Coffee grounds-derived carbon quantum dots as peroxidase mimetics for colorimetric and fluorometric detection of ascorbic acid.

In this study, we reported the eco-responsible synthesis of iron-doped carbon quantum dots (Fe-CQDs) from waste coffee grounds through a simple hydrothermal method. The Fe-CQDs exhibited high peroxidase-like activity, which could convert 3,3',5,5'-tetramethylbenzidine (TMB) into blue ox-TMB in the presence of H2O2. After adding ascorbic acid (AA) to above system, the blue solution faded. Based on this phenomenon, a colorimetric method for visual monitoring of H2O2 and AA was developed. Meanwhile, the fluorescence of Fe-CQDs can be quenched by the formed ox-TMB via inner filter effect (IFE), followed by the recovery upon the addition of AA. Therefore, Fe-CQDs can be acted as a fluorescent probe to detect H2O2 and AA through the "on-off-on" mode. Furthermore, the dual-recognition methods based on Fe-CQDs were used to measure AA content in beverage samples. Thus, this work would shed much light on converting waste into biomass CQDs and their potential applications in biomolecular detection.

Iron porphyrin-based porous organic polymer with high peroxidase-like activity as colorimetric sensor for glutathione and ascorbic acid assay.

A new iron porphyrin-based organic polymer (Fe-POP) was synthesized through the William ether reaction. The as-prepared Fe-POP presented high chemical stability, wide pore distribution, high iron content, and strong affinity with 3,3',5,5'-tetramethylbenzidine (TMB) and hydrogen peroxide (H2O2), which contributed to its excellent peroxidase-mimicking performance. In the presence of H2O2, Fe-POP could catalyze the transparent TMB into blue ox-TMB, which could be easily distinguished by the naked eyes. Moreover, glutathione (GSH) and ascorbic acid (AA) could convert blue ox-TMB into colorless TMB due to the inhibitory effect of GSH/AA to the catalytic oxidation of TMB. Based on this phenomenon, a rapid and sensitive colorimetric method for the assay of H2O2, GSH, and AA was developed using Fe-POP as sensor. The detection limits of H2O2, GSH, and AA  were 1.37, 0.44, and 0.33 µM, respectively. Finally, the colorimetric method based on Fe-POP was used to evaluate the GSH and AA content in real samples, which provided the guidance for GSH and AA supplements in our daily diet, suggesting the significant potential of Fe-POP in practical applications.

Nanoplatform Self-Assembly from Small Molecules of Porphyrin Derivatives for NIR-II Fluorescence Imaging Guided Photothermal-Immunotherapy.

Combinatorial photothermal and immunotherapy have demonstrated great potential to remove primary tumors, suppress metastases, and prevent tumor recurrence. However, this strategy still confronts patients with many limitations, such as complex components, sophisticated construction, and inadequate therapeutic efficacy. In this work, small molecules of porphyrin derivatives (PPor) which can self-assemble into monodispersed nanoparticles without supplement of any other ingredients or surfactants are developed. The formed PPor nanoparticles (PPor NPs) exhibit highly photothermal conversion efficiency of 70% and NIR-II luminous abilities originate from the strong intramolecular charge transfer (ICT) effect of D-A structure under 808 nm laser irradiation, thus achieving NIR-II fluorescence imaging guided photothermal therapy (PTT) against primary tumors with a high cure rate. More importantly, tumor-associated antigens (TAAs), together with damage-associated molecular patterns (DAMPs) released from PTT-treated cancer cells, are proved to elicit immune responses to some degree. After combination with programmed cell death-1 (PD-1) antibodies, a robust systematic antitumor immunity is generated to restrain both primary and abscopal tumors growth, prolong survival, and prevent pulmonary metastasis on an aggressive 4T1 murine breast tumor model. Thus, this study provides a promising therapeutic paradigm with porphyrin derivatives nano-assembly as phototheranostic agents for the treatment of aggressive tumors with high efficiency.

Organic Nanoparticles Based on D-A-D Small Molecule: Self-Assembly, Photophysical Properties, and Synergistic Photodynamic/Photothermal Effects.

