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Semiconducting polymers usually with high photostability, reactive oxygen species (ROS) generation ability and photothermal conversion efficiency hold tremendous promise for phototherapy. In this study, a biodegradable tri-component semiconducting polymer (NDT) has been designed and synthesized for phototheranostics. NDT nanoparticles (NPs) obtained by nano-precipitation with an ultrahigh photothermal conversion efficiency (65.6%) could be degraded in the presence of hydrogen peroxide in the tumor microenvironment (TME). Such NPs show high phototoxicity towards human cervical cancer cells (HeLa) with laser irradiation as well as negligible dark toxicity. Furthermore, the in vivo study demonstrates that tumor growth was inhibited efficiently when mice were injected with NDT NPs, even with low power laser irradiation (0.2 W cm−2). In contrast, higher power density (0.5 W cm−2) led to complete tumor suppression. No side effects were observed towards normal tissues, which was confirmed by the H&E stained pictures of the normal tissues, including heart, liver, spleen, lung and kidney. Further, hematological, liver and renal function parameters indicate the biosafety of NDT NPs.

Developing intelligent photosensitizers (PSs) responding to the tumor microenvironment (TME) to maximize the therapeutic efficacy and minimize side effects is a major problem for tumor phototherapy. In this paper, a dimethylamino (–NMe2)-functionalized boron dipyrromethene (Bodipy) derivative, namely, (E)-3-(4-(dimethylamino)styryl)-5,5-difluoro-2,8-diiodo-1,7,9-trimethyl-10-phenyl-5H-di-pyrrolo[1,2-c:2′,1′-f][1,3,2]diazaborinin-4-ium-5-uide (BDPIN) has been designed and synthesized by a Knoevenagel condensation reaction. BDPIN has a high singlet oxygen quantum yield (1O2 QY) of 74.8% in dichloromethane, and retains high 1O2 generation ability when nanoprecipitated in water with DSPE-PEG. For the synergistic therapy (photothermal conversion efficiency ∼28.6%), BDPIN NPs show a low half maximum inhibitory concentration (IC50) of 4.4 μg mL−1 towards human cervical cancer cells (HeLa). However, the dark toxicity of BDPIN NPs is almost negligible even at high concentrations. NPs with lysosome targeting ability can be triggered by the low acidity for enhanced phototherapy. Furthermore, an in vivo study demonstrates that NPs are able to inhibit tumor proliferation with laser irradiation, while causing no damage to normal tissues, suggesting the high phototoxicity, low dark toxicity and outstanding biosafety of BDPIN NPs. Results provide an approach for synthesizing nanomedicine in pH-activated enhanced phototheranostics.

Tetrazole–carboxylate ligands are excellent building blocks to construct novel coordination architectures. 5-Aminotetrazole-1-isopropionic acid (Hatzipa) and 3,3-di(1H-tetrazol-5-yl)pentanedioic acid (H4dtzpda) were prepared. And reactions of the two ligands with CdCl2·2.5H2O afforded [Cd(atzipa)2(H2O)(EtOH)] (1) and [Cd2(H2dtzpda)2(H2O)3]·3H2O (2), respectively. Compound 1 shows a two-dimensional layer structure, whereas compound 2 is a three-dimensional network composed of Cd2+ and octa-dentate H2dtzpda2− via the tetrazole-N and the carboxylate group in a μ1,1,3-COO mode. The luminescence properties of Hatzipa, H4dtzpda and the compounds were investigated at room temperature in the solid state.

Herein, an octanuclear complex [Mn8(μ4-O)4(phpy)8(MeOH)4]·MeOH·H2O based on 5-(2-hydroxyphenyl)-3-pyrazole (HphpyH) has been successfully synthesized and characterized. The compound can self-assemb...

{La(pytza)3(H2O)2·2H2O}n derived from 5-(4-pyridyl)tetrazole-2-acetic acid (Hpytza) has been synthesized by a solvothermal reaction of Hpytza and La(NO3)3·6H2O. In this compound, neighboring La3+ i...

