A Nanoencapsulated Ir(III)-Phthalocyanine Conjugate as a Promising Photodynamic Therapy Anticancer Agent.

Despite the potential of photodynamic therapy (PDT) in cancer treatment, the development of efficient and photostable photosensitizing molecules that operate at long wavelengths of light has become a major hurdle. Here, we report for the first time an Ir(III)-phthalocyanine conjugate (Ir-ZnPc) as a novel photosensitizer for high-efficiency synergistic PDT treatment that takes advantage of the long-wavelength excitation and near infrared (NIR) emission of the phthalocyanine scaffold and the known photostability and high phototoxicity of cyclometalated Ir(III) complexes. In order to increase water solubility and cell membrane permeability, the conjugate and parent zinc phthalocyanine (ZnPc) were encapsulated in amphoteric redox-responsive polyurethane-polyurea hybrid nanocapsules (Ir-ZnPc-NCs and ZnPc-NCs, respectively). Photobiological evaluations revealed that the encapsulated Ir-ZnPc conjugate achieved high photocytotoxicity in both normoxic and hypoxic conditions under 630 nm light irradiation, which can be attributed to dual Type I and Type II reactive oxygen species (ROS) photogeneration. Interestingly, PDT treatments with Ir-ZnPc-NCs and ZnPc-NCs significantly inhibited the growth of three-dimensional (3D) multicellular tumor spheroids. Overall, the nanoencapsulation of Zn phthalocyanines conjugated to cyclometalated Ir(III) complexes provides a new strategy for obtaining photostable and biocompatible red-light-activated nano-PDT agents with efficient performance under challenging hypoxic environments, thus offering new therapeutic opportunities for cancer treatment.

Exceptional anticancer photodynamic properties of [1,4-Bis(3,6,9,12-Tetraoxatridec-1-yloxy)phthalocyaninato]zinc(II).

Phthalocyanines have been described as effective photosensitizers for photodynamic therapy and are therefore, being studied for their biomedical applications. The metalation of photosensitizers can improve their photodynamic therapy potential. Here, we focus on the biological properties of [1,4-Bis(3,6,9,12-Tetraoxatridec-1-yloxy)phthalocyaninato]zinc(II) (ZnPc(αEG4)2) and demonstrate its exceptional anticancer activity upon light stimulation to kill preferentially cancer cells with a start of efficiency at 10 pM. Indeed, in this work we highlighted the high selectivity of ZnPc(αEG4)2 for cancer cells compared with healthy ones and we establish its mechanism of action, enabling us to conclude that ZnPc(αEG4)2 could be a powerful tool for cancer therapy.

Formation and Photoinduced Electron Transfer in Porphyrin- and Phthalocyanine-Bearing N-Doped Graphene Hybrids Synthesized by Click Chemistry.

Graphene doped with heteroatoms such as nitrogen, boron, and phosphorous by replacing some of the skeletal carbon atoms is emerging as an important class of two-dimensional materials as it offers the much-needed bandgap for optoelectronic applications and provides better access for chemical functionalization at the heteroatom sites. Covalent grafting of photosensitizers onto such doped graphenes makes them extremely useful for light-induced applications. Herein, we report the covalent functionalization of N-doped graphene (NG) with two well-known electron donor photosensitizers, namely, zinc porphyrin (ZnP) and zinc phthalocyanine (ZnPc), using the simple click chemistry approach. Covalent attachment of ZnP and ZnPc at the N-sites of NG in NG-ZnP and NG-ZnPc hybrids was confirmed by using a range of spectroscopic, thermogravimetric and imaging techniques. Ground- and excited-state interactions in NG-ZnP and NG-ZnPc were monitored by using spectral and electrochemical techniques. Efficient quenching of photosensitizer fluorescence in these hybrids was observed, and the relatively easier oxidations of ZnP and ZnPc supported excited-state charge-separation events. Photoinduced charge separation in NG-ZnP and NG-ZnPc hybrids was confirmed by using the ultrafast pump-probe technique. The measured rate constants were of the order of 1010  s,-1 thus indicating ultrafast electron transfer phenomena.

Photodynamic Inactivation of Antibiotic-Resistant and Sensitive Aeromonas hydrophila with Peripheral Pd(II)- vs. Zn(II)-Phthalocyanines.

The antimicrobial multidrug resistance (AMR) of pathogenic bacteria towards currently used antibiotics has a remarkable impact on the quality and prolongation of human lives. An effective strategy to fight AMR is the method PhotoDynamic Therapy (PDT). PDT is based on a joint action of a photosensitizer, oxygen, and light within a specific spectrum. This results in the generation of singlet oxygen and other reactive oxygen species that can inactivate the pathogenic cells without further regrowth. This study presents the efficacy of a new Pd(II)- versus Zn(II)-phthalocyanine complexes with peripheral positions of methylpyridiloxy substitution groups (pPdPc and ZnPcMe) towards Gram-negative bacteria Aeromonas hydrophila (A.hydrophila). Zn(II)-phthalocyanine, ZnPcMe was used as a reference compound for in vitro studies, bacause it is well-known with a high photodynamic inactivation ability for different pathogenic microorganisms. The studied new isolates of A.hydrophila were antibiotic-resistant (R) and sensitive (S) strains. The photoinactivation results showed a full effect with 8 µM pPdPc for S strain and with 5 µM ZnPcMe for both R and S strains. Comparison between both new isolates of A.hydrophila (S and R) suggests that the uptakes and more likely photoinactivation efficacy of the applied phthalocyanines are independent of the drug sensitivity of the studied strains.

