting of two ETLs with different glass transition temperatures. The morphology of the corrugated structure is characterized with atomic force microscopy. The results show that the corrugation can be controlled by the layer thicknesses and annealing temperature. Compared with the control planar device, the corrugated OLED shows a more than 35% enhancement in current efficiency from 31 cd/A to 43 cd/A and a 20% enhancement in external quantum efficiency from 10% to 12% at 100 cd/m(2). In addition, the corrugated OLED also has a greatly improved operational stability. The LT90 lifetime of a device operated at 1000 cd/m(2) is improved greater than 100-fold in the corrugated OLED.

Conjugated Polyelectrolyte-Sensitized TiO2 Solar Cells: Effects of Chain Length and Aggregation on Efficiency.

Two sets of conjugated polyelectrolytes with different molecular weights (Mn) in each set were synthesized. All polymers feature the same conjugated backbone with alternating (1,4-phenylene) and (2,5-thienylene ethynylene) repeating units, but different linkages between the backbone and side chains, namely, oxy-methylene (-O-CH2-) (P1-O-n, where n = 7, 9, and 14) and methylene (-CH2-) (P2-C-n, n = 7, 12, and 18). They all bear carboxylic acid moieties as side chains, which bind strongly to titanium dioxide (TiO2) nanoparticles. The two sets of polymers were used as light-harvesting materials in dye-sensitized solar cells. Despite the difference in molecular weight, polymers within each set have very similar light absorption properties. Interestingly, under the same working conditions, the overall cell efficiency of the P1-O-n series increases with a decreasing molecular weight while the efficiency of the P2-C-n series remains constant regardless of the molecular weight. Steady state photophysical measurements and dynamic light scattering investigation prove that P1-O-n polymers aggregate in solution while P2-C-n series are in the monomeric state. In P1-O-n series, a higher-molecular weight polymer results in a larger aggregate, which reduces the amount of polymers that are adsorbed onto TiO2 films and overall cell efficiency.

Effect of isomerism and chain length on electronic structure, photophysics, and sensitizer efficiency in quadrupolar (donor)2-acceptor systems for application in dye-sensitized solar cells.

We report on quadrupolar (donor)2-acceptor sensitizers for dye-sensitized solar cells (DSSCs). The acceptor units are based on dithieno[2,3-a:3',2'-c]phenazine and dithieno[3,2-a:2',3'-c]phenazine coupled to thiophene donors. The optoelectronic and photophysical properties of two sets of isomers reveal a rigid structure for linear isomers and an efficient nonradiative decay for branched isomers. These sensitizers were integrated into DSSCs, and the quadrupolar structure is an operational design, as the IPCE reached up to 38% from 400 nm to 600 nm. The lengthening of the donor chain increases the efficiency, demonstrating the appeal of these oligomeric dyes for DSSCs.

Enhanced Fluorescence Properties of Poly(phenylene ethynylene)-Conjugated Polyelectrolytes Designed to Avoid Aggregation.

A new class of nonaggregating conjugated polyelectrolytes exhibits efficient fluorescence in aqueous solution. Analysis by optical spectroscopy and transmission electron microscopy reveals a unique structure-property correlation between oxygen substitution and aggregation.

Bifurcation analysis and effects of changing ionic conductances on pacemaker rhythm in a sinoatrial node cell model.

The electrical excitation (action potential generation) of sinoatrial node (cardiac pacemaker) cells is directly related to various ion channels (pore-forming proteins) in cell membranes. In order to analyze the relation between action potential generation and ion channels, we use the Yanagihara-Noma-Irisawa (YNI) model of sinoatrial node cells, which is described by the Hodgkin-Huxley-type equations with seven variables. In this paper, we analyze the global bifurcation structure of the YNI model by varying various conductances of ion channels, and examine the effects of these conductance changes on pacemaker rhythm (frequency of action potential generation). The coupling effect on pacemaker rhythm is also examined approximately by applying external current to the YNI model.