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

Photo-induced synthesis, stereochemistry and antitumor activity of valine-based small cyclopeptides were studied.

The target affinity of cyclopeptides to MDM2 protein can be improved by adjusting the molecular electrostatic potential and volume.

Red carbon dot-doped Cu-MOF nanoplatform was fabricated and used in combination with immune checkpoint blockade antitumor therapy.

Chemodynamic therapy (CDT) based intracellular chemical reactions to produce highly cytotoxic reactive oxygen species has received wide attention. However, low efficiency of single CDT in weakly acidic pH and glutathione (GSH) overexpressed tumor cells has limited its clinical application. For this study were prepared two-dimensional metal-organic framework (MOF) to improve CDT efficiency based on the combined action of bimetallic CDT, consumption of overexpressed glutathione (GSH) in cells, folic acid (FA) induced tumor targeting and triphenylphosphine (TPP) induced mitochondrial targeting. With the use of Cu(II) as the central ion and tetrakis(4-carboxyphenyl)porphyrin (TCPP) as the ligand, two-dimensional Cu-MOF nanosheets were prepared, which were surface modified by manganese dioxide based on the

Nine bisulfide-bridged bicyclopeptides were synthesized firstly by intramolecular photoinduced electron transfer cyclo-reaction using l-cystine as the linker.

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@Cu

Photodynamic therapy (PDT) involving the generation of cytotoxic reactive oxygen species under light in the presence of sufficient oxygen has been widely used in diagnosing and treating cancer. However, the ubiquitous hypoxia in many solid tumors due to their abnormal proliferation and vascularization has greatly compromised the therapeutic effect. We have designed and prepared a tumor therapeutic nanoplatform for improving PDT based on defective TiO[Formula: see text] (d-TiO[Formula: see text] with the consideration that the continuous PDT would cause hypoxic tumor microenvironment (HTM) in which many hypoxia-sensitive drugs might be activated to exert the antitumor activities. The inorganic d-TiO[Formula: see text] nanoparticles (NPs) were firstly prepared and then modified by APTES to obtain the mesoporous d-TiO[Formula: see text]@SiO2NPs. The organic photosensitizer pyropheophorbide-a (PPa) and hypoxic-sensitive agent 6-aminoflavone (AF) were then adsorbed in the mesoporous SiO2, followed by further hydrophilic PEGylation to improve the biocompatibility. Defective d-TiO[Formula: see text] and the PPa could simultaneously consume oxygen after light excitation, while the resulted HTM was utilized to activate the hypoxic-sensitive agent 6-aminoflavone (AF) to trigger anti-cancer effect. The prepared d-TiO[Formula: see text]@SiO2/PPa/AF@PEG NPs were stable in normal physiological environment, and could continuously release PPa and AF under slightly acidic conditions. The in vitro experiments against cancer cells suggested that the combination of PPa and AF displayed significantly enhanced antitumor activities than that of monotherapy. Therefore, this research offered a potential application for 6-aminoflavone in PDT-induced hypoxia to improve the antitumor effects.

It is highly desired to enhance charge separation and O

Photodynamic therapy (PDT) is inflowing the mainstream of the cancer treatments, yet the shallow light penetration, thermal damage to normal cells, poor tumor targeting, and skin phototoxicity compromised the PDT efficacy. This paper designed and prepared an upconversion nanoplatform that could effectively convert 808 nm NIR light to red and green light emission, both of which could excite photosensitizers and exert the PDT curative effects. A thin layer of mesoporous silica covering core-shell nanostructure NaGdF

A cyclic analog of natural peptide Yunnanin A was synthesized via photoinduced single electron transfer reaction (SET) in the paper. The resulting compound exhibited potent bioactivity (with IC50 values 29.25 μg mL−1 against HepG-2 cell lines and 65.01 μg mL−1 against HeLa cell lines), but almost have no toxicity to normal cells (with IC50 values 203.25 μg mL−1 against L929 cell lines), which may be served as a potential antitumor drug for medical treatment. The spatial structure was examined by experimental electronic circular dichroism (ECD) and quantum chemistry calculations. Moreover, the theoretical study suggested that special intramolecular hydrogen bonds and γ, β-turn secondary structures may be possible sources affecting cyclic peptide's bioactivity.