Improving the reactive oxygen species (ROS) generation ability is of tremendous significance in designing photosensitizers (PSs). In this paper, a heavy atom free 4,4′-bis(1,2,2-triphenylvinyl)-1,1′-biphenyl (denoted as BTPE) with aggregation induced emission (AIE) was designed and synthesized by a Suzuki coupling reaction. Then nanoprecipitation with 1,2-distearoyl-sn-glycero-3-phospho-ethanolamine-N-[methoxy(polyethyleneglycol)]-2000 (DSPE-PEG-2000) was used to prepare the NPs. Singlet oxygen sensor green (SOSG) used under irradiation suggests better 1O2 generation ability of BTPE than monomer TPE. In vitro MTT assay on human cervical carcinoma cancer cells (HeLa) demonstrates that BTPE NPs with a half maximal inhibitory concentration (IC50) of 8.4 μg mL−1 are superior to TPE NPs (17.2 μg mL−1), indicating the higher phototoxicity of BTPE NPs. Furthermore, an in vivo study suggests that BTPE NPs are capable of inhibiting tumor proliferation with irradiation but the normal organs, including heart, lungs, liver, spleen and kidneys, suffer from no side effects. Our results indicate that BTPE is able to improve the phototherapy efficacy and simultaneously retains the low toxicity and good biocompatibility, compared with TPE.

Common organic molecules usually suffer from aggregation caused quenching (ACQ), which is disadvantageous for imaging guided phototherapy. It is of tremendous significance for a photosensitizer to be well soluble and simultaneously remain highly fluorescent in aqueous solution. Heavy atom free 1,1,4,4-tetraphenylbuta-1,3-diene (denoted as TPD) with aggregation induced emission (AIE) was designed and synthesized by the Knoevenagel reaction. 1,2-Distearoyl-sn-glycero-3-phospho-ethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DSPE-PEG-2000) coated TPD nanoparticles (NPs) show high singlet oxygen generation ability with singlet oxygen sensor green (SOSG) as a probe and still remain highly fluorescent in aqueous solution. In vitro cytotoxicity assay demonstrates that these NPs have a half-maximal inhibitory concentration (IC50) as low as 8.2 μg mL−1. Meanwhile, in vivo fluorescence imaging shows that these NPs can passively target the tumor by the enhanced penetration and retention (EPR) effect within 6 h. Furthermore, in vivo phototherapy suggests that TPD NPs are able to inhibit the growth of a tumor after irradiation without side effects on the normal tissues, including heart, liver, spleen, lungs and kidneys, indicating the low dark toxicity, high phototoxicity and excellent bio-compatibility of such NPs.

Photodynamic and photothermal synergistic therapy are newly developed approaches for cancer treatment. The design and preparation of photosensitizers of high phototoxicity as well as low dark toxicity are of increasing significance in minimizing the side effects and maximizing the phototherapy efficacy of such treatments. In this study, a heavy atom-free copolymer NDNT was designed and synthesized by the Stille coupling reaction. This compound shows a high singlet oxygen quantum yield of 55.2%, guaranteeing an excellent phototherapy efficacy. The nanoparticles (NPs) of NDNT obtained by nanoprecipitation with DSPE-PEG-2000 with an average diameter of 65 nm exhibit considerably high phototoxicity towards human prostate cancer cells (Du145) because their half inhibitory concentration (IC50) is as low as 3.8 μg mL−1. Simultaneously, the dark toxicity of the NPs is almost negligible, even at a high concentration. Furthermore, an in vivo study with laser irradiation by photodynamic and photothermal synergistic therapy demonstrates that the NPs are capable of inhibiting a Du145 tumor growth, compared with the control and dark group, suggesting the low dark toxicity and high phototoxicity of such NPs. The H&E stained pictures of the normal tissues show that no obvious damage occurred, indicating the biosafety of the NDNT NPs. These results provide a strategy for designing heavy atom-free copolymers for phototherapy both in vitro and in vivo.

