Anti-Colon Cancer Activity of Copper-Doped Folate Carbon Dots/MnO2 Complexes Based on Oxygenation and Immune-Enhancing Effects.

In clinical practice, the treatment of colon cancer is faced with the dilemma of metastasis and recurrence, which is related to immunosuppression and hypoxia. Immune checkpoint blockade (ICB) is a negative regulatory pathway of immunity. Immune checkpoint blockade (ICB) is an important immunotherapy method. However, inadequate immunogenicity reduces the overall response rate of ICB. In this study, a tumor microenvironment-responsive nanomedicine (Cu-FACD@MnO2@FA) was prepared to increase host immune response and increase intracellular oxygen levels. Cu-FACD@MnO2@FA preferentially enriched at the tumor site, combined with the immune checkpoint inhibitor alpha PD-L1, induced sufficient immunogenicity to treat colon cancer. Immunofluorescence detection of tumor cells and tissues showed that the expression of hypoxa-inducing factor 1α was significantly down-regulated after treatment and the expression of immunoactivity-related proteins was significantly changed. In vivo treatment in a bilateral tumor mouse model showed complete ablation of the primary tumor and efficient inhibition of the distal tumor. In this study, for the first time, the oxygenation effects of MnO2-coated Cu-doped carbon dots and chemodynamic therapy and a strategy of combining with immuno-blocking therapy were used for treating colon cancer.

Enhanced catalytic activity of Fe3O4-carbon dots complex in the Fenton reaction for enhanced immunotherapeutic and oxygenation effects.

Tumor metastasis and recurrence are closely related to immune escape and hypoxia. Chemodynamic therapy (CDT), photodynamic therapy (PDT), and photothermal therapy (PTT) can induce immunogenic cell death (ICD), and their combination with immune checkpoint agents is a promising therapeutic strategy. Iron based nanomaterials have received more and more attention, but their low Fenton reaction efficiency has hindered their clinical application. In this study, Fe3O4-carbon dots complex (Fe3O4-CDs) was synthesized, which was modified with ferrocenedicarboxylic acid by amide bond, and crosslinked into Fe3O4-CDs@Fc nano complex. The CDs catalyzed the Fenton reaction activity of Fe3O4 by helping to improve the electron transfer efficiency, extended the reaction pH condition to 7.4. The Fe3O4-CDs@Fc exhibit exceptional optical activity, achieving a thermal conversion efficiency of 56.43 % under 808 nm light and a photosensitive single-line state oxygen quantum yield of 33 % under 660 nm light. Fe3O4-CDs@Fc improved intracellular oxygen level and inhibited hypoxia-inducing factor (HIF-1α) by in-situ oxygen production based on Fenton reaction. The multimodal combination of Fe3O4-CDs@Fc (CDT/PDT/PTT) strongly induced immune cell death (ICD). The expression of immune-related protein and HIF-1α was investigated by immunofluorescence method. In vivo, Fe3O4-CDs@Fc combined with immune checkpoint blocker (antibody PD-L1, αPD-L1) effectively ablated primary tumors and inhibited distal tumor growth. Fe3O4-CDs@Fc is a promising immune-antitumor drug.

Immunogenic Cell Death Induction and Oxygenation by Multifunctional Hollow Silica/Copper-Doped Carbon Dots.

The metastasis and recurrence of cancer are related to immunosuppression and hypoxia in the tumor microenvironment. Activating immune activity and improving the hypoxic environment face essential challenges. This paper reports on a multifunctional nanomaterial, HSCCMBC, that induces immunogenic cell death through powerful photodynamic therapy/chemodynamic therapy synergistic antitumor effects. The tumor microenvironment changed from the immunosuppressive type to immune type, activated the immune activity of the system, decomposed hydrogen peroxide to generate oxygen based on Fenton-like reaction, and effectively increased the level of intracellular O2 with the assistance of 3-bromopyruvate, a cell respiratory inhibitor. The structure and composition of HSCCMBC were characterized by transmission electron microscopy, X-ray photoelectron spectroscopy, X-ray diffraction, infrared spectroscopy, etc. Oxygen probe RDPP was used to investigate the oxygen level inside and outside the cell, and hydroxyl radical probe tetramethylbenzidine was used to investigate the Fenton-like reaction ability. The immunofluorescence method investigated the expression of various immune markers and hypoxia-inducing factors in vitro and in vivo after treatment. In vitro and in vivo experiments indicate that HSCCMBC is an excellent antitumor agent and is expected to be a candidate drug for antitumor immunotherapy.