Cancer is one of the major diseases threatening human health. Traditional cancer treatments have notable side-effects as they can damage the immune system. Recently, phototherapy, as a potential strategy for clinical cancer therapy, has received wide attention due to its minimal invasiveness and high efficiency. Herein, a small organic molecule (PTA) with a D-A-D structure was prepared via a Sonogashira coupling reaction between the electron-withdrawing dibromo-perylenediimide and electron-donating 4-ethynyl-N,N-diphenylaniline. The amphiphilic organic molecule was then transformed into nanoparticles (PTA-NPs) through the self-assembling method. Upon laser irradiation at 635 nm, PTA-NPs displayed a high photothermal conversion efficiency (PCE = 43%) together with efficient reactive oxygen species (ROS) generation. The fluorescence images also indicated the production of ROS in cancer cells with PTA-NPs. In addition, the biocompatibility and photocytotoxicity of PTA-NPs were evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and live/dead cell co-staining test. Therefore, the as-prepared organic nanomaterials were demonstrated as promising nanomaterials for cancer phototherapy in the clinic.

Self-assembled porphyrin polymer nanoparticles with NIR-II emission and highly efficient photothermal performance in cancer therapy.

The development of new organic nanoagents with extremely high photothermal conversion efficiency and good biocompatibility has gained considerable attention in the area of photothermal cancer therapy. In this work, we designed and synthesized a new porphyrin polymer (P-PPor) with donor-acceptor (D-A) structure. P-PPor displayed intense absorbance in the near-infrared (NIR) region with the maximum peak around at 850 â€‹nm. Under excitation of 808 â€‹nm, P-PPor demonstrated the significant fluorescence in the NIR-II region (λ max â€‹= â€‹1015 â€‹nm), with the fluorescence quantum yield of 2.19%. Due to the presence of hydrophilic PEG chains and hydrophobic alkyl chains in the conjugated skeleton, the amphiphilic P-PPor could self-assemble into the nanoparticles (P-PPor NPs) with good dispersibility in water and enhanced absorption in the NIR region. Moreover, P-PPor NPs exhibited quenched fluorescence because of the aggregation-caused quenching (ACQ) effect, resulting in the distinct photothermal effect. The photothermal conversion efficiency (PCE) of P-PPor NPs was measured as 66% under 808 â€‹nm laser irradiation, higher than most of PTT agents. The remarkable photothermal effect of P-PPor NPs was further demonstrated in vitro and in vivo using 4T1 tumor mode. Meanwhile, the NIR-II fluorescence imaging in vivo indicated the high distribution of P-PPor NPs in tumor site. These results suggested that P-PPor NPs could effectively damage the cancer cells in mice under 808 â€‹nm laser irradiation, and did not cause any obvious side effects after phototherapy. Thus, P-PPor NPs could be used as a potential agent in photothermal cancer therapy with high effectiveness and safety.

Triphenylamine-perylene diimide conjugate-based organic nanoparticles for photoacoustic imaging and cancer phototherapy.

Phototherapy has gained great attention in the past decade owing to the advantages of high selectivity and low toxicity. However, it's still a challenge to develop a single photosensitizer that can achieve both photothermal and photodynamic effects. Herein, we design and synthesize a new organic compound (PIT) with a typical D-A-D structure through the covalent conjugation of perylene diimides (PDI) and triphenylamine (TPA). The amphiphilic PIT could be transformed to the nanoparticles (PIT NPs) through nanoprecipitation method. PIT NPs exhibit good water dispersibility with particle size around 70 nm. Because of the efficient NIR absorption, PIT NPs display high photothermal conversion efficiency (PCE) (η = 46.1 %) and strong photoacoustic signal under irradiation of 635 nm laser. Moreover, under the same laser irradiation, significant reactive oxygen species can be induced by PIT NPs both in aqueous solution and cancer cells. The MTT assay demonstrate the good biocompatibility and outstanding photocytotoxicity of PIT NPs. Thus, the as-prepared PIT NPs could be used as excellent candidates for photoacoustic imaging and photodynamic/photothermal therapy.

Self-assembly of methylene violet-conjugated perylene diimide with photodynamic/photothermal properties for DNA photocleavage and cancer treatment.