In this paper, a heavy atom-free co-polymer (NDTT) with high singlet oxygen quantum yield (48.2%) has been designed and prepared. This polymer can be self-assembled to form uniform nanoparticles (NPs) in water. Such NPs still retain singlet oxygen generation ability with SOSG (singlet oxygen sensor green) as a probe and high photothermal conversion efficacy (35.2%). An in vitro MTT assay indicates that these NPs have a low half inhibitory concentration (IC50) of only 5.8 μg mL−1 on human prostate cancer (Du145). Moreover, in vivo investigation suggests that the growth of tumors of nude mice can be completely suppressed upon irradiation while those of the control and no illumination groups increase at a high speed, demonstrating the high phototoxicity as well as low dark toxicity of NDTT NPs. However, the normal organs, including the liver, lungs, spleen, heart and kidneys suffer from no damage, as indicated by the H&E stained pictures. Our results show that NDTT is a potential candidate for imaging guided photothermal and photodynamic synergistic therapy of prostate cancer clinically.

Naturally available compounds with bioactivity are potential candidates for cancer treatment. In this paper, we isolated hypericin (HC) from Hypericum sinense L. and investigated its antitumor activity both in vitro and in vivo. The nanoparticles (NPs) of HC were prepared by a nanoprecipitation process with 1,2-distearoyl-sn-glycero-3-phospho-ethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG-2000). With light irradiation, HC NPs not only undergo efficient electron transfer to generate the superoxide radical (O2−˙) and the hydroxyl radical (OH˙) as well as energy transfer producing singlet oxygen (1O2) for photodynamic therapy (PDT), but also non-radiative decay to produce heat for photothermal therapy (PTT) with a photothermal conversion efficiency of 29.3%. This synergistic therapy, therefore, largely boosts the phototherapy efficacy of HC NPs on human cervical cancer cells (HeLa), guaranteeing a low half maximal inhibitory concentration (IC50) of only 5.6 μg mL−1. Furthermore, in vivo studies suggest that HC NPs are capable of inhibiting tumor proliferation after laser irradiation, and the main organs remain healthy, including the heart, kidneys, liver, lungs and spleen. Our results indicate that HC NPs derived from nature with excellent phototherapy efficacies are biocompatible candidates for type I PDT/PTT synergistic cancer therapy.

In this paper, [Cu(atza)2]·2H2O has been prepared by reactions of CuCl2·2H2O and 5-aminotetrazole-1-acetic acid (Hatza). This compound has been characterized by elemental analysis, infrared spectroscopy and single crystal X-ray diffraction. This compound shows a two dimensional layer with (4,4) grid topology where atza acts as a bidentate ligand to bridge adjacent Cu(II) centers. Furthermore, CCK-8 (Cell Vitality Test Kit) assay was used to investigate the cytotoxicity on HepG2 cells (hepatocellular carcinoma), showing that it can inhibit the growth of HepG2 cells. In addition, cell cycle and apoptosis assay were also investigated.

It is of great importance for a photosensitizer to be soluble in aqueous solutions, while simultaneously remaining highly fluorescent. Towards this goal, (2-(4-bromophenyl)ethene-1,1,2-triyl)tribenzene (denoted as TPE-Br) with aggregation induced emission (AIE) was prepared. 1,2-Distearoyl-sn-glycero-3-phospho-ethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DSPE-PEG-2000) coated TPE-Br nanoparticles (NPs) have a strong ability to generate singlet oxygen using singlet oxygen sensor green (SOSG) as a probe and still retain high fluorescence in aqueous solutions. In vitro cytotoxicity assays demonstrate that these NPs are able to kill HeLa cells effectively and the half-maximal inhibitory concentration (IC50) is as low as 12 μg mL−1. Furthermore, in vivo investigation suggests that TPE-Br NPs are able to inhibit the growth of the tumors after irradiation without adverse effects to normal organs, including the heart, liver, spleen, lung and kidney. This indicates the significantly low dark toxicity and excellent biocompatibility of such NPs.