Immunoantitumor Activity and Oxygenation Effect Based on Iron-Copper-Doped Folic Acid Carbon Dots.

Cancer metastasis and recurrence are closely associated with immunosuppression and a hypoxic tumor microenvironment. Chemodynamic therapy (CDT) and photothermodynamic therapy (PTT) have been shown to induce immunogenic cell death (ICD), effectively inhibiting cancer metastasis and recurrence when combined with immune adjuvants. However, the limited efficacy of Fenton's reaction and suboptimal photothermal effect present significant challenges for successfully inducing ICD through CDT and PTT. This paper described the synthesis and immunoantitumor activity of the novel iron-copper-doped folic acid carbon dots (CFCFB). Copper-doped folic acid carbon dots (Cu-FACDs) were initially synthesized via a hydrothermal method, using folic acid and copper gluconate as precursors. Subsequently, the nanoparticles CFCFB were obtained through cross-linking and self-assembly of Cu-FACDs with ferrocene dicarboxylic acid (FeDA) and 3-bromopyruvic acid (3BP). The catalytic effect of carbon dots in CFCFB enhanced the activity of the Fenton reaction, thereby promoting CDT-induced ICD and increasing the intracellular oxygen concentration. Additionally, 3BP inhibited cellular respiration, further amplifying the oxygen concentration. The photothermal conversion efficiency of CFCFB reached 55.8%, which significantly enhanced its antitumor efficacy through photothermal therapy. Immunofluorescence assay revealed that treatment with CFCFB led to an increased expression of ICD markers, including calreticulin (CRT) and ATP, as well as extracellular release of HMGB-1, indicating the induction of ICD by CFCFB. Moreover, the observed downregulation of ARG1 expression indicates a transition in the tumor microenvironment from an immunosuppressive state to an antitumor state following treatment with CFCFB. The upregulation of IL-2 and CD8 expression facilitated the differentiation of effector T cells, resulting in an augmented population of CD8+ T cells, thereby indicating the activation of systemic immune response.

pH-Responsive Hyaluronic Acid Nanomicelles for Photodynamic /Chemodynamic Synergistic Therapy Trigger Immunogenicity and Oxygenation.

Cancer metastasis and invasion are closely related to tumor cell immunosuppression and intracellular hypoxia. Activation of immunogenicity and intracellular oxygenation are effective strategies for cancer treatment. In this study, multifunctional nanomicelle hyaluronic acid and cinnamaldehyde is self-assembled into nanomicelles (HPCNPs) were constructed for immunotherapy and tumor cell oxygenation. The Schiff base was constructed of HPCNPs with pyropheophorbide a-Cu (PPa-Cu). HPCNPs are concentrated in tumor sites under the guidance of CD44 proteins, and under the stimulation of tumor environment (weakly acidic), the Schiff base is destroyed to release free PPa. HPCNPs with photodynamic therapeutic functions and chemokinetic therapeutic functions produce a large number of reactive oxygen species (1O2 and •OH) under exogenous (laser) and endogenous (H2O2) stimulations, causing cell damage, and then inducing immunogenic cell death (ICD). ICD markers (CRT and ATP) and immunoactivity markers (IL-2 and CD8) were characterized by immunofluorescence. Downregulation of Arg1 protein proved that the tumor microenvironment changed from immunosuppressive type (M2) to antitumor type (M1). The oxidation of glutathione by HPCNP cascades to amplify the concentration of reactive oxygen species. In situ oxygenation by HPCNPs based on a Fenton-like reaction improves the intracellular oxygen level. In vitro and in vivo experiments demonstrated that HPCNPs combined with an immune checkpoint blocker (α-PD-L1) effectively ablated primary tumors, effectively inhibited the growth of distal tumors, and increased the oxygen level in tumor cells.