To overcome the serious adverse reactions, multidrug resistance and non-specificity towards tumor tissues of conventional chemotherapy drugs in cancer therapy, and the low efficiency of single photodynamic therapy owing to the hypoxic environment inside tumors, we have prepared a “from one to all” multi-mode therapy integrated nanoplatform. GFCDH nanoparticles with fluorescence imaging function were prepared based on tumor-targeting folate-conjugated chitosan loaded with doxorubicin (DOX) and photosensitizer HNPa (FCDH) as the core, and cystine-functionalized graphene oxide as a vehicle. The on–off drug control was activated by stimulation of the endogenous tumor microenvironment to enhance the intracellular multi-responsive drug delivery for tumor-targeted synergistic photothermal therapy, photodynamic therapy and chemotherapy. The drug-loading capacity of DOX and HNPa in GFCDH nanoparticles was up to 5.24% and 5.58%, respectively, and the loaded drugs could be efficiently released by acid stimulation, glutathione (GSH) reduction and near-infrared light induction. In vitro, 87% of the loaded HNPa was released within 72 hours by GSH/acid stimulation, simulating the tumor microenvironment, compared with 20% at a physiological pH of 7.4. Furthermore, it was shown that irradiation with 808 nm light induced increased drug release. GFCDH nanoparticles possessed good photothermal effect and 1O2 quantum yield (ΦΔ = 42.1%) using methylene blue (ΦΔ = 49.1%) as a reference. An MTT assay showed a higher cancer cell toxicity for GFCDH treatment with 808 nm and 700 nm light irradiation compared with single wavelength light irradiation. All the results reveal the promise for applications of this smart strategy to overcome existing barriers in chemotherapy and photodynamic therapy for enhanced anticancer therapy.

Cyclic peptides have become a powerful modality in drug development. Naturally isolated cyclic peptides such as phakellistatins have been found to have broad-spectrum bioactivity. In this paper, we have prepared an analog of phakellistatin 18, and tried to compare its bioactivity with that of our reported phakellistatin 2 analog. It was found that compound 1 derived from phakellistatin 18 showed inferior inhibiting ability compared to the phakellistatin 2 analog, similar to the phenomenon observed in the natural products (phakellistatin 2 presented stronger antitumor activity than that of phakellistatin18). We have performed molecular docking of the two analogs with the MDM2 protein using AutoDock Tools, which showed that the phakellistatin 2 analog presented stronger binding through a H-bond, providing an explanation for the bioactivity difference.

Targeted delivery of photosensitizer for antitumor photodynamic therapy has received much attention recently. In this research, a multitargeting graphene oxide (GO) nanosystem (GFFP-TPPa) was fabricated based on the magnetically targeted nano-Fe

Mitochondria are extensively researched as target sites to maximize photodynamic therapy (PDT) effects because they play crucial roles in metabolism. Here, a mitochondria targeting PDT agent, tri-triphenylphosphonium substituted meso-tetra(4-carboxyphenyl)porphyrin (TCPP-TPP) is prepared for the first time. Considering that many porphyrin derivatives are quick to aggregate, thereby reducing the PDT effect, our photosensitizer (PS) was loaded on a folic acid (FA) decorated graphene oxide (GO) nanosystem, called GF@TCPP-TPP, by electrostatic and [Formula: see text]–[Formula: see text] stacking or hydrophobic cooperative interactions, to improve the transportation of photosensitizers and enhance the therapeutic effect. Herein, we have performed a detailed study of photodynamic activity of GF@TCPP-TPP nanocomposites and evaluated their potential as a photosensitizer in PDT. An MTT assay showed that GF@TCPP-TPP inhibited HeLa cells in a concentration-dependent manner under light (650 ± 10 nm, 5 mW [Formula: see text] and 10 min), and presented remarkably improved PDT efficiency (IC[Formula: see text] g [Formula: see text] mL[Formula: see text] of equivalent TCPP-TPP) over free TCPP (IC[Formula: see text] after irradiation. Furthermore, our research indicated that Type I mechanisms (the generation of hydroxyl radicals) play a predominant role in the GF@TCPP-TPP induced PDT process. This coincides with the low singlet oxygen (1O[Formula: see text] quantum yield ([Formula: see text] [Formula: see text] 33.6%) in a DMF solution. Moreover, cell morphological changes after GF@TCPP-TPP PDT further demonstrated that GF@TCPP-TPP could induce damage and apoptotic cell death efficiently. In particular, precise delivery of photosensitizers to mitochondria was proven by organelle localization.

