Crocin Ameliorates Diabetic Nephropathy through Regulating Metabolism, CYP4A11/PPARγ, and TGF-ß/Smad Pathways in Mice.

INTRODUCTION: Crocin is one of the main components of Crocus sativus L. and can alleviate oxidative stress and inflammation in diabetic nephropathy (DN). However, the specific mechanism by which crocin treats DN still needs to be further elucidated. METHOD: In the present study, a mouse model of DN was first established to investigate the therapeutic effect of crocin on DN mice. Subsequently, non-targeted metabolomics techniques were used to analyze the mechanisms of action of crocin in the treatment of DN. The effects of crocin on CYP4A11/PPARγ and TGF-ß/Smad pathway were also investigated. RESULT: Results showed that crocin exhibited significant therapeutic and anti-inflammatory, and anti-oxidative effects on DN mice. In addition, the non-targeted metabolomics results indicated that crocin treatment affected several metabolites in kidney. These metabolites were mainly associated with biotin metabolism, riboflavin metabolism, and arachidonic acid metabolism. Furthermore, crocin treatment upregulated the decreased levels of CYP4A11 and phosphorylated PPARγ, and reduced the increased levels of TGF-ß1 and phosphorylated Smad2/3 in the kidneys of DN mice. CONCLUSION: In conclusion, our study validated the considerable therapeutic, anti-inflammatory, and antioxidative impacts of crocin on DN mice. The mechanism of crocin treatment may be related to the regulation of biotin riboflavin and arachidonic acid metabolism, the activation of CYP4A11/PPARγ pathway, and the inhibition of TGF-ß/Smad pathway in the kidney.

Molecular Engineering of Near-Infrared Light-Responsive BODIPY-Based Nanoparticles with Enhanced Photothermal and Photoacoustic Efficiencies for Cancer Theranostics.

Background: Engineering a single organic-molecule-based nanoparticle integrating precise diagnosis and effective therapy is of great significance for cancer treatment and future clinical applications but remains a great challenge. The goal of this study is to explore small organic molecule-based nanoparticles with high photothermal conversion efficiency for photoacoustic imaging-guided therapy. Methods: Heptacyclic B, O-chelated BODIPY structure (namely Boca-BODIPY) with strong near-infrared (NIR) absorption was designed as a theranostic agent through simply molecular engineering, in which heavy atoms and alkyl chains were introduced to promote its application for tumor theranostics. The Boca-BODIPY molecules are further encapsulated in reduced bovine serum albumin (BSA) through self-assembly. Results: The BSA-Boca-BODIPY exhibited excellent biocompatibility, extraordinary stability and high photothermal conversion efficiency up to 58.7%. The nanoparticles could dramatically enhance photoacoustic contrast of the tumor region, and the signal-to-noise ratio was increased about 14 times at 10 h post intravenous injection in 4T1 tumor-bearing mice. In addition, the nanoassemblies can efficiently convert laser energy (808 nm, 0.75 w cm-2, 5min) into hyperthermia for tumor ablation. Under the photoacoustic imaging-guided photothermal therapy (PTT), the 4T1 cancer cells were efficiently killed, no tumor recurrence and PTT-induced toxicity is observed. Conclusions: Molecular engineering is a promising way to design organic-molecule-based nanoparticles for cancer theranostics. Other organic-molecule-based nanoparticles which show great promise for imaging-guided cancer precision therapy can be engineered through this method.

pH-sensitive loaded retinal/indocyanine green micelles as an "all-in-one" theranostic agent for multi-modal imaging in vivo guided cellular senescence-photothermal synergistic therapy.

In this study, pH-sensitive loaded retinal/indocyanine green (ICG) micelles were developed to realize novel approaches for cellular senescence-photothermal synergistic therapy to treat cancer. The micelles could enable effective multi-modal imaging in vivo guided therapy and show anticancer activity in vitro and in vivo with satisfactory biosafety.

Engineering biocompatible benzodithiophene-based polymer dots with tunable absorptions as high-efficiency theranostic agents for multiscale photoacoustic imaging-guided photothermal therapy.

To date, photoacoustic imaging (PAI) and PAI-guided photothermal therapy (PTT) have been performed for noninvasive cancer diagnosis and precise ablation of tumors. To conduct concurrent PAI and PTT, it is essential to develop theranostic agents with strong optical absorption and high photothermal transfer efficiency. In this study, we have engineered theranostic agents with tunable absorptions based on conjugated polymer dots (Pdots) with different structures via the simple precipitation method. The as-synthesized Pdots exhibit strong absorption, high biocompatibility, and superior stability. In addition, the Pdots demonstrate that they can serve as contrast agents for multiscale PAI in vitro and in vivo. More importantly, a high photothermal conversion efficiency up to 40% is reached under irradiation with LED light, resulting in effective cancer treatment with extremely low light dose. Consequently, they show the potential as imaging-guided therapeutic agents for clinical cancer treatment and various biomedical applications.

Self-Quenched Metal-Organic Particles as Dual-Mode Therapeutic Agents for Photoacoustic Imaging-Guided Second Near-Infrared Window Photochemotherapy.