A General Synthesis of Nanostructured Conductive Metal-Organic Frameworks from Insulating MOF Precursors for Supercapacitors and Chemiresistive Sensors.

Two-dimensional conjugated metal-organic frameworks (2D c-MOFs) are emerging as a unique subclass of layer-stacked crystalline coordination polymers that simultaneously possess porous and conductive properties, and have broad application potential in energy and electronic devices. However, to make the best use of the intrinsic electronic properties and structural features of 2D c-MOFs, the controlled synthesis of hierarchically nanostructured 2D c-MOFs with high crystallinity and customized morphologies is essential, which remains a great challenge. Herein, we present a template strategy to synthesize a library of 2D c-MOFs with controlled morphologies and dimensions via insulating MOFs-to-c-MOFs transformations. The resultant hierarchically nanostructured 2D c-MOFs feature intrinsic electrical conductivity and higher surface areas than the reported bulk-type 2D c-MOFs, which are beneficial for improved access to active sites and enhanced mass transport. As proof-of-concept applications, the hierarchically nanostructured 2D c-MOFs exhibit a superior performance for electrical properties related applications (hollow Cu-BHT nanocubes-based supercapacitor and Cu-HHB nanoflowers-based chemiresistive gas sensor), achieving over 225 % and 250 % improvement in specific capacity and response intensity over the corresponding bulk type c-MOFs, respectively.

Multifunctional Tumor-Targeting Carbon Dots for Tumor Microenvironment Activated Ferroptosis and Immunotherapy in Cancer Treatment.

As an emerging cancer treatment strategy, ferroptosis is distinguished by the perturbation of lipid metabolism equilibrium and the accumulation of lipid peroxidation. However, the efficacy is consistently hindered by excessive GSH in the tumor microenvironment (TME). Here, this work designed and prepared multifunctional tumor-targeting carbon dots (FG-CDs@Cu) for ferroptosis and immunotherapy. Cu2+ in FG-CDs@Cu rapidly depletes high concentrations of GSH and inhibits glutathione peroxidase 4 (GPX4) expression in an acidic TME. Meanwhile, the generated Cu+ produced reactive oxygen species (ROS) through Fenton-like reaction. Due to the high efficiency of ROS production and GSH depletion, ferroptosis mediated by oxidative stress is significantly enhanced by FG-CDs@Cu in vivo, which can induce immunogenic cell death and promote CD8+ T cell infiltration. Meanwhile, the generated O2 effectively improves the hypoxic environment of the cells and leads to the reduction of hypoxia factor-1α (HIF-1α) expression, which activates the transformation of tumor-promoting M2-type tumor-associated macrophages (TAMs) to tumor-inhibiting M1-type TAMs, further enhancing the immune response and ferroptosis. The in vivo tests suggested that FG-CDs@Cu could efficiently suppress tumor growth in the mouse model and did not cause obvious toxicity. The combination with antiprogrammed death-ligand 1 (αPD-L1) synergy immune therapy could effectively restrain the growth of distal tumors, suggesting the significant potential of FG-CDs@Cu in augmenting ferroptosis and immunotherapy for efficacious cancer treatment.

Small-molecular cyclic peptide exerts viability suppression effects on HepG2 cells via triggering p53 apoptotic pathways.

Cyclic peptides have become an attractive modality for drug development due to their high specificity, metabolic stability and higher cell permeability. In an effort to explore novel antitumor compounds based on natural cyclopeptide from the phakellistatin family, we found an isoindolinone-containing analog (S-PK6) of phakellistatin 6 capable of suppressing the viability and proliferation of HepG2 cells. The aim of the present study is to shed light on the mechanism of action of this novel compound. We have detected differences in gene expression before and after treatment with S-PK6 in human hepatocellular carcinoma HepG2 cell line by transcriptome sequencing. To further investigate biological effects, we have also extensively investigated the tumor cell cycle, mitochondrial membrane potential, and intracellular Ca2+ concentration after S-PK6 treatment. Based on the finding that the apoptosis was associated with the p53 signaling pathway and MAPK signaling pathway, western blotting tests were used to assess the expression level of p53 protein and its degenerative regulator MDM2 protein, which showed that S-PK6 could increase p53 levels efficiently. In summary, our results demonstrate the mechanism of action of a small-molecule cyclopeptide, which could be very useful for examining of the possible mechanisms of natural cyclopeptides.