Photodynamic therapy (PDT) is an emerging acknowledged alternative treatment for multiple cancers. However, the efficiency of PDT is lower in tumors with imperfect vascular systems under hypoxia because anticancer therapy mediated by reactive oxygen species (ROS) is highly dependent on an adequate and sustained O2 supply. In this paper, Rattle-type Fe3O4@SiO2 mesoporous spheres are prepared using colloidal carbon spheres as templates to load artemisinin (ART) and the chlorophyll photosensitizer HNPa for localized ROS-generating therapy. HNPa was firstly reported by our group previously as a highly soluble drug and an excellent tissue penetrant. ART was considered to generate ROS based on a pH-mediated Fenton-like process. Our research shows that Fe2+ can be easily released from the Fe3O4@SiO2 nanocarrier in the tumor microenvironment by weak acidic etching, and the reaction of ART with Fe2+ from Fe3O4@SiO2-ART-HNPa can continue to perform curative functions even in the hypoxic tumor environment after PDT. Moreover, it was found that NIR light irradiation can partly enhance the production of ROS for enhanced anticancer therapy. All these results show the promise of this smart strategy to conquer the existing barriers of PDT.

A gallic acid-affinity molecularly imprinted polymer (G-MIP) was first used as an adsorbent for selective identification and capture of luteolin (LTL) in herbal medicine samples. The G-MIP was prepared by using LTL as the template, gallic acid (GA) as the functional monomer, ethylene glycol dimethacrylate (EGDMA) as the crosslinking agent, and 2,2′-azobis(2-methylpropionitrie) (AIBN) as the initiator. The properties of G-MIP were characterized by FT-IR, transmission electron microscope, scanning electron microscope, dynamic light scattering, specific surface area, and X-ray photoelectron spectrum. The adsorption conditions were optimized, and the adsorption equilibrium model and adsorption kinetics model of the adsorbent were investigated under the best experimental conditions. The saturated adsorption capacity is 1.24 mg g−1, which is not only higher than the adsorption capacity of 4-carboxyphenylboronic acid-affinity MIP adsorbent but also superior to those of many reported adsorbents for enriching of LTL. The LTL was quantified by HPLC. The linear range is 0.05–100 mg L−1, the detection limit is 0.020 mg L−1. This method was successfully applied in the selective recognition of LTL in herbal medicines with recoveries of 93.9–114.2%, and the relative standards deviations (RSDs) are 0.4–5.6%. Thus, this work provides a potential possibility and practical platform for the determination of LTL in complex matrices.

Detailed structural investigation and exploration of the potential clinical indications are necessary for the drug reevaluation of newly-approved drugs. Crizotinib is a potent and selective receptor tyrosine kinases (RTK) dual inhibitor approved for treatment of non-small cell lung carcinoma (NSCLC) by FDA. In this work, a detailed structural research of Crizotinib molecule including molecular structural optimization, Mulliken population, molecular electrostatic potential, vibrational frequencies have been performed by theoretical calculations. The chiral structure was also examined by experimental and simulated electrostatic circular dichroism (ECD) spectrum at different calculation levels. Moreover, the potential clinical indications of Crizotinib are also predicted by molecular docking based on increasing case reports in curation of various cancers. The molecular docking data supported the potential interaction of Crizotinib with various therapeutic targets. In addition to the acknowledged interactions with therapeutic target for NSCLC (C-met, ALK, NTRK), some other targets such as PD-1 and POM121 for breast and prostatic cancer, respectively, were firstly observed to be able to interact with Crizotinib, which have been confirmed by the recent clinical findings. Our research provided a probable explanation of the unique therapeutic effect of Crizotinib for breast and prostatic cancer, and also guided a way for new clinical uses for old drug such as Crizotinib.