Ru (II) compounds have potential application in photodynamic therapy (PDT). In the current study, two Ru (II) compounds based on the auxiliary ligand 2,2′-bipyridine (bipy) by changing main ligands 5-(2-pyridyl) tetrazole (Hpytz) and di(2H-tetrazol-5-yl) amine (H2datz) have been successfully synthesized and characterized, [Ru (pytz)(bipy)2][PF6] (1) and [Ru(Hdatz)(bipy)2][PF6] (2). These compounds can form nanoparticles (NPs) by nano-precipitation. And [Ru(pytz)(bipy)2][PF6] NPs with a lower half maximal inhibitory concentration (IC50) of 37 μg/mL on HeLa cells than that of [Ru(Hdatz)(bipy)2][PF6] NPs (65 μg/mL). Meanwhile, negligible dark toxicity has been also observed for these NPs even under high concentrations. The results show that [Ru(pytz)(bipy)2][PF6] (1) and [Ru(Hdatz)(bipy)2][PF6] (2) NPs can inhibit cell proliferation in vitro, and may be potential candidates for photodynamic therapy.

Semiconducting polymers have been widely used for phototheranostics due to their strong absorbance in near infrared region, high photostability, excellent photothermal conversion ability. In this paper, a heavy atom free tri-component semiconducting polymer PTVT has been designed and synthesized by a Stille coupling reaction. PTVT has a high singlet oxygen quantum yield (1O2 QY) of 42.2% in DCM remains high 1O2 generation ability for the DSPE-PEG coated PTVT nanoparticles (NPs) obtained by a nanoprecipitation approach. Owing to the PDT and PTT synergistic therapy (photothermal conversion efficiency ~52.6%), PTVT NPs show a low half maximum inhibitory concentration (IC50) of 5.9 μg/mL towards human lung cancer cells (A549) with laser irradiation. And simultaneously the dark toxicity of such NPs is almost negligible even at high concentrations. Furthermore, in vivo study demonstrates that the NPs are able to inhibit tumor proliferation with laser irradiation, compared with the control and dark group, suggesting the low dark toxicity and high phototoxicity of such NPs. The H&E stained pictures of the normal tissues indicate the biosafety of PTVT NPs in that no obvious damage of heart, liver, lung, kidney and spleen was observed. The results provide an approach to designing heavy atom free semiconducting polymers for phototheranostics.

Design and preparation of photosensitizers (PSs) play an important role in photodynamic therapy (PDT). PDT mainly relies on the production of toxic reactive oxygen species (ROS) of the PSs. Conventional fluorophores, however, often suffer from aggregation caused quenching (ACQ), which limits the potential of PSs as fluorescent imaging agents. Molecules with aggregation-induced emission (AIE) properties maintain high fluorescence and dispersity in aqueous solutions, overcoming the ACQ effect. Ruthenium (II)-based AIE compounds are highly biocompatible molecules and can be used for response cell imaging. In the current study, two novel Ru(II)-based AIE compounds with main ligands 1,3-di(2H-tetrazol-5-yl)benzene (Hphbtz) by changing auxiliary ligand 2,2′-bipyridine (bipy) and 1,10-phenanthroline (phen) have been successfully synthesized and characterized, [Ru(Hphbtz)(bipy)2][PF6] (1) and [Ru(Hphbtz)(phen)2][PF6] (2). The NPs show strong intra-cellular fluorescence and also simultaneously exhibited potent cytotoxic activity. These compounds can self-assemble to form nanoparticles (NPs) by nanoprecipitation. The compounds are found to exhibit a high AIE property with emission maxima at 353 nm and 380 nm, respectively. And the compounds have the low IC50 (half maximal inhibitory concentration) of only 15 μg/mL (1.94 μM) and 13 μg/mL (1.58 μM) on HeLa cells, respectively. Meanwhile, negligible dark toxicity has been also observed for these NPs. The results show that [Ru(Hphbtz)(bipy)2][PF6] (1) and [Ru(Hphbtz)(phen)2][PF6] (2) NPs can inhibit cell proliferation in vitro, and may be potential candidates for photodynamic therapy.

