A Review of Light Sources and Enhanced Targeting for Photodynamic Therapy.

Photodynamic Therapy (PDT), as a clinically approved modality for the treatment of various disordered diseases including cancer, has received great advances in recent years. By preferentially accumulating non-toxic Photosensitizers (PSs) in the pathological area, and in situ generation of cytotoxic reactive oxygen species (ROS) under local irradiation by a light source with appropriate wavelength, PDT works in a dual-selective manner. Over the past decades, numerous studies and reviews on PDT mainly focused on activable PSs and the newly emerging PSs in PDT. However, to the best of our knowledge, there are few articles on the systematic introduction of light sources and limited reports about targeted strategies in PDT. This review comprehensively summarizes various light sources applied in PDT together with typical enhanced targeting strategies, and outlines their advantages and disadvantages, respectively. The clinical applications and future perspectives in light sources are also partly presented and discussed.

Development of new self-assembled cationic amino liposomes for efficient gene delivery.

A library of 83 structurally diverse cationic amino liposomes is rationally designed and parallelly synthesized for the transfection of plasmid DNA and siRNA. Our designed self-assembled liposomes not only exhibit excellent transfection efficiency in HEK 293T cells and mouse embryonic stem cells, but also show low cytotoxicity.

Cell-based high-throughput screening of cationic polymers for efficient DNA and siRNA delivery.

Development of non-viral gene vectors which can efficiently and safely transfect plasmid DNA and siRNA into cells is of great importance for gene therapy. Despite lots of efforts spent, it is still imperative to develop suitable gene vectors with better transfection efficiency and low cytotoxicity. To this end, we successfully designed, synthesized and screened a library of 120 polymers (via nucleophilic substitution reaction between dihalides and amines). With cell-based transfection screening assays, 120 polymers were tested to evaluate their transfection efficiency of transporting DNA and siRNA into cells. Our results indicated that hydrophobic modification could greatly enhance cationic polymers' transfection efficiency, and polymers with long linkers usually showed better transfection performance, especially for polymers with the linker of 1, 12-dibromododecane (L3 linker). Besides, polyalkylamines exhibited better transfection efficiency with the polymer particle size around 200 nm and the zeta potential in the range of + 40 mV to +50 mV. Interestingly, polymer particles made from N15HL3 not only exhibited better DNA transfection efficiency in HEK 293T cells but also showed higher siRNA transfection efficiency in U87 Luc-GFP cells together with low cell toxicity than Lipofectamine 2000 (one of commercial transfection reagents). Therefore, it is hoped that our study here not only provides promising gene vector candidates for further evaluation in gene therapy, but also provides valuable insights for better understanding of the relationship between the chemical structures and gene transfection efficiency to rationally design better non-viral gene vectors for gene therapy in the future.

Pyridine-Embedded Phenothiazinium Dyes as Lysosome-Targeted Photosensitizers for Highly Efficient Photodynamic Antitumor Therapy.

Development of new photosensitizers (PSs) with high photodynamic efficacy and minimal side effects is of great interest in photodynamic therapy (PDT). In this work, we reported several pyridine-embedded phenothiazinium (pyridophenothiazinium) dyes, which could be conveniently synthesized in a few short steps and acted as highly efficient and potent PSs to selectively localize to lysosomes and photosensitively kill cancer cells. Among them, compound 5, which possessed the ability of promoting intracellular reactive oxygen species (ROS) upon light irradiation by almost 40-fold higher than that of methylene blue (MB, a general phenothiazinium-based PS), exhibited a remarkable phototherapeutic index (PI = 53.8) against HT29 cancer cells, leading to eradication of large solid tumors (∼300 mm3) in a xenograft mouse model without apparent side effects. These results suggest that the pyridophenothiazinium dyes developed herein, especially compound 5, may serve as promising lysosome-targeted PSs for efficient photodynamic antitumor therapy.

Recent advance on PTP1B inhibitors and their biomedical applications.

Protein Tyrosine Phosphatase 1B (PTP1B), as one of the most important members in PTP superfamily, plays a vital role in conducting various cellular functions. So far, PTP1B has been reported to be involved in the development of many diseases including obesity, diabetes, cancers and cardiovascular diseases. Development of potent and specific PTP1B inhibitors and studies on the structure-activity relationship (SAR) between their chemical structures and their biological activity have drawn increasing attention as they could not only modulate the PTP1B functions inside the cells but also provide useful lead compounds for the treatment of various PTP1B-associated diseases. To this end, we herein summarized the recent developments of PTP1B inhibitors, and different kinds of high-throughput screening strategies for the identification of potential PTP1B inhibitors as well as their potential biomedical applications, and we also provided some perspectives in the concluding remarks in this work.

[Purification and functional analysis of Helicobacter pylori UreB protein fragment].

OBJECTIVE: To establish an effective method for purification of Helicobacter pylori UreB fragment and conduct functional analysis of the purified protein. METHODS: The protein fragment expression was induced by IPTG and the expressed protein was purified through affinity chromatography and ion-exchange chromatography. The purity of the fragment was determined by high-performance liquid chromatography (HPLC), and the specific biological activity of the purified fragment was assayed by urease activity inhibition test. RESULTS: The protein fragment was highly expressed in E. coli with a purity over 91%. The protein fragment showed highly specific biological activity and the specific antibody induced by this fragment in rabbits could inhibit the activity of urease in a dose-dependent manner. CONCLUSION: The UreB fragment with high purity and biological activity can be applied for further studies.