Graphene oxide (GO) has been widely recognized as a good drug delivery vector due to its special properties and biocompatibility. Herein, a promising chlorophyll-a derivative photosensitizer, purpurin-18 methyl ester (Pu18), was introduced onto the surface of GO to investigate the drug loading and release properties. Pu18 is considered to be more suitable for the treatment of deeper tissues due to its strong absorption in the near infrared region (Q(0,0) band at 699 nm). The graphene oxide loaded Pu18 nanomaterial (GO–Pu18) was obtained via simple ultrasonic agitation and presented pH-sensitive drug release behavior. Pu18 could be released more easily from the GO–Pu18 composite in a weak acid environment than that in a neutral environment, suggesting that GO–Pu18 could be applied in tumor treatment due to the weak acid environment around tumor tissues. Moreover, GO–Pu18 showed an increased singlet oxygen (1O2) quantum yield (ΦΔ = 62.60%) compared to free Pu18 (ΦΔ = 58.82%) and showed remarkable photostability in phosphate buffer saline (PBS). In vitro experiments on HepG-2 cells showed that the GO–Pu18 composite possessed excellent photocytotoxicity and negligible dark toxicity. Cell morphological changes after PDT treatment also showed that GO–Pu18 could lead to remarkable damage of cancer cells under light, during which Type I (the generation of hydroxyl radicals) and Type II (the generation of singlet oxygen) photodynamic reactions occurred simultaneously, yet the Type II reaction might play a predominant role. The research has disclosed that the new composite GO–Pu18a is a favorable prospect in the treatment of PDT.

Two novel chiral cyclic peptide analogues of galaxamide were synthesized by photoinduced single electron transfer cyclization. Their stereochemistry was studied by experimental and theoretical ECD simulations. The title compounds were found to be active against HepG-2 cell lines (IC50 = 19.52 for 1 and 26.34 μg mL−1 for 2).

The study focuses on synthesizing novel polyhedral oligomeric silsesquioxanes functionalized boronate affinity molecularly imprinted polymer (MCM-48@P-B-MIPs) material. The MCM-48@P-B-MIPs were prepared using MCM-48 as the matrix, POSS as the auxiliary monomer, 4-vinylphenylboric acid (VPBA) as the boronate affinity functional monomer, ovalbumin (OVA) as the template molecule, and dopamine (DA) as the self-polymerizing reagent. The material was used as a solid-phase extraction (SPE) adsorbent to enrich OVA selectively. The MCM-48@P-B-MIPs exhibit excellent adsorbent properties due to rich boric acid groups and a large specific surface area. The specific imprinting sites of molecularly imprinted polymers can selectively distinguish the target protein OVA from other proteins, such as horseradish peroxidase (HRP), bovine hemoglobin (BHb), and lysozyme (Lyz). The MCM-48@P-B-MIPs show effective adsorption to selectively recognize OVA with a high adsorption capacity of 222.1 mg g−1, short adsorption time of 27 min, and a suitable imprinted factor (IF) of 2.1. The adsorbent follows the pseudo-second-order adsorption kinetics and Langmuir isotherm model. Overall, the method was successfully applied to enrich the OVA selectively in egg white samples.

Photodynamic therapy (PDT) has gained much attention in tumor therapy because of its special advantages. PDT heavily depends on the oxygen, yet the tumor microenvironment (TME) is a hypoxic and acid milieu, which weakens the PDT effect. Based on the consideration that the TME deteriorated by the PDT oxygen consumption could activate the hypoxic-sensitive small-molecule drug, we designed and prepared an integrated nanocomposite including zirconium ion metal organic framework (carrier), pyropheophorbide-a (PPa, photosensitizer), and 6-amino flavone (AF, hypoxic-sensitive drug), aiming to exert a cascaded PDT-chemotherapy (CT) antitumor effect and to solve the hypoxic challenge. The prepared nanocomposite showed great stability under the physiological (pH 7.4) condition and could continuously release PPa and AF under slightly acidic pH condition (pH 6.4), suggesting a tumor microenvironment responsive feature. Systematical in vitro and in vivo researches under various conditions (light, dark, hypoxic and normoxic) have showed that the obtained Zr-MOF@PPa/AF@PEG nanoparticles (NPs) had good biocompatibility and could achieve efficient antitumor effects based on PDT- chemotherapy (CT) cascade process. Finally, bright red fluorescence was observed in the tumor cells after internalization implying an application potential in tumor imaging.