Near-infrared (NIR) light-activated phototherapy, such as photothermal therapy (PTT) and photodynamic therapy (PDT), has gained considerable attention due to the advantages of high efficiency and minimally invasiveness. However, the development of a single component therapeutic agent with clear structure and molecular weight that achieve photodynamic/photothermal synergistic therapy is still challenging. Herein, we design and synthesize a new smart photosensitizer (PRX) by conjugation of perylene diimide (PDI) and methylene violet (RAX). The typical donor-acceptor (D-A) structure of RAX facilitates the red-shift of absorption to the near-infrared (NIR) region. The amphiphilic PRX could self-assemble into monodispersed nanoparticles (PRX NPs) with enhanced and broadened absorption. Under a single 808 nm laser irradiation, PRX NPs could generate efficient reactive oxygen species (ROS) and heat simultaneously with the photothermal conversion efficiency as high as 59%. PRX NPs displays strong interaction with DNA and can damage plasmid DNA upon light irradiation. The biocompatibility and high phototoxicity of PRX NPs against A549 cells are further confirmed through MTT assay. Therefore, the as-prepared PRX NPs could be served as a promising antitumor nanoagent through photothermal/photodynamic combination manner.

Multifunctional theranostic nanosystems enabling photothermal-chemo combination therapy of triple-stimuli-responsive drug release with magnetic resonance imaging.

Theranostic nanosystems are emerging as a promising approach for controlled drug delivery, diagnosis and multimodal therapeutics. Herein, a multifunctional theranostic nanoplatform is reported for photothermal-chemo combination therapy functioned with magnetic and thermal imaging. Hyaluronic acid (HA) coated Fe3O4@polydopamine nanoparticles equipped with redox-sensitive disulfide linkers have been subsequently deposited with an anticancer drug, doxorubicin (DOX) (termed as FPCH-DOX NPs). These nanocomposites possess an average diameter of 120 nm, a saturation magnetization of 28.5 emu g-1, DOX loading capacity of 7.13% and a transverse relaxation rate of 171.76 mM-1 s-1. The drug release could be triggered by pH, glutathione (GSH) concentration and light irradiation. Prussian blue staining and confocal microscopy demonstrate that these nanoplatforms have improved biocompatibility and cellular uptake in CD44-positive HeLa cell lines rather than in CD44-negative NIH 3T3 normal cell lines. In vitro evaluations demonstrate that the combination therapy of FPCH-DOX NPs lowers the cell viability to 16.2%, less than that of individual chemotherapy (55.3%) or PTT (52.1%). In vivo MRI indicates that the tumor accumulation of FPCH-DOX NPs provides enhanced MRI contrast, and in vivo thermal imaging verified their localized photothermal conversion effect in tumor tissues. Importantly, FPCH-DOX NPs present remarkable anti-tumor efficacy by photothermal-chemo combination therapy. H&E and Ki67 staining tests show obvious necrosis and weak cell proliferation at the region of the tumor. Thus, FPCH-DOX NPs are promising multifunctional nanoplatforms for highly effective cancer theranostics.

Self-Assembled Naphthalimide Conjugated Porphyrin Nanomaterials with D-A Structure for PDT/PTT Synergistic Therapy.

Light-activated phototherapy, including photothermal and photodynamic therapy, has become a new way for spatiotemporal control and noninvasive treatment of cancer. In this study, two new organic porphyrin molecules (NI-Por and NI-ZnPor) with donor (D)-acceptor (A) structure were designed and synthesized. The donor-acceptor pairs facilitated the intermolecular electron transfer, resulting in the enhancement of near-infrared (NIR) absorbance and nonradiative heat generation. After self-assembling, the nanoparticles were formed with the size around 60 nm. Relative to that of organic molecules, the absorption of NI-Por NPs and NI-ZnPor NPs broadened and red-shifted to the near-infrared region. Moreover, the porphyrin-containing nanoparticles can generate heat and reactive oxygen species (ROS) simultaneously induced by a single laser (635 nm). The intracellular reactive oxygen species production of NI-Por NPs and NI-ZnPor NPs was confirmed using DCFH-DA as an indicator. Furthermore, the localization of NI-Por NP and NI-ZnPor NP in HeLa cells was verified by fluorescence confocal laser microscopy. The photocytoxicity of two nanoparticles against HeLa cells was evaluated through the CCK-8 method. The IC50 of NI-Por NPs and NI-ZnPor NPs upon 635 nm laser irradiation was calculated to be 6.92 µg/mL and 5.86 µg/mL, respectively. Furthermore, the PDT/PTT synergistic effect of NPs under a 635 nm laser was verified through different treatment groups in vitro. All these results demonstrated that the as-prepared porphyrin-based nanoparticles are promising nanoagents for PDT/PTT in clinic.

