Aggregation-Induced Generation of Reactive Oxygen Species: Mechanism and Photosensitizer Construction

Luminogens with aggregation-induced emission (AIEgens) have been widely applied in the field of photodynamic therapy. Among them, aggregation-induced emission photosensitizers (AIE–PSs) are demonstrated with high capability in fluorescence and photoacoustic bimodal imaging, as well as in fluorescence imaging-guided photodynamic therapy. They not only improve diagnosis accuracy but also provide an efficient theranostic platform to accelerate preclinical translation as well. In this short review, we divide AIE–PSs into three categories. Through the analysis of such classification and construction methods, it will be helpful for scientists to further develop various types of AIE–PSs with superior performance.     

Studies of proteasome inhibition and apoptosis induction in triple‐negative breast cancer cells by novel amino acid–polypyridine–copper complex

An innovative ternary copper(II) complex, [Cu(Cl‐PIP)(Tyr)Cl]_n, has been synthesized and characterized using infrared spectroscopy, elemental analysis and single‐crystal X‐ray diffraction analysis. X‐ray crystallography indicates that the Cu atom is five‐coordinated in a square‐pyramidal configuration. The unit forms a one‐dimensional chain along the crystallographic c‐axis. The complex was screened for cytotoxicity against a panel of eight human cancer cell lines, namely MDA‐MB‐231, CAL‐51, K562, HeLa, SGC‐7901, A549, MCF‐7 and SMMC‐7721. The best anticancer activity was obtained with triple‐negative breast cancer CAL‐51 and MDA‐MB‐231 cell lines, with IC₅₀ values in the range 0.035–0.10 μM, and this was better than using carboplatin. The complex inhibits proteasomal chymotrypsin‐like activity, and docking studies reveal its interaction with 20S proteasome. In addition, the complex causes accumulation of ubiquitinated proteins, induces apoptosis and inhibits cell proliferation, indicating its great potential as a novel therapy for triple‐negative breast cancer.     

Hydrogen‐Bonded Films for Zero‐Order Release of Leuprolide

Leuprolide has been widely used in androgen deprivation therapy for the treatment of advanced prostate cancer, but its use is still limited due to its short half‐life. Herein, hydrogen‐bonded layer‐by‐layer films are fabricated from PEGylated leuprolide (PEG‐LEU) and tannic acid (TA). Because of its dynamic nature, the film disintegrates gradually in water and releases PEG‐LEU and TA. The in vitro release profile indicated perfect zero‐order kinetics, which is explained by the unique release mechanism. When implanted subcutaneously in male rats, the films maintain a constant serum drug level. For a 60‐bilayer film, the serum drug level is maintained constant for ≈24 days. No initial burst release is observed, suggesting that the in vivo release also follows zero‐order kinetics. Initially, an increase in the level of serum testosterone is induced by the released drug, followed by testosterone suppression to a constant level below the castrate level, which could be maintained as long as a constant serum drug level is maintained. Since the new drug carriers avoid an initial burst release of the drug and maintain a constant serum drug level and hence a constant serum testosterone level below the castrate level, these carriers are highly promising for androgen deprivation therapy.     

Photodynamic Therapy of Oligoethylene Glycol‐Dendronized Reduction‐Sensitive Porphyrins

Graphene oxide (GO ) and its functionalized derivatives have attracted increasing attention in medical treatment. Herein, a reduction sensitive PEI‐GO ‐SS ‐TPP was synthesized for photodynamic therapy. More than 80% porphyrin release was observed in the presence of 10 mmol•L⁻¹ DTT in one day. The confocal laser scanning microscopy confirmed that the cell uptake efficiency of PEI‐GO‐SS‐TPP was remarkably enhanced as compared to free porphyrin which was significantly dependent on incubation time. For photodynamic therapy, GSH‐OEt could effectively increase the photodynamic therapy efficiency of PEI‐GO ‐SS ‐TPP . Compared with free porphyrin, the toxicity from PEI‐GO ‐SS ‐TPP is much higher with a low IC₅₀ (2.1 µg/mL ) value. All results indicate that the PEI‐GO ‐SS ‐TPP PSs are promising for photodynamic therapy.     

pH‐ and Thiol‐Responsive BODIPY‐Based Photosensitizers for Targeted Photodynamic Therapy