Cu2+-Pyropheophorbide a-Cystine Conjugate: Synergistic Photodynamic/Chemodynamic Therapy and Glutathione Depletion Improves the Antitumor Efficacy and Downregulates the Hypoxia-Inducing Factor.

Cancer immune escape, metastasis, recurrence, and multidrug resistance are all associated with hypoxia in the tumor microenvironment (TME). We synthesized a CuPPaCC conjugate for reactive oxygen species (ROS)-mediated cancer therapy. CuPPaCC continuously produced cytotoxic ROS and oxygen through a photo-chemocycloreaction, alleviated hypoxia, and inhibited the expression of a hypoxia-inducing factor (HIF-1α). CuPPaCC was synthesized from pyromania phyllophyllic acid a (PPa), cystine (CC), and copper ions, and its structure was characterized by nuclear magnetic resonance (NMR) and mass spectrometry (MS). The ability of CuPPaCC to produce ROS and oxygen after photodynamic therapy (PDT) in vitro and in vivo was investigated. The ability of CuPPaCC to consume glutathione was investigated. CuPPaCC toxicity (light and dark) in CT26 cells was analyzed by MTT and live/dead cell staining. The anticancer effect of CuPPaCC in vivo was investigated in CT26 Balb/c mice. When stimulated by the TME, CuPPaCC released Cu2+ and PPaCC, and the singlet oxygen yield increased from 34 to 56.5%. The dual ROS-generating mechanism via a Fenton-like reaction/photoreaction and dual glutathione depletion via Cu2+/CC multiplied the antitumor efficacy of CuPPaCC. The photo-chemocycloreaction continued to produce oxygen and maintained high ROS levels even after PDT, significantly alleviating hypoxia in the TME and downregulating the expression of HIF-1α. CuPPaCC thus showed excellent antitumor activity in vitro and in vivo. These results showed that the strategy could be effective in improving the antitumor efficacy of CuPPaCC and could be used as a synergistic regimen for cancer therapy.

Cu2+-pyropheophorbide-a-cystine conjugate-mediated multifunctional mesoporous silica nanoparticles for photo-chemodynamic therapy/GSH depletion combined with immunotherapy cancer.

Photodynamic therapy (PDT) and chemodynamic therapy (CDT) can activate immunogenicity, so PDT and CDT combined immunotherapy is a promising treatment strategy. However, insufficient hydrogen peroxide activity, hypoxia, and overexpressed glutathione in the tumor microenvironment (TME) significantly impaired the ability to activate immunogenicity. Thus, in this paper, self-reinforcing conjugates Cu2+-Pyropheophorbide-a-Cysteine (CuPPaCC), combined synergetic NIR and pH triggered PDT/CDT with glutathione depletion ability was constructed. CuPPaCC was encapsulated in mesoporous silica, and spherical HSCuPPaCC nanoparticles were prepared by Hyaluronic acid (HA) on the silica surface by Schiff base modification. HSCuPPaCC has tumor-specific targeting via HA mediated. In acidic solution, the Schiff base of HSCuPPaCC is destroyed and CuPPaCC is released (>70%), with excellent pH response release function. The results of the MTT analysis showed that the PDT/CDT synergistic anti-tumor effect was significant. HSCuPPaCC was activated in TME, catalyzing the decomposition of hydrogen peroxide to generate hydroxyl radicals and oxygen, alleviating TME hypoxia, replenishing oxygen to PDT, and significantly down regulating hypoxia factor HIF-1α expression. HSCuPPaCC has an excellent dual ROS mechanism and a dual depleting GSH mechanism resulting in a surge in intracellular ROS levels to efficiently kill cancer cells, enhance the ability to induce immunogenicity, and make tumors more sensitive to checkpoint PD-L1 blockade therapy. With the CT26 mouse model, not only the primary tumor was eradicated, but also the distal tumor at the end of treatment was completely suppressed by HSCuPPaCC combined with anti-PD-L1 immune checkpoint blockade therapy.

