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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.

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.

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.

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.

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.

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.