BSA/DNA binding behavior and the photophysicochemical properties of novel water soluble zinc(II)phthalocyanines directly substituted with piperazine groups.

In the current research, two novel zinc(II) phthalocyanines (ZnPcs) (1 and 2) directly connecting with 4-(4-methylpiperazin-1-yl)phenyl groups have been synthesized through the Suzuki-Miyaura coupling reaction. These ZnPcs 1 and 2 were converted to their water-soluble derivatives (1Q and 2Q) by quaternization. The photochemical and photophysical properties were determined in DMSO for the non-ionic zinc(II) phthalocyanines (1 and 2) and in both DMSO and aqueous solutions for the quaternized cationic derivatives (1Q and 2Q) to establish their photosensitizer capabilities in photodynamic therapy (PDT). The spectrofluorometric and spectrophotometric techniques were employed for the determination of interaction between water-soluble ZnPcs (1Q and 2Q) and BSA or ct-DNA. The binding constants of these compounds to BSA were found in the order of 108 M-1. The binding constant of the ct-DNA interaction with 2Q (1.09 × 105 M-1) was found higher than 1Q (6.87 × 104 M-1). The thermodynamic constants were determined for both 1Q and 2Q. The endothermic and spontaneous nature of interaction was observed with ct-DNA. Besides, the thermal denaturation and viscosity studies proved the non-intercalative mode of binding for both compounds to ct-DNA.

Promising photodynamic antimicrobial activity of polyimine substituted zinc phthalocyanine and its polycationic derivative when conjugated to nitrogen, sulfur, co-doped graphene quantum dots against Staphylococcus aureus.

Antimicrobial resistance is a most important problem facing the treatment of infectious diseases. Antimicrobial photodynamic therapy is an alternative treatment strategy, considered to be cost-effective and feasible. For this purpose, octa-imine substituted ZnPc (3) have been prepared and conjugated to nitrogen, sulfur co-doped graphene quantum dots (N,S-GQDs) through π-π stacking. The photophysical and photochemical properties of Pc alone and and Pc-conjugated to the GQD nanomaterial such as absorption, fluorescence, fluorescence life time, singlet oxygen quantum yields, triplet state quantum yields and exited state lifetimes were investigated in solutions before in vitro cell studies. The PACT activity of prepared structures was investigated against Gram-positive (Staphylococcus aureus). Our results suggest that the in the case of conjugation of zinc Pc to N,S-GQDs, photodynamic inactivation increased with the 100 % reduction percentage.

Zinc(II) phthalocyanines as photosensitizers for antitumor photodynamic therapy.

Photodynamic therapy (PDT) is a highly specific and clinically approved method for cancer treatment in which a nontoxic drug known as photosensitizer (PS) is administered to a patient. After selective tumor irradiation, an almost complete eradication of the tumor can be reached as a consequence of reactive oxygen species (ROS) generation, which not only damage tumor cells, but also lead to tumor-associated vasculature occlusion and the induction of an immune response. Despite exhaustive investigation and encouraging results, zinc(II) phthalocyanines (ZnPcs) have not been approved as PSs for clinical use yet. This review presents an overview on the physicochemical properties of ZnPcs and biological results obtained both in vitro and in more complex models, such as 3D cell cultures, chicken chorioallantoic membranes and tumor-bearing mice. Cell death pathways induced after PDT treatment with ZnPcs are discussed in each case. Finally, combined therapeutic strategies including ZnPcs and the currently available clinical trials are mentioned.

Targeted photodynamic therapy of breast cancer cells using lactose-phthalocyanine functionalized gold nanoparticles.

Gold nanoparticles (AuNPs), which have been widely used for the delivery of photosensitizers for photodynamic therapy (PDT) of cancer, can be dispersed in aqueous solutions improving the delivery of the hydrophobic photosensitizer into the body. Furthermore, the large surface of AuNPs can be functionalized with a variety of ligands, including proteins, nucleic acids and carbohydrates, that allow selective targeting to cancer tissue. In this study, gold nanoparticles were functionalized with a mixed monolayer of a zinc phthalocyanine and a lactose derivative. For the first time, a carbohydrate was used with a dual purpose, as the stabilizing agent of the gold nanoparticles in aqueous solutions and as the targeting agent for breast cancer cells. The functionalization of the phthalocyanine-AuNPs with lactose led to the production of water-dispersible nanoparticles that are able to generate singlet oxygen and effect cell death upon irradiation. The targeting ability of lactose of the lactose-phthalocyanine functionalized AuNPs was studied in vitro towards the galectin-1 receptor on the surface of breast cancer cells. The targeting studies showed the exciting potential of lactose as a specific targeting agent for galactose-binding receptors overexpressed on breast cancer cells.

Combining electron-accepting phthalocyanines and nanorod-like CuO electrodes for p-type dye-sensitized solar cells.

A route is reported for the synthesis of two electron-accepting phthalocyanines featuring linkers with different lengths as sensitizers for p-type dye-sensitized solar cells (DSSCs). Importantly, our devices based on novel nanorod-like CuO photocathodes showed high efficiencies of up to 0.191 %: the highest value reported to date for CuO-based DSSCs.