A diiodo distyryl boron dipyrromethene (BODIPY) core was conjugated to two ferrocenyl quenchers through acid‐labile ketal and/or thiol‐cleavable disulfide linkers, of which the fluorescence and photosensitizing properties were significantly quenched through a photoinduced electron‐transfer process. The two symmetrical analogues that contained either the ketal or disulfide linkers could only be activated by a single stimulus, whereas the unsymmetrical analogue was responsive to dual stimuli. Upon interaction with acid and/or dithiothreitol (DTT), these linkers were cleaved selectively. The separation of the BODIPY core and the ferrocenyl moieties restored the photoactivities of the former in phosphate buffered saline and inside the MCF‐7 breast cancer cells, rendering these compounds as potential activable photosensitizers for targeted photodynamic therapy. The dual activable analogue exhibited the greatest enhancement in intracellular fluorescence intensity in both an acidic environment (pH 5) and the presence of DTT (4 mm ). Its photocytotoxicity against MCF‐7 cells also increased by about twofold upon preincubation with 4 mm of DTT. The activation of this compound was also demonstrated in nude mice bearing a HT29 human colorectal carcinoma. A significant increase in fluorescence intensity in the tumor was observed over 9 h after intratumoral injection.     

Preliminary study on singlet oxygen production using CeF3:Tb3+@SiO2-PpIX

Luminescent properties and singlet oxygen production using CeF₃:Tb³⁺-based nanoparticles modified with SiO₂ and protoporphyrin IX (PpIX) were studied. CeF₃:Tb³⁺ nanopowder was prepared via sol–gel route, with subsequent surface coating by SiO₂ layer and the conjugation with photosensitive PpIX molecules. Radioluminescence spectra suggest an energy transfer from Ce³⁺ to Tb³⁺ ions and from Tb³⁺ to molecules of PpIX photosensitizer. The energy transfer was confirmed by photoluminescence decay curves. Singlet oxygen production was detected using a reaction of ¹O₂ with 3’-(p-aminophenyl) fluorescein (APF) chemical probe after X-Ray excitation. Qualitative changes in time resolved photoluminescence spectra in the region of 520 nm indicate ¹O₂ generation. Studied nanocomposites may be good candidates for the application in X-ray induced photodynamic therapy.     

Amine containing cationic methacrylate copolymers as efficient gene delivery vehicles to retinal epithelial cells

Non‐viral gene delivery vectors have emerged as potential alternatives in the field of gene therapy by replacing the biological viral vectors. DNA–cationic polymer complexes are one of the most promising systems to target many inborn or acquired diseases without the utilization of conventional drugs. Despite the excellent binding efficiency of cationic polymers, the gene transfection seems limited to date. In this work, a series of ammonium‐based block‐copolymers with different alkyl side chains (ethyl, butyl, and hexyl) and functionality (alcohol, amine, and alkyl) have been prepared to evaluate their capacity to deliver genetic material. First, different ionic liquid monomers with different pendent functional groups were prepared and characterized. Then, polyplexes elaborated with different polymers at several polymer DNA ratios (w/w) were characterized in terms of size, zeta potential, and DNA binding, release, and protection capacity. Finally, the transfection efficiency and cell viability was evaluated in ARPE19 cells. We found that only the systems containing the amine pendent group were able to transfect ARPE19 cell and, that this amine containing polymer was less cytotoxic even at high polymer/DNA ratios (30:1). In conclusion, our studies suggested that the proper selection of the pendent group substantially impacts overall transfection efficiency of cationic polymers. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 280–287     

Mass spectrometry imaging as a tool for surgical decision‐making

Despite significant advances in image‐guided therapy, surgeons are still too often left with uncertainty when deciding to remove tissue. This binary decision between removing and leaving tissue during surgery implies that the surgeon should be able to distinguish tumor from healthy tissue. In neurosurgery, current image‐guidance approaches such as magnetic resonance imaging (MRI) combined with neuronavigation offer a map as to where the tumor should be, but the only definitive method to characterize the tissue at stake is histopathology. Although extremely valuable information is derived from this gold standard approach, it is limited to very few samples during surgery and is not practically used for the delineation of tumor margins. The development and implementation of faster, comprehensive, and complementary approaches for tissue characterization are required to support surgical decision‐making – an incremental and iterative process with tumor removed in multiple and often minute biopsies. The development of atmospheric pressure ionization sources makes it possible to analyze tissue specimens with little to no sample preparation. Here, we highlight the value of desorption electrospray ionization as one of many available approaches for the analysis of surgical tissue. Twelve surgical samples resected from a patient during surgery were analyzed and diagnosed as glioblastoma tumor or necrotic tissue by standard histopathology, and mass spectrometry results were further correlated to histopathology for critical validation of the approach. The use of a robust statistical approach reiterated results from the qualitative detection of potential biomarkers of these tissue types. The correlation of the mass spectrometry and histopathology results to MRI brings significant insight into tumor presentation that could not only serve to guide tumor resection, but that is also worthy of more detailed studies on our understanding of tumor presentation on MRI. Copyright © 2013 John Wiley & Sons, Ltd.