Boosting the photosensitization type I process will enhance the phototherapy efficacy because the superoxide radicals (O2− ) generated during type I process are more toxic than the singlet oxygen (1O2) in type II process. Herein, [Ru(Hdtza)(phen)2][PF6] (1) and [Ru(pytz)(phen)2][PF6] (2) (phen = 1,10-phenanthroline) based on two nitrogen-rich tetrazole ligands, di(2H-tetrazol-5-yl) amine (H2dtza) and 5-(2-pyridyl)tetrazole (Hpytz) have been developed for photodynamic therapy (PDT) against lung cancer, respectively. Nanoprecipitation was used to prepare the nanoparticles (NPs) of both compounds. [Ru(Hdtza)(phen)2][PF6] NPs mainly undergo an electron transfer process to generate O2− while [Ru(pytz)(phen)2][PF6] the direct energy transfer to produce 1O2, which is responsible for the higher phototoxicity of [Ru(Hdtza)(phen)2][PF6] NPs (IC50 ~ 4.8 μg/mL) than that of [Ru(pytz)(phen)2][PF6] NPs (IC50 ~ 13.6 μg/mL) on human lung cancer cells (A549). Furthermore, in vivo study indicates that the tumor proliferation of nude mice can be effectively inhibited with the help of laser when the mice were injected with [Ru(pytz)(phen)2][PF6] NPs. This work may provide a simple strategy to design type I photosensitizers for enhanced photodynamic therapy.

Three new Ca (II) coordination polymers derived from different tetrazole-carboxylate ligands, namely [Ca(pztzma)2(H2O)2] (1), [Ca(pytza)2(H2O)2] (2), [Ca(tzpha)(4,4′-bipy)3/2(H2O)]·2H2O (3) have been prepared and characterized, where pztzma (pztzma = 2-(5-pyrazin-2-yl-tetrazol-2-yl)-propionic anion, pytza (pytza = 2-(5-pyridin-4-yl-tetrazol-2-yl)-propionic anion), tzpha (tzpha = {5-[3,5-Bis-(2-methoxycarbonylmethyl-2H-tetrazol-5-yl)-phenyl]-tetrazol-2-yl}-acetato). Nanoparticles (NPs) of the three compounds can be prepared by PEG-5000 (Polyethylene glycol-5000) co-precipitation method. And [Ca(tzpha)(4,4′-bipy)3/2(H2O)]·2H2O (3) NPs has a relatively low IC50 (half maximal inhibitory concentration) of 42 μg/mL (5.6 μM) on HeLa cells is superior to [Ca(pytza)2(H2O)2] (2) 40 μg/mL (7.8 μM) and [Ca(pztzma)2(H2O)2] (1) NPs of 33 μg/mL (6.4 μM). The migration of HeLa cells is inhibited by NPs of the three compounds. The results show that [Ca(pztzma)2 (H2O)2] (1), [Ca(pytza)2(H2O)2] (2) and [Ca(tzpha)(4,4′-bipy)3/2(H2O)]·2H2O (3) NPs can inhibit cell proliferation and migration in vitro.

Ru(II) compounds are potential candidates for photodynamic therapy (PDT) and auxiliary ligands may have an impact on the property of the resulting coordination compounds. In the present study, two Ru(II) compounds based on 5-(2-pyrazinyl)tetrazole (Hpztz) and two classic auxiliary ligands, 2,2′-bipyridine (bipy) or 1,10-phenanthroline (phen) have been prepared and characterized, namely [Ru(pztz)(bipy) 2 ][PF 6 ] ( 1 ) and [Ru(pztz)(phen) 2 ][PF 6 ] ( 2 ). The nanoparticles (NPs) of the two compounds have been prepared by self-assembly in aqueous solution. In vitro MTT assay on HeLa cells show that [Ru(pztz)(phen) 2 ][PF 6 ] with a lower IC 50 (half-maximal inhibitory concentration) of only 7.4 μg/mL is superior to that of [Ru(pztz)(bipy) 2 ][PF 6 ] (17.8 μg/mL) under irradiation. Meanwhile, negligible dark toxicity have been also observed for the two compounds. In addition, in vivo fluorescence imaging suggests that [Ru(pztz)(phen) 2 ][PF 6 ] NPs are able to target to the tumor by enhanced permeability and retention effect (EPR). Furthermore, in vivo phototherapy on nude mice demonstrate that such NPs can effectively inhibit the growth of the tumor. After treatment for 10 cycles, an obvious decrease in the tumor volume can be observed while the normal tissues, including heart, liver, spleen, lung and kidney, suffer from no damage, indicating the high phototoxicity, low dark toxicity and excellent biocompatibility of [Ru(pztz)(phen) 2 ][PF 6 ] NPs.