Radiotherapy (RT), along with surgery and chemotherapy, is a major modality of cancer therapy. Nevertheless, insufficient deposition of radiation energy in tumors and hypoxia-associated ...radioresistance remain the greatest challenges in RT. Here, we propose porous platinum nanoparticles as a new nanomedicine platform for solving these two problems at the same time using a single agent. Because of the combined advantages of a high-Z element and oxygen generation capability, porous platinum nanoparticles can significantly increase radiation-induced DNA damage, ROS stress, and cell cycle arrest by effectively depositing X-ray radiation energy within the cancer cells. Further, porous platinum nanoparticles increase tumor oxygenation by converting endogenic H2O2 to O2, thus greatly enhancing RT with no apparent in vivo toxicity to animals. This study presents a new nanomedicine strategy based on the use of porous high-Z metal nanoparticles with oxygen generation function for the synergistic enhancement of RT in cancer treatment.
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A boronate-based fluorescent probe 1 for the selective monitoring of intracellular peroxynitrite has been developed. The probe takes advantage of the fast reaction of an arylboronate group with ...peroxynitrite, yielding a corresponding phenol that undergoes spontaneous subsequent reactions to produce a strongly fluorescent product associated with a large turn-on signal.
A gold nanorod (GNR)−photosensitizer complex was developed for noninvasive near-infrared fluorescence imaging and cancer therapy. We showed that (a) fluorescence emission and singlet oxygen ...generation by AlPcS4 were quenched after complex formation with GNRs; (b) 4-fold greater intracellular uptake and better in vitro phototoxicity were observed in GNR−AlPcS4-treated cells than in free AlPcS4-treated cells; and (c) after intravenous injection of the GNR−AlPcS4 complex, tumor sites were clearly identified on near-infrared fluorescence images as early as 1 h after injection. The tumor-to-background ratio increased over time and was 3.7 at 24 h; tumor growth reduced by 79% with photodynamic therapy (PDT) alone and by 95% with dual photothermal therapy (PTT) and PDT. This novel multifunctional nanomedicine may be useful for near-infrared fluorescence imaging and PTT/PDT in various cancers.
A colorimetric and ratiometric fluorescent probe consisting of a boron-dipyrromethene (BODIPY) dye conjugated with a 2-dicyanomethylene-3-cyano-2,5-dihydrofuran (DCDHF) group has been designed for ...the selective and sensitive detection of HOCl/OCl(-)via oxidative cleavage of an alkene linker between BODIPY and DCDHF.
A new design for fluorescence probes of esterase activity that features a carboxylate‐side pro‐fluorophore is demonstrated with boron dipyrromethene (BODIPY)‐based probes 1 a and 1 b. Because the ...design relies on the enzyme‐catalyzed hydrolysis of an ester group that is not electronically activated, these probes exhibit a stability to background hydrolysis that is far superior to classical alcohol‐side profluorophore‐based probes, large signal‐to‐noise ratios, reduced sensitivity to pH variations, and high enzymatic reactivity. The utility of probe 1 a was established with a real‐time fluorescence imaging experiment of endogenous esterase activity that does not require washing of the extracellular medium.
Stable but reactive: A new design for fluorescence probes of esterase activity that features a carboxylate‐side pro‐ fluorophore is demonstrated with boron dipyrromethene (BODIPY)‐based probes 1 a (R=Me) and 1 b (R=Bn). The utility of probe 1 a was established with a real‐time fluorescence imaging experiment of endogenous esterase activity that does not require washing of the extracellular medium.
Although multifunctional upconversion imaging probes have recently attracted considerable interest in biomedical research, there are currently few methods for stabilizing these luminescent nanoprobes ...with oligonucleotides in biological systems. Herein, a method to robustly disperse upconversion nanoprobes in physiological buffers based on rational design and synthesis of nanoconjugates comprising hairpin‐DNA‐modified gold nanoparticles is presented. This approach imparts the upconversion nanoprobes with excellent biocompatibility and circumvents the problem of particle agglomeration. By combining single‐band anti‐Stokes near‐infrared emission and the photothermal effect mediated by the coupling of gold to upconversion nanoparticles, a simple, versatile nanoparticulate system for simultaneous deep‐tissue imaging and drug molecule release in vivo is demonstrated.