The nanosized metal-organic particles (NMOPs) recently have attracted tremendous attentions in biomedical applications. However, few studies have developed metal-organic nanoparticles (NMOPs) as near-infrared (NIR) II phototherapeutic agents and as Fenton-like agents for cancer theranostics. Herein, directly using organic dye and Cu(II)-ion complexes to construct NMOPs, as dual-mode therapeutic agent for PA imaging-guided photochemotherapy in NIR II window, is reported. The NMOPs are simply an assembly of Cu(II) ion and tetrahydroxyanthraquinone (THQ) complexes [Cu(II)-THQ] n through the coordination effect, van der Waals force, and π-π interactions. After modification of polyethylene glycol (PEG-(NH2)2), the obtained Cu-THQNPs endow excellent biocompatibility and stability in physiological conditions. Because of the strong absorption at NIR II window and photoinduced electrontransfer (PET) mechanism, the Cu-THQNPs not only acted as an excellent photothermal agent with extremely high light-to-heat conversion ability (51.34%) at 1064 nm for phototherapy but also explored as the PA contrast agent for precisely tracking and guiding the therapy in vivo. Most strikingly, our Cu-THQNPs can be degraded by tumor-specific acidic-cleaving of the coordination bonds and follow by the slow release of Cu(II) into tumors, which can act as Fenton-like agents to generate •OH from H2O2 for enhancing the antitumor efficacy in vivo. With almost 100% prevention of the tumor growth for ca. 14 days and no obvious toxicity based on blood biochemical/histological analysis, this work highlights the Cu-THQNPs as an efficient NIR II therapeutic agent for precise cancer theranostics.

Highly Stable Conjugated Polymer Dots as Multifunctional Agents for Photoacoustic Imaging-Guided Photothermal Therapy.

Theranostic nanomedicines involved in photothermal therapy (PTT) have received constant attention as promising alternatives to traditional therapies in clinic. However, most photothermal agents are limited by their instability and low photothermal conversion efficiency. In this study, we report new conjugated polymer dots (Pdots) as multifunctional agents for photoacoustic (PA) imaging-guided PTT. The novel 4,8-bis[5-(2-ethylhexyl)thiophen-2-yl]-2,6-bis(trimethylstannyl)benzo[1,2-b:4,5-b']dithiophene-6,6'-dibromo-N,N'-(2-ethylhexyl)isoindigo (BDT-IID) Pdots are readily fabricated though nanoreprecipitation and can absorb strongly in the 650-700 nm region. Furthermore, the BDT-IID Pdots possess a stable nanostructure and an extremely low biotoxicity. In particular, its photothermal conversion efficiency can be up to 45%. More importantly, our in vivo results exhibit that the BDT-IID Pdots are able to offer concurrently enhanced PA contrast and sufficient photothermal effect. Consequently, the BDT-IID Pdots can be exploited as a unique theranostic nanoplatform for PA imaging-guided PTT of tumors, holding great promise for their clinical translational development.

Quantification of the chemical composition variations of tumors in photothermal therapy by photoacoustic spectroscopy: an in vitro study.

In this study, the change of tumors' chemical composition in the temperature range of 20 ~70 °C is quantified for photothermal tumor therapy by photoacoustic spectroscopy (PAS) with the wavelengths of 700~1000 nm. Based on the measured photoacoustic signals, two absorption peaks at the wavelengths of 750 nm and 950 nm are identified. It is also observed that high temperature (>55 °C) is able to induce the physical and chemical degeneration of tumors. According to the in vitro tests, a new chemical species, met-hemoglobin, which is absent in normal blood, is generated at high temperature with enhanced near-infrared absorption.

Modulation of expression of p16 and her2 in rat breast tissues of mammary hyperplasia model by external use of rupifang extract.

OBJECTIVE: To observe the effect of Rupifang Extract in external use on expression of proto-oncogenes her2 and tumor suppression genes p16 in rat breast tissues of mammary hyperplasia model. To explore the mechanisms of Rupifang Extract in external use for preventing and treating mammary hyperplasia. METHODS: Thirty virginal female Wistar rats were randomized into 5 groups, 6 in each, A: blank control group; B: model group; C: the low dose group of Rupifang; D: the middle dose group of Rupifang; and E: The high dose group of Rupifang. The mammary hyperplasia rat models were produced by injecting estradiol benzoate and progesterone and irritating by tail nipping. Drug intervention was also launched during the model formation. After 30 days, the expression of her2 and p16 in breast tissues of rats in each group were detected by the SP immunohistochemical method. RESULTS: Compared with Blank control group, the expression of her2 in breast tissues in Model group was higher, and the expression of p16 was lower (P < 0.05 or P < 0.01). After intervention with Rupifang Extract, compared with Model group, the expression of her2 in breast tissues in Rupifang groups was lower, and the expression of p16 higher (P < 0.05 or P < 0.01). CONCLUSION: The mechanisms of Rupifang Extract in external application for preventing and treating mammary hyperplasia may be reducing the expression of proto-oncogenes her2 and increasing the expression of tumor suppression genes p16.