Photodynamic therapy (PDT) has been a potential therapeutic method for the treatment of various cancers, with photosensitizer being the key component in photodynamic therapy. In this paper, we prepared a photosensitizer 3-(1-hydroxylethyl)-3-devinyl-131-(dicyanomethylene) pyropheophorbide-a methyl ester (HDCPPa), based on chlorophyll pyropheophorbide-a according to the previous report, and systematically investigated the fluorescence emission spectrum and ultraviolet absorption spectrum HDCPPa has long absorption in the near-infrared spectral region (around 695 nm). The excitation wavelength and the emission wavelength were 415 nm and 699 nm respectively in dichloromethane, 1O2 quantum yield was 63.5%. HDCPPa also had high stability in PBS solution, DMEM cell culture medium and normal saline (NS) in vitro. After irradiation by the light of 675 nm (10 J.cm[Formula: see text]) for 70 min the degradation rate of HDCPPa was 12.5%, which indicated that the target compound showed high stability under light. The in vitrophotodynamic therapy activities against HeLa cells were also studied, which showed that HDCPPa had extremely low dark toxicity but great phototoxicity, and the cell viability is lower than 10% under the light irradiation of 675 nm (10 J.cm[Formula: see text]). Moreover, HDCPPa can quickly enter the cell after being incubated with HeLa cells in less than 30 min. We also evaluated the mechanism of the photochemical reaction, which had proved that Type II is primarily responsible for the cell death. Therefore HDCPPa could serve as a very promising photosensitizer for photodynamic therapy.

Chlorophyll has always been used as the leading compound for photodynamic therapy drug development. In this paper, a novel methyl pyropheophorbide-a- derived photosensitizer, 3-acetyl-3-devinyl-131-dicyanomethylene-pyropheophorbide-a was synthesized through modifications at C-131, C-3, and C-17 positions of methyl pyropheophorbide-a. The compound exhibited a longer wavelength absorption at 713 nm (in methanol) than that of methyl pyropheophorbide-a (667 nm) due to the enlarged the aromatic conjugation system by dicyanomethylene, allowing it to be potential in deep tumor treatment. Moreover, benefiting from the carboxylic group at C-17 and the acetyl group at C-3, the title compound was endowed with better water solubility than that of methyl pyropheophorbide-a. Detailed in vitro photodynamic therapy research showed ADCPPa could be uptaken by cancer cells successfully and killed the cancer cells more efficiently than the leading compound methyl pyropheophorbide-a under light (light dose 10 J/cm2) due to the high singlet oxygen quantum yield (65.98%). The excellent anti-photobleaching ability (degradation rate 1.6% in 10 min) also boosted its potential in practical application. In addition, the research has disclosed that during photochemical processes of photodynamic therapy, the formation of singlet oxygen after photodynamic therapy treatment played a major role, comparing with the formation of superoxide anion and radicals. Finally, the real time quantitative polymerase chain reaction (RT-qPCR) experiments have showed that the target compound has important regulating effect on expression of CDK2 and Survivin, consequently leading to apoptosis and cell death.

Novel antitumor drug methotrexate (MTX) and fluorescence photosensitizer pyropheophorbide-a (PPa) conjugated multifunctional magnetic fluorescence nanoparticles Fe3O4@SiO2–NH2@MTX@PPa (MFMTXPPa) were designed and prepared for chemotherapy, photodynamic therapy (PDT) and medical fluorescence imaging. Fe3O4@SiO2–NH2 nanoparticles were firstly synthesized by a sol–gel process. Then methotrexate and pyropheophorbide-a were successively anchored on the surface of core–shell Fe3O4@SiO2–NH2 nanoparticles via covalently imide bond. The phase structure, composition, morphology, zeta potential, magnetic properties of nanoparticles were characterized by X-ray powder diffraction, Fourier transform infrared spectrometer, transmission electron microscopy, zeta potential, vibration sample magnetometer, thermogravimetric analysis, respectively. Meanwhile, we studied the effect of pH and different polar solvents on the absorption and fluorescence spectrum of MFMTXPPa. Our results indicated that MFMTXPPa preferentially aggregated in the acidic conditions but maintained monomeric form in alkaline conditions. Aggregations exhibit markedly influence on the absorbance and fluorescence intensity. In addition, we found that MFMTXPPa has high magnetization (46.7 emu/g), good water-solubility and dispersity in polar solvents, strong fluorescence intensity in near neutral conditions, and excellent stability in the acid-base system, which may be a potential candidate in the field of chemotherapy, PDT and fluorescence imaging.

