“NIR-triggered ROS storage”photodynamic intraocular implant for high-efficient and safe posterior capsular opacification prevention

Posterior capsular opacification(PCO)is the leading cause of vision loss after cataract,mainly caused by the adhesion,proliferation and trans-differentiation of post-operative residual lens epithelial cells(LECs).Effective PCO prevention remains a huge challenge to ophthalmologists and researches for decades.Herein,we developed a“NIR-triggered ROS storage”intraocular implant(CTR-Py-Pp IX)based on capsular tension ring(CTR),which is concurrently linked with photosensitizer protophorphyrin IX(Pp IX)and energy storage2-pyridone derivative(Py),to guarantee instantaneous and sustainable ROS generation for LECs killing,aiming to achieve more efficient and safer photodynamic therapy(PDT)to effectively prevent PCO.The silylated Pp IX-Si and Py-Si were covalently conjugated to the plasma activated CTR surface to obtain CTR-Py-Pp IX.Results demonstrated that CTR-Py-Pp IX had dual functions of PDT and battery,in which Pp IX could generate ROS extracellularly under irradiation,with one part directly inhibiting LECs by lipid peroxidation(LPO)induction of cell membranes.Meanwhile,the excess ROS stored in Py could be continuously released to amplify LPO levels after the irradiation was removed.Ultimately,the proliferation of LECs in capsular bag was completely inhibited under mild irradiation conditions,achieving a sustainable and controlled PDT effect for effective PCO prevention with good biocompatibility.This NIR-triggered ROS storage intraocular implant would provide a more efficient and safer approach for long-term PCO prevention.

Screening of Different <i>Artemisia</i>spp. from Western Ghats of Maharashtra for an Anti-Malarial Compound—Artemisinin

Artemisinin, an endoperoxide sesquiterpene lactone has proven effective in treating drug resistant cases of malaria and cancer. Artemisia annua [sweet wormwood] is the sole source for artemisinin production in many countries. To counter the low content in leaves and costly chemical synthesis process in India, alternative ways to produce artemisinin have been sought. In current study, we collected A. pallens, A. japonica and A. nilagirica from Western Ghats of Maharashtra, India and analyzed artemisinin content. Samples were extracted from leaves and florets in various extraction conditions and analyzed using different chromatographic techniques. Thin layer chromatography (TLC) and high performance thin layer chromatography (HPTLC) analysis showed the presence of compound with endoperoxide linkage in A. nilagirica. High performance liquid chromatography (HPLC) analysis showed the detection of artemisinin in methylene dichloride florets extract of A. japonica, but the concentration was too low [1.3 mg/g dry wt.] for further analyses. Gas chromatography/mass spectrometry (GC/MS) analysis identified structurally important components in the A. nilagirica ethyl acetate extract which explores the biosynthetic pathway of artemisinin from its most important precursor amorpha-4,11-diene. This is the first report of chromatographic screening of these Indian varieties of Artemisia spp. for artemisinin content.

EPR Study of the Thermal Decomposition of Transannular Peroxide of Anthracene

Thermal decomposition of transannular peroxide of anthracene (POA) (or 9,10-epidioxido anthracene) was studied by means of electron paramagnetic resonance spectroscopy (EPR) in the solid as well as in the liquid phases. Decomposition process proceeds via cleavage of the O-O bridge of the POA molecule, generating thus an alcoxy intermediate radical. Its concentration increases to a certain equilibrium stage during the time scale of the experiment. EPR spectra in the solid state were of the singlet type at the temperatures over 350 K, a doublet like anisotropic spectra were measured at the room temperature, both having g-value 2.0033. EPR spectrum from POA decomposed in benzene indicates four protons with higher (2aH = 0.305 mT, 2aH = 0.335 mT) and four protons with a lower (2aH = 0.075 mT, 2aH = 0.105 mT) splitting constants, corresponding well the radical expected after cleavage of O-O bridge.