A Simple Strategy to Fabricate Phthalocyanine-Encapsulated Nanodots for Magnetic Resonance Imaging and Antitumor Phototherapy.

Photothermal agents can transfer the absorbed light to heat energy, offering a noninvasive and controllable method to kill tumor cells and tissues. Here, we develop a simple and high-output strategy to prepare photothermal nanodots (MnPc-NDs) by the self-assembly and carbonization of manganese phthalocyanine. The aggregation of phthalocyanine molecules in the nanodots induces an efficient photothermal conversion. Thanks to the high thermal stability of phthalocyanine, the macrocycle is well preserved in the core of nanodots under the controlled hydrothermal temperature. Moreover, the as-prepared MnPc-NDs disperse well in aqueous solution with an average nanoscale size around 60 nm. The intense absorption in near-infrared (NIR) region, along with efficient reactive oxygen generation, high photothermal conversion efficiency (η = 59.8%), and excellent magnetic resonance contrast performances of MnPc-NDs endow them with great potential for MRI-guided cancer phototherapy. Therefore, the contribution provides a facile way to develop theranostic MnPc-NDs for precise and efficient cancer imaging and therapy.

Organic small molecular nanoparticles based on self-assembly of amphiphilic fluoroporphyrins for photodynamic and photothermal synergistic cancer therapy.

Two new porphyrin-based organic compounds (Por and ZnPor) were synthesized by introducing hydrophilic polyethylene glycol chains and pentafluorobenzene moieties onto the parent porphyrin structure. After self-assembling into nanoparticles, the absorption spectrum of (Zn)Por NPs broadened and red-shifted to some extent, relative to that of organic molecules. Meanwhile, the fluorescence of organic molecule nanoparticles was quenched significantly, which facilitated the nonradiative thermal generation for potential applications in photothermal cancer therapy. Por NPs and ZnPor NPs presented spherical structure with average diameter about 100 nm, endowing them with tumor targeting properties based on the enhanced permeability and retention (EPR) effect. Due to the heavy atom effect, ZnPor NPs presented the higher efficiency of ROS generation than that of Por NPs. In contrast, Por NPs exhibited the better photothermal effect relative to that of ZnPor NPs under irradiation of a 635-nm laser. The photothermal conversion efficiency of Por NPs was calculated to be 16.34%. The in vitro experiments suggested that Por NPs and ZnPor NPs could enter tumor cells efficiently with good biocompatibility and exhibited high photocytotoxicity with IC50 of 7.3 µg/mL and 3.0 µg/mL, respectively. Thus, the as-prepared porphyrin nanomaterials can be used as potential photosensitizers for cancer photodynamic/photothermal synergistic therapy in vivo, benefiting from their good biocompatibility, strong near-infrared absorption, and high photodynamic and photothermal effects.

Small-Molecule Porphyrin-Based Organic Nanoparticles with Remarkable Photothermal Conversion Efficiency for in Vivo Photoacoustic Imaging and Photothermal Therapy.

Near-infrared (NIR)-absorbing organic nanoparticles (ONPs) are emerging candidates for "one-for-all" theranostic nanomaterials with considerations of safety and formulation in mind. However, facile fabrication methods and improvements in the photothermal conversion efficiency (PCE) and photostability are likely needed before a clinically viable set of candidates emerges. Herein, a new organic compound, [porphyrin-diketopyrrolopyrrole (Por-DPP)] with the donor-acceptor structure was synthesized, where porphyrin was used as a donor unit while diketopyrrolopyrrole was used as an acceptor unit. Por-DPP exhibited efficient absorption extending from visible to NIR regions. After self-assembling into nanoparticles (NPs) (∼120 nm), the absorption spectrum of Por-DPP NPs broadened and red-shifted to some extent, relative to that of organic molecules. Furthermore, the architecture of NPs enhanced the acceptor-donor structure, leading to emission quenching and facilitating nonradiative thermal generation. The PCE of Por-DPP NPs was measured and calculated to be 62.5%, higher than most of ONPs. Under 808 nm laser irradiation, the Por-DPP NPs possessed a distinct photothermal therapy (PTT) effect in vitro and can damage cancer cells efficiently in vivo without significant side effects after phototherapy. Thus, the small-molecule porphyrin-based ONPs with high PCE demonstrated promising application in photoacoustic imaging-guided PTT.