A carbon dot-doped Cu-MOF-based smart nanoplatform for enhanced immune checkpoint blockade therapy and synergistic multimodal cancer therapy.

Immune checkpoint blockade (ICB) is a kind of promising anti-tumor immunotherapy that can block the negative immune regulatory pathways using a particular antibody. Weak immunogenicity in most patients is a key obstacle to ICB therapy. Photodynamic therapy (PDT) is a non-invasive treatment that can enhance the immunogenicity of the host and realize systemic anti-tumor immunotherapy; yet tumor microenvironment hypoxia and glutathione overexpression severely restrict the PDT effect. To overcome the above issues, we design a combination therapy based on PDT and ICB. We prepared red carbon dot (RCD)-doped Cu-metal-organic framework nanoparticles (Cu-MOF@RCD) as smart nano-reactors because their tumor microenvironment and near-infrared light responsive property can decompose tumor endogenous H2O2 through Fenton-like reactions. Cu-MOF@RCD also shows clear near-infrared photothermal therapy (PTT) effect and has an ability to deplete glutathione (DG), which together enhances decomposition of cellular H2O2 and amplifies reactive oxygen species (ROS) levels in cells, thus leading to enhanced PDT and chemodynamic therapy (CDT) effect. Moreover, programmed cell death-ligand 1 antibody (anti-PD-L1) is used together to enable combination therapy, as Cu-MOF@RCD can significantly enhance host immunogenicity. In summary, the combination of Cu-MOF@RCD with anti-PD-L1 antibody exerts a synergistic PDT/PTT/CDT/DG/ICB therapy and can be used to eradicate the primary tumors and inhibit the growth of untreated distant tumors and tumor metastasis.

Organic disulfide-modified folate carbon dots for tumor-targeted synergistic chemodynamic/photodynamic therapy.

Carbon dots (CDs) have great potential for cancer diagnosis and treatment. Photodynamic therapy and chemodynamic therapy are promising treatments mediated by reactive oxygen species (ROS), which have the advantages of being minimally invasive, having no multi-drug resistance, and having no systemic toxic side effects. However, the tumor microenvironment (TME) and poor targetability often reduce the therapeutic effect. In this work, we have successfully prepared folate-based carbon dots (FCP-CDs) from folic acid (FA), citric acid (CA), and polyethyleneimine (PEI) for tumor-targeting. The surface of FCP-CDs was modified using organic disulfide, 3,3'-dithiodipropionic acid (DTPA), and a photosensitizer (PS) pyropheophorbide-a (PPa) to form a tumor microenvironment-responsive nanoplatform, FCP-CDs@DTPA@PPa (named FCPPD), for synergistic cancer therapy. The results showed that FCPPD effectively preserved the tumor target specificity of folic acid and the photodynamic therapeutic (PDT) activity of PPa, and could provide additional chemodynamic therapeutic (CDT) function by reacting with hydrogen peroxide (H2O2) to generate ˙OH. The introduction of DTPA, which contains disulfide bonds, endows FCPPD with an excellent ability to deplete glutathione (GSH) in tumors via intracellular redox reactions, amplifying intracellular oxidative strain and enhancing ROS-based therapeutic effects. Systematic in vitro and in vivo studies under various conditions have shown that the obtained FCPPD nanoparticles have good biocompatibility and could be a promising therapeutic agent for imaging-guided PDT/CDT combination therapy.

Cyclopeptide-based Anti-liver Cancer Agents: A Mini-review.

Chemotherapy is one of the most important treatment modalities for liver cancer, especially for those who are judged as being unsuitable for surgical resection, local ablative therapy, or transarterial chemoembolization. However, the efficacy of chemotherapy is still unsatisfactory due to the long duration, side effects and the tendency to develop drug resistance. The development of novel anti-liver cancer drugs remains imperative. Cyclopeptides have been recognized as new chemical modalities in drug design due to their unique constrained structures, extensive biological activities, higher metabolic stability, cell permeability and bioavailability than linear peptides. A lot of cyclic peptides have been found with potential anti-proliferative activity against malignant cells, and many of them showed excellent anti-liver cancer activity. In this review, we will discuss in detail the structures and the anti-liver cancer activity of small and medium-sized cyclopeptides, aiming to offer some elicitation to chemotherapeutic drug design based on cyclopeptides.