Current strategies for surface functionalization often yield the resulting upconversion nanoparticles with limited biocompatibility, specificity, functionality, and dispersibility in high‐salt physiological environment. To this end, a rational design and synthesis of hairpin DNA‐functionalized upconversion/gold nanoprobes is presented featuring improved stability, which is particularly useful for deep‐tissue drug delivery.
We report on the development of photosensitizer-conjugated gold nanorods (MMP2P-GNR) in which photosensitizers were conjugated onto the surface of gold nanorods (GNR) via a protease-cleavable peptide ...linker. We hypothesized that fluorescence and phototoxicity of the conjugated photosensitizers would be suppressed in their native state, becoming activated only after cleavage by the target protease matrix metalloprotease-2 (MMP2). Quantitative analysis of the fluorescence and singlet oxygen generation (SOG) demonstrated that the MMP2P-GNR conjugate emitted fluorescence intensity corresponding to 0.4% ± 0.01% and an SOG efficiency of 0.89% ± 1.04% compared to free pyropheophorbide-a. From the in vitro cell studies using HT1080 cells that overexpress MMP2 and BT20 cells that lack MMP2, we observed that fluorescence and SOG was mediated by the presence or absence of MMP2 in these cell lines. This novel activatable photosensitizing system may be useful for protease-mediated fluorescence imaging and subsequent photodynamic therapy for various cancers.
Highlights
A fucoidan-based theranostic nanogel consisting of a fucoidan backbone, redox-responsive cleavable linker and photosensitizer enables activatable fluorescence imaging of tumor sites and an ...enhanced photodynamic therapy to induce complete death of cancer.
To use fucoidan as a polymeric backbone in the nanogel platform enables cancer targeting by P-selectin binding and enhances anti-tumor effect by inhibiting the binding of the vascular endothelial growth factor.
In this study, a fucoidan-based theranostic nanogel (CFN-gel) consisting of a fucoidan backbone, redox-responsive cleavable linker and photosensitizer is developed to achieve activatable near-infrared fluorescence imaging of tumor sites and an enhanced photodynamic therapy (PDT) to induce the complete death of cancer cells. A CFN-gel has nanomolar affinity for P-selectin, which is overexpressed on the surface of tumor neovascular endothelial cells as well as many other cancer cells. Therefore, a CFN-gel can enhance tumor accumulation through P-selectin targeting and the enhanced permeation and retention effect. Moreover, a CFN-gel is non-fluorescent and non-phototoxic upon its systemic administration due to the aggregation-induced self-quenching in its fluorescence and singlet oxygen generation. After internalization into cancer cells and tumor neovascular endothelial cells, its photoactivity is recovered in response to the intracellular redox potential, thereby enabling selective near-infrared fluorescence imaging and an enhanced PDT of tumors. Since a CFN-gel also shows nanomolar affinity for the vascular endothelial growth factor, it also provides a significant anti-tumor effect in the absence of light treatment in vivo. Our study indicates that a fucoidan-based theranostic nanogel is a new theranostic material for imaging and treating cancer with high efficacy and specificity.
Fluorescent probe 1, showing a high fluorescence turn-on signal ratio, enables the real-time imaging of endogenous alkaline phosphatase (ALP) activity in living cells, and the fast and quantitative ...analysis of enzyme activity at the single-cell level.
Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, including abemaciclib, have been approved for the treatment of hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative ...advanced, and metastatic breast cancer. Despite the high therapeutic efficacy of CDK4/6 inhibitors, they are associated with various adverse effects, including potentially fatal interstitial lung disease. Therefore, a combination of CDK4/6 inhibitors with letrozole or fulvestrant has been attempted but has demonstrated limitations in reducing adverse effects, highlighting the need to develop new combination therapies. This study proposes a combination strategy using CDK4/6 inhibitors and tricyclic antidepressants to enhance the therapeutic outcomes of these inhibitors while reducing their side effects. The therapeutic efficacies of abemaciclib and desipramine were tested in different cancer cell lines (H460, MCF7, and HCT-116). The antitumor effects of the combined abemaciclib and desipramine treatment were evaluated in a xenograft colon tumor model. In vitro cell studies have shown the synergistic anticancer effects of combination therapy in the HCT-116 cell line. The combination treatment significantly reduced tumor size compared with control or single treatment without causing apparent toxicity to normal tissues. Although additional in vivo studies are necessary, this study suggests that the combination therapy of abemaciclib and desipramine may represent a novel therapeutic approach for treating solid tumors.
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