Photoinduced single electron transfer (SET) cyclization processes for synthesis of a Sansalvamide A analog containing double pharmacophores (cyclicpeptides and O-phthalimide moiety) is described to develop novel antitumor cyclopeptide drug. The resultant compound is active in drug-sensitive HeLa, HepG-2 and MCF-7 cell lines. Specifically, the title compound was found to inhibit MCF-7 cells with an IC 50 value of 15 μM (13.4 μg/mL), which may serve as a potential candidate for antitumor drug development.

Photodynamic therapy (PDT) is entering the mainstream of the cancer treatments recently. Pyropheophorbide-a (Pa), as a degradation product of chlorophyll-a, has been shown to be a potent photosensitizer in photodynamic therapy. In this paper, we investigated the in vitro photodynamic therapy of 131-ortho-trifluoromethyl-phenylhydrazone modified pyropheophorbide-a (PHPa) against human HeLa cervical cancer cell line, together with ultraviolet-visible spectra, fluorescence emission spectra, stability in various solvents, and single oxygen quantum yield. The results indicated that PHPa not only showed a greater molar extinction coefficient reached 4.55×104 Lmol-1cm-1, the long absorption wavelength (681nm) as we expected that makes it potential in deep tumor treatment, but also showed better stability in near neutral phosphate buffers (pH 7.4) and culture medium, as well as higher single oxygen quantum yield (ФD=40.5%) in DMF solutions. Moreover, cell experiments suggested that PHPa could be uptaken by HeLa cells successfully, and has low dark toxicity without irradiation, but remarkable photo-cytotoxicity (IC50, 1.92±0.59μM) that the inhibition rate of HeLa cells could increase up 91.4% at 30μM of PHPa after irradiation. In addition, morphological changes of HeLa cells further demonstrated that PHPa can induce damage and apoptotic cell death. Furthermore, the mechanism of photochemical processes was investigated by using specific quenching agent sodium azide (SA) and D-mannitol (DM), respectively, which showed the formation of singlet oxygen (Type II reaction mechanism) may play a predominant role, Type I and Type II photodynamic reactions could occur simultaneously in this PHPa mediated PDT process.

In photodynamic therapy (PDT), selection of an ideal photosensitizer and improvement of its photodynamic activities are currently of great interest. In this work, a chlorophyll-a photosensitizer derivative, p-bromo-phenylhydrazone-methyl pyropheophorbide-a (BPMppa) with a long absorption wavelength (683 nm) and a large molar extinction coefficient (7.03 × 104 M−1 cm−1), which is considered to be more suitable for the treatment of deep cancer, is loaded onto pristine graphene using a direct graphite exfoliation process via π–π stacking in water. The obtained graphene loaded photosensitizer G–BPMppa composite shows significantly improved water-solubility and dispersity in water, PBS and culture medium, and an increased singlet oxygen (1O2) quantum yield (ΦΔ = 60.55%) in DMF solution compared to free BPMppa (ΦΔ = 29.2%). In addition, cell experiments indicated that the G–BPMppa composite could be taken up by HeLa cells successfully, showing enhanced intracellular uptake behavior. Owing to its enhanced intracellular uptake and higher 1O2 quantum yield, G–BPMppa showed remarkably improved PDT efficiency (IC50: 1.36 ± 0.35 μg mL−1 of equivalent BPMppa) over free BPMppa after irradiation, but low dark toxicity without irradiation. Moreover, cell morphological changes after G–BPMppa PDT further qualitatively demonstrated that G–BPMppa could induce damage and apoptotic cell death efficiently. Furthermore, the photochemical mechanism of the G–BPMppa mediated PDT process was investigated by using specific quenching agents, sodium azide (SA, a singlet oxygen quencher) and D-mannitol (DM, a hydroxyl radical quencher); the results indicated that type I and type II photodynamic reactions could occur simultaneously, yet the type II reaction (the generation of 1O2) might play a predominant role in the G–BPMppa induced PDT process.

Two novel Fenestin A analogs (1 and 2) containing a phthalimide moiety are prepared by photoinduced cyclization. Their absolute configurations were determined by experimental ECD with the aid of theoretical calculations. The resulting compounds are active in HeLa (IC50 = 28.2 μM for 1 and 36.5 μM for 2) and HepG-2 cell lines (IC50 = 33.5 μM for 1 and 40.3 μM for 2).