Reversibly sensitizing-storing-releasing ^(1)O_(2) within a single platinum(Ⅱ)-acetylide-based metallacycle molecule via laser power modulation

Tumor hypoxia severely limits the therapeutic efficacy of photodynamic therapy(PDT) for solid tumors,which is highly dependent on tissue oxygen concentration.In this study,we developed a platinum(Ⅱ)-acetylide-based metallacycle compound bearing six 1,4-dimethylnaphthalenes(DMN) groups,and controlled the photodynamic and photothermal effects of the compound by adjusting the power of 730 nm laser to achieve reversible sensitization,storage and release of 1~O_(2) within a single molecule.The compound formed nanoparticles by self-assembly and exhibited good water solubility and biocompatibility.Under laser irradiation,the strong spin-orbit coupling of platinum atoms in the metallacycle facilitated 1~O_(2) generation.The produced 1~O_(2) was captured by the DMN carriers and transported into the hypoxic tumor,where 1~O_(2) release was triggered owing to the good photothermal effect of the extended conjugation of the metallacycle.During therapy,the metallacycle serving as a photosensitizer,1~O_(2) carrier,and photothermal reagent,achieved the synergistic therapy of PDT/PTT,demonstrating the versatility of the metallacycle.This study proposes a new strategy to develop phototherapy agents that are suitable for hypoxic tumors.

A Singlet Oxygen Reservoir Based on Poly-Pyridone and Porphyrin Nanoscale Metal-Organic Framework for Cancer Therapy

Here,a methacrylate-modified pyridone derivative(mPYR)was loaded into a porphyrin nanoscale metal-organic framework(porphyrin-nMOF).Then,the loaded mPYR was further polymerized to obtain poly-pyridone(poly-mPYR)to form poly-mPYR loaded porphyrin-nMOF,which is designated as PLP and used as a reservoir of singlet oxygen(^(1)O_(2)).It was found that PLP could quickly capture^(1)O_(2)in vitro and slowly release^(1)O_(2)in vivo to induce cancer cell death.The release of^(1)O_(2)was light and oxygen independent,and the entire process did not cause intracellular oxygen consumption.PLP also displayed good therapeutic effect in the treatment of both solid tumor and lung metastasis cancer.This strategy of oxygenand light-independent^(1)O_(2)treatment presents great potential for treating refractory cancer.Also,the form of^(1)O_(2)capturing polymer-loaded nMOF expands the biomedical applications of MOFs and polymers,which can be used as a platform for biomedical applications.

Artemisinin as a Chinese Medicine,Selectively Induces Apoptosis in Pancreatic Tumor Cell Line

Objective： To investigate the possible mechanism through which Artemisinin induced apoptosis in pancreatic cell line. Methods： Column chromatography, thin layer chromatography （TLC） and proton NMR spectroscopy were used to purify Artemisinin. The flowcytometry was employed to detect apoptosis and reactive oxygen species （ROS）. Results： The results indicated that 50% inhibiting concentration （ICso value） for pancreatic cell line （RIN） was 45 μmol/L of Artemisinin. Artemisinin had no cytotoxic effect on the growth of peripheral blood lymphocytes. The mechanism of apoptosis was evaluated by measuring intraceliular ROS. It was shown that Artemisinin-induced apoptosis occurred independently of the binding of CD95L to CD95 receptor in the RIN cells. Moreover, Artemisinin, in a dose-dependent manner, could significantly increase the level of ROS. Conclusion： Artemisinin can induce apoptosis in the RIN cells via the generation of ROS and triggering the intrinsic pathway of cell death.

Synthesis of N^(11)-anchoring biotinylated artemisinin derivatives and their preliminary biological assessment

Unique endoperoxide moiety of artemisinin and its derivatives has been considered the functionality exhibiting highly potent antimalarial and anticancer activities.To investigate the mechanisms of their biological actions,development of suitable molecular probes including biotinylated derivatives is of extreme significance.The synthesis and preliminary biological assessment of four new biotinylated artemisinin derivatives have been reported in this work.

A Diterpene Endoperoxide from Microtoena insuavis （Hance） Prain ex Dunn

A novel endoperoxlde diterpene, 7a-hydroxy-abieta-8（14）-en-18-oi 9α,13α-endoperoxide （compound 1）, was isolated from the stems of Microtoena insuavis （Hance） Prain ex Dunn, along with 4,4＇-dlhydroxytruxillic acid （compound 2）, gallic acid （compound 3）, ellaglc acid （compound 4）, 3-O-methylellaglc acid 3＇-O-α- rhamnopyranoslde （compound 5）, 3＂＇-O-methylcrenatoslde （compound 6）, crenatoslde （compound 7）, aptgenin （compound 8）, succinic acid （compound 9）, β-sitosterot （compound 10）, and β-daucosterol （compound 11）. The structures of these compounds were elucidated on the basis of spectral evidence.