Tricholosterols A-D, four new ergosterol derivatives from the mushroom Tricholoma terreum.

Four ergosterol derivatives, named tricholosterols A-D (1-4), have been isolated from the fruiting bodies of Tricholoma terreum. Their chemical structures have been determined using a combination of spectroscopic analysis as well as computational methods. Compound 1 possesses a rare D-ring opening ergosterol skeleton, while compounds 2-4 are rare degraded ergosterols. Compounds 1 and 4 exhibited moderate inhibitory activity against NO production with IC50 values of 27.6 and 31.8 µM, respectively. This is the first report of steroids from T. terreum.

Copper nanocrystalline-doped folic acid-based super carbon dots for an enhanced antitumor effect in response to tumor microenvironment stimuli.

Chemodynamic therapy (CDT) is a promising cancer treatment strategy to induce tumor cell apoptosis with harmful reactive oxygen species (ROS), yet over-expression of glutathione (GSH) in the tumor microenvironment (TME) severely depletes the ROS and limits the CDT efficacy. Copper-containing materials could efficiently decrease the level of GSH in the TME. In this study, copper nanocrystalline-doped folic acid-based super carbon dots (FA-CDs@Cux) were prepared to realize an enhanced antitumor effect in response to tumor microenvironment stimuli. Folic acid (FA) was used as a source of carbon dots to improve the targetability of nanomaterials to tumor cells with over-expressed FA receptors. Copper existed mainly in the form of copper nanocrystals, which were embedded on the carbon core by in situ reduction of Cu2+ by gluconic acid. The prepared composites were found to reduce the intracellular H2O2 into hydroxyl radicals (˙OH) and consume GSH efficiently in tumor cells. Copper-doping enabled the CDs to absorb near-infrared light and to give a high photothermal transformation efficiency (54.3%) and high singlet oxygen atom yield (56.83%), endowing the super carbon dots with synergetic CDT/PTT/PDT functions in response to the TME and NIR stimuli, which have been investigated systematically by in vitro and in vivo biological experiments.

Pyropheophorbide-a/(001) TiO2 Nanocomposites with Enhanced Charge Separation and O2 Adsorption for High-Efficiency Visible-Light Degradation of Ametryn.

It is highly desired to enhance charge separation and O2 adsorption of the pyropheophorbide-a (Ppa) to promote visible-light activity and stability. Herein, Ppa modified 001-facet-exposed TiO2 nanosheets (Ppa/001T) nanocomposites with different weight ratios were fabricated via the self-assembly approach by OH induced. Compared with the bare Ppa, the 8% amount optimized 8Ppa/001T sample displayed 41-fold enhanced activity for degradation of Ametryn (AME) under visible-light irradiation. The promoted photoactivities could be attributed to the accelerated charge carrier's separation by coupling TiO2 as thermodynamic platform for accepting the photoelectrons with high energy from Ppa and the promoted O2 adsorption because of the residual fluoride on TiO2. As for this, a distinctive two radicals (•O2- and •OH) involved pathway of AME degradation is carried out, which is different from the radical pathway dominated by •O2- for the bare Ppa. This work is of utmost importance since it gives us detailed information regarding the charge carrier's separation and the impact of the radical pathway that will pave a new approach toward the design of high activity visible-light driven photocatalysts.

Self-Supply Oxygen ROS Reactor via Fenton-like Reaction and Modulating Glutathione for Amplified Cancer Therapy Effect.