Photodynamic therapy (PDT) is a minimally invasive method in cancer treatment and has attracted considerable attention recently. In this paper, we have performed a detailed study of photodynamic activity of a chlorophyllous derivative, Amidochlorin p6 (ACP), and evaluated its potential as a photosensitizer in PDT. The singlet oxygen quantum yield (ΦΔ), the photoreaction mechanisms in PDT, the anti-photobleaching ability in phosphate buffer saline (PBS), the photocytotoxicity and dark toxicity against HeLa cells, cellular uptake and the influence on the expression of survivin and cyclin-dependent kinase (CDK2), were all investigated. The title compound showed significant photocytotoxicity and negligible toxicity in dark, and remarkable photostability. Moreover, ACP could be uptaken by HeLa cells successfully at 20 min leading to damage of cancer cells under light, during which Type I and Type II photodynamic reactions occurred simultaneously on HeLa cells in PDT treatment, and the influence of Type I (the generation of hydroxyl radicals) is slightly larger than Type II (the generation of singlet oxygen). In addition, real-time fluorescent quantitative PCR (RT-qPCR) suggested that ACP could significantly regulate the expression of survivin, which partly explained why ACP could induce the HeLa cell apoptosis and accelerate cell death.

We prepared new folate chitosan conjugated doxorubicin (DOX) and pyropheophorbide acid (PPa) nanoparticles (FCDP–NPs) using an ionic gelation method with tripolyphosphate (TPP) to enhance photodynamic therapy activity, based on the considerations of the long absorption wavelength (683 nm) of pyropheophorbide acid (PPa) in water and the excellent chemotherapeutic characteristics of doxorubicin (DOX) in cancer therapy. The obtained FCDP–NPs demonstrated a typical spherosome structure, a strong near infrared (NIR) absorption (705 nm) and significantly improved stability and dispersity in PBS (pH = 5, 7, 9); as well as a high singlet oxygen quantum yield (ΦΔ = 64%) compared to free PPa (ΦΔ = 59.1%). In addition, the in vitro cell experiments suggested that FCDP–NPs could be uptaken by HepG2 cells quickly and were mainly located in the cell nucleus. FCDP–NPs showed improved PDT efficiency over pure PPa and DOX at the same concentration after irradiation. Specifically, FCDP–NPs could lead to a 92% inhibition rate on HepG2 cells at 40 μg mL−1 (equal to 6 μg mL−1 DOX). However, the pure DOX showed little cytotoxicity at 6 μg mL−1, which suggests that a small amount of DOX could effectively enhance the PDT activities of PPa and lead to little “dark” cytotoxicity. Moreover, cell morphological changes after PDT treatment further indicated that FCDP–NPs could induce damage and apoptotic cell death efficiently. Finally, the photochemical mechanism of FCDP–NPs during PDT process was investigated by using specific quenching agents sodium azide (SA, a single oxygen quencher) and D-mannitol (DM, a hydroxyl radicals quencher), respectively. The results suggested that Type I and Type II photodynamic reactions can occur simultaneously, yet Type I reaction (the generation of hydroxyl radicals) might play a more important role. All these studies indicated that the FCDP–NPs could be potential nanoparticles in photodynamic cancer treatment.

A cyclic analog of natural peptide Yunnanin A was synthesized

Lorlatinib is a third-generation macrocyclic tyrosine kinase inhibitor (TKI) that targets anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) in non-small-cell lung cancer (NSCLC). In this work, an overall structural search of Lorlatinib molecule has been performed by theoretical calculations. The molecular structural optimization, vibrational frequencies, Electronic circular dichroism (ECD) and NMR spectra have been calculated by time-dependence-density functional theory (TD-DFT) using B3LYP method with the 6-311++G(d,p), B3LYP/6-311++G(2d,2p), CAM-B3LYP/TZVP and CAM-ωB97XD/cc-pVDZ basis sets, respectively. IR spectra for Lorlatinib has been recorded in the region of 400–4000 cm−1. 13C and 1H NMR chemical shifts of the molecule was calculated based on the gauge-independent atomic orbital (GIAO) method. All of the calculation results were applied to simulate experimental spectra of the title compound which showed favorable agreement. Furthermore, reliable vibrational assignments which have been made on the basis of potential energy distribution (PED) and characteristic vibrational absorption bands of the title compound in IR spectra have been figured out. Frontier molecular orbitals analysis (FMOs) and the global reactivity descriptors have also been evaluated.

Novel chlorin photosensitizer pyropheophorbide-a (PPA) coated multifunctional magneto-fluorescent nanoparticles Fe3O4@SiO2@CS@PPA (MFCSPPA) about 50 nm in diameter were strategically designed and prepared for photodynamic therapy (PDT) based on the good solubility and magnetic targeting of Fe3O4@SiO2 nanoparticles, excellent biocompatibility and biodegradability of chitosan (CS) polymer, and the unique fluorescence and photodynamic activity of pyropheophorbide-a. In this work, we found that magneto-fluorescent MFCSPPA has high saturation magnetization of 23.7 emu g−1, and showed super-paramagnetic properties, good dispersion in alcohol and water, excellent water-solubility, improved biocompatibility and good photoluminescence properties. In addition, we demonstrated MFCSPPA mediated singlet oxygen production in solution conditions by using 1,3-diphenylisobenzofuran (DPBF) as a fluorescence detector. Moreover, the in vitro PDT activities against human HeLa cervical cancer cells were investigated by MTT assay. The phototoxicity experiments showed that MFCSPPA has strong photodynamic therapy activity and low dark toxicity, and the cancer cell viability was reduced to 18% after treatment with PDT. Phagocytosis of MFCSPPA experiments indicated that it could be successfully taken up to some extent by HeLa cells with a suitable lipo-hydro partition coefficient and biocompatibility. Acridine orange/ethidium bromide (AO/EB) double fluorescence staining suggested that the cells are all in a state of apoptosis or necrosis after PDT treatment for 6 h. In addition, we studied the formation of reactive oxygen species in HeLa cells after MFCSPPA-PDT treatment; the results suggested that type I and type II photodynamic reactions can occur simultaneously, yet type I photodynamic reactions have a slight edge over type II. The as-prepared magneto-fluorescent MFCSPPA nanoparticles are suitable for simultaneous PDT and medical fluorescence imaging.

Novel pyropheophorbide-a-conjugated multifunctional magnetofluorescence nanoparticles Fe3O4@SiO2@APTES@Glutaryl-PPa (MFNPs) with a mean diameter of 50 nm were strategically designed and prepared for photodynamic therapy (PDT) and medical fluorescence imaging. Chlorin photosensitizer pyropheophorbide-a (PPa) was covalently anchored on the surface of core–shell Fe3O4@SiO2@APTES nanoparticles that were prepared via a sol–gel process with a bridging glutaryl group. The phase constitution, morphology, size, chemical properties, magnetic property of the intermediates and final nanoparticles were characterized by X-ray powder diffraction, transmission electron microscopy, Fourier transform infrared spectrometer, zeta potential, vibration sample magnetometer, thermogravimetric analysis, ultraviolet-visible absorption spectra and fluorescent emission spectroscopy. These results showed that the MFNPs have good dispersibility in alcohol and water, excellent magnetization with 17.31 emu g−1 at 300 K, strong superparamagnetic and good photoluminescence property. The in vitro PDT against the human HeLa cervical cancer cell suggested that MFNPs could permeate the tumor cells quickly and possess suitable lipo-hydro partition coefficient, inducing damage and apoptotic cell death. The cancer cell viability was lowered to 10.18% after treatment with PDT. In addition, the formation of reactive oxygen species in HeLa cells after MFNPs-PDT treatment was studied, which suggested that Type I and Type II photodynamic reactions can occur simultaneously.

Cyclic peptides has become an attractive modality for drug development due to their excellent binding affinity, target selectivity and low toxicity, however significant activity difference between the synthetic and natural cyclic peptides such as Phakillestatins has puzzled chemists for years. In an effort to explore the bioactive secondary structures, three pairs of cyclic Phakellistatin 6 analogs with special constrained stereo-features were prepared by regioselectively controlled intramolecular photoinduced single electron transfer (SET) reactions in this paper. The spatial configurationally features were systematically investigated by ECD and NMR, together with detailed structural analysis based on theoretical calculations, which showed that conventional turns rather than irregular γ-/β-turn secondary structures played important roles for the antitumor activities. We also presented the in vitro bioactive assay, liposomal leakage assays and electron microscopy analyses, which indicated the prepared cyclopeptide analogs excellent antitumor activities, most showing greater growth inhibitory effects than that of the famous anticancer agent paclitaxel.