Reactive oxygen species (ROS) are highly reactive oxidant molecules that can kill cancer cells through irreversible damage to biomacromolecules. ROS-mediated cancer therapies, such as chemodynamic (CDT) and photodynamic therapy (PDT), are often limited by the hypoxia tumor microenvironment (TME) with high glutathione (GSH) level. This paper reported the preparation, characterization, in vitro and in vivo antitumor bioactivity of a meso-tetra(4-carboxyphenyl)porphine (TCPP)-based therapeutic nanoplatform (CMMFTP) to overcome the limitations of TME. Using Cu2+ as the central ion and TCPP as the ligand, the 2D metal-organic framework Cu-TCPP was synthesized by the solvothermal method, then CMMFTP was prepared by modifying MnO2, folic acid (FA), triphenylphosphine (TPP), and poly (allylamine hydrochloride) (PAH) on the surface of Cu-TCPP MOFs. CMMFTP was designed as a self-oxygenating ROS nanoreactor based on the PDT process of TCPP MOFs and the CDT process by Cu(II) and MnO2 components (mainly through Fenton-like reaction). The in vitro assay suggested CMMFTP caused a 96% lethality rate against Hela cells (MTT analysis) in specific response to TME stimulation. Moreover, the Cu(II) and MnO2 in CMMFTP efficiently depleted the glutathione (80%) in tumor cells and consequently amplified ROS levels to improve CDT/PDT effects. The FA-induced tumor targeting and TPP-induced mitochondria targeting further enhanced the antitumor activity. Therefore, the nanoreactor based on dual targeting and self-oxygenation-enhanced ROS mechanism provided a new strategy for cancer therapy.

Novel Isoindolinone-Based Analogs of the Natural Cyclic Peptide Fenestin A: Synthesis and Antitumor Activity.

Small- and medium-sized cyclopeptides have been found to have extensive bioactivities and have drawn much attention from medicinal chemists. In the work described in this paper, various cyclic peptide analogs of Fenestin A were synthesized by intramolecular photoinduced electron-transfer cyclization reactions to study the influence of slight structural changes on the bioactivity of small cyclopeptides. The incorporation of thiazole and rigid isoindolinone fragments was found to improve the bioactivity of the cyclopeptide. Detailed in vitro studies of the apoptosis mechanism, mitochondrial membrane potential, cell cycle, intracellular Ca2+ concentration, and lactate dehydrogenase activity following treatment with a cyclopeptide showed that the cyclopeptide could induce apoptosis of tumor cells and lead to cycle arrest in the G2/M phase. The research also suggested that the photoinduced reaction could be applied to construct cyclic peptides stereoselectively, and the introduction of rigid fragments could enhance the biological activity of cyclopeptide drugs.

Photoinduced Synthesis of Methylated Marine Cyclopeptide Galaxamide Analogs with Isoindolinone as Anticancer Agents.

The methylation of amino acid residues has played an important role in the biological function of bioactive peptides. In this paper, various methyl-modified and stereostructural-modified marine cyclopeptide galaxamide analogs with isoindolinone were synthesized by a photoinduced single electron transfer cyclization reaction. It was found that the single-methyl substitution was beneficial for the bioactivity of cyclic analogs with isoindolinone fragments, and the influence of methylation on bioactivity is uncertain and is sometimes case-specific. The compound with a single methyl group at Gly5 (compound 8) showed the strongest antiproliferative activity against HepG-2 cells. The tumor cell apoptosis, cell cycle, mitochondrial membrane potential, intracellular Ca2+ concentration and lactate dehydrogenase activity have been studied extensively to evaluate the antitumor potential of compound 8. Western blotting tests showed that compound 8 could decrease the MDM2 level and increase p53 levels efficiently. Careful molecular docking suggested that cyclic peptide 8 could bind firmly with MDM2 oncoprotein, indicating that MDM2 may be a potential drug target of the prepared peptides.

Cascading Photoelectric Detecting and Chemiresistive Gas-Sensing Properties of Pb5 S2 I6 Nanowire Mesh for Multi-Factor Accurate Fire Alarm.

Accurate fire warning is very important for people's life and property safety. The most commonly used fire alarm is based on the detection of a single factor of gases, smoke particles, or temperature, which easily causes false alarm due to complex environmental conditions. A facile multi-factor route for fabricating an accurate analog fire alarm using a Pb5 S2 I6 nanowire mesh based on its photoelectric and gas-sensing dual function is presented. The Pb5 S2 I6 nanowire mesh presents excellent photoelectric detection capabilities and is sensitive to ppm-level NO2 at room temperature. Under the "two-step verification" circuit of light and gas factors, the bimodal simulation fire alarm based on this Pb5 S2 I6 nanowire mesh can resist the interference of complex environmental factors and effectively reduce the false alarm rate.