Phthalocyanine aggregates as semiconductor-like photocatalysts for hypoxic-tumor photodynamic immunotherapy.

Photodynamic immunotherapy (PIT) has emerged as a promising approach for efficient eradication of primary tumors and inhibition of tumor metastasis. However, most of photosensitizers (PSs) for PIT exhibit notable oxygen dependence. Herein, a concept emphasizing on transition from molecular PSs into semiconductor-like photocatalysts is proposed, which converts the PSs from type II photoreaction to efficient type I photoreaction.

A tumor-pH-responsive phthalocyanine as activatable type I photosensitizer for improved photodynamic immunotherapy.

The development of a simple drug formulation capable of achieving both activatable type I photoreaction and tumor-responsive release of immunomodulator is crucial for advancing photodynamic immunotherapy (PDIT). Herein, we present a nanostructured photosensitizer (NP5) that is activated by the acidic tumor microenvironment to produce type I reactive oxygen species (ROS) under light irradiation and release the immunomodulator demethylcantharidin (DMC) for PDIT. The NP5 is formed by self-assembly of a versatile phthalocyanine molecule which is composed of DMC and phthalocyanine linked via a pH-responsive amide bond.

A smart and visible way to switch the aromaticity of silicon(IV) phthalocyanines.

Unlike traditional methods of modifying phthalocyanines (Pcs), we herein report a smart and visible way to switch the aromaticity of silicon(IV) phthalocyanines a reversible nucleophilic addition reaction of the Pc skeleton induced by alkalis and acids, leading to an interesting allochroism phenomenon and the switching of photosensitive activities.

A Sulfur-Bridging Sulfonate-Modified Zinc(II) Phthalocyanine Nanoliposome Possessing Hybrid Type I and Type II Photoreactions with Efficient Photodynamic Anticancer Effects.

Phthalocyanines are potentially promising photosensitizers (PSs) for photodynamic therapy (PDT), but the inherent defects such as aggregation-caused quenching effects and non-specific toxicity severely hinder their further application in PDT. Herein, we synthesized two zinc(II) phthalocyanines (PcSA and PcOA) monosubstituted with a sulphonate group in the alpha position with "O bridge" and "S bridge" as bonds and prepared a liposomal nanophotosensitizer (PcSA@Lip) by thin-film hydration method to regulate the aggregation of PcSA in the aqueous solution and enhance its tumor targeting ability. PcSA@Lip exhibited highly efficient production of superoxide radical (O) and singlet oxygen (O) in water under light irradiation, which were 2.

Thermosensitive Liposomal Nanoplatform Based on Metal-Free Phthalocyanine with Copper(II)-Regulated Photoactivities.

This work reports the development of a multifunctional thermosensitive liposomal nanoplatform (PcS@Lip-FA) based on a metal-free phthalocyanine modified with tetra-sulfonates (PcPS), which exhibited photodynamic and photothermal activities simultaneously. Upon irradiation with a near infrared laser, thermosensitive PcS@Lip-FA could release PcS as a result of the local hyperthermia of PcS. Interestingly, PcS could easily chelate with Cu, leading to the enhancement of photothermal activity and decrease of photodynamic activity.

Molecular and Supramolecular Approach to Highly Photocytotoxic Phthalocyanines with Dual Cell Uptake Pathways and Albumin-Enhanced Tumor Targeting.

Phototherapy for non-invasive cancer treatment has been extensively studied. An urgent challenge in phototherapy application is to fabricate appropriate targeted agents to achieve efficient therapeutic effect. Herein, a molecular and supramolecular approach for targeting phototherapy was reasonably designed and realized through the axial sulfonate modification of silicon(IV) phthalocyanines (Pcs), followed by supramolecular interaction with albumin.

Aggregation-Enhanced Sonodynamic Activity of Phthalocyanine-Artesunate Conjugates.

The clinical prospect of sonodynamic therapy (SDT) has not been fully realized due to the scarcity of efficient sonosensitizers. Herein, we designed phthalocyanine-artesunate conjugates (e.g.

Nanostructured Phthalocyanine Assemblies with Efficient Synergistic Effect of Type I Photoreaction and Photothermal Action to Overcome Tumor Hypoxia in Photodynamic Therapy.

Most photodynamic therapy (PDT) paradigms work through the highly O-dependent type II photoreaction to generate singlet oxygen (O). The hypoxic microenvironment of solid tumors severely hampers therapeutic outcomes. Here, we present a novel design that could transfer the photophysical and photochemical properties of traditional phthalocyanine-based photosensitizers from type II photoreaction to efficient type I photoreaction and vibrational relaxation-induced photothermal conversion.

A pH-sensitive nanoagent self-assembled from a highly negatively-charged phthalocyanine with excellent biosafety for photothermal therapy.

Photothermal therapy (PTT) is a promising strategy for cancer treatment. However, the development of highly efficient photothermal agents with excellent biosafety, particularly with low liver retention, is very meaningful for clinical applications, but it is also challenging. We herein prepared a pH-sensitive nanoagent (NanoPc3) by the self-assembly of a zinc(ii) phthalocyanine substituted with hexadeca-sulphonates linked by hydrazone bonds for photoacoustic imaging and PTT.

A phthalocyanine-based self-assembled nanophotosensitizer for efficient in vivo photodynamic anticancer therapy.

To develop highly efficient photosensitizers for photodynamic therapy, herein a zinc(II) phthalocyanine-folate conjugate (PcN-FA) used to construct an activatable nanophotosensitizer (NanoPcN-FA) through a facile self-assembly. The self-assembled nanophotosensitizer (NanoPcN) without folate-modification was used as a negative control. After self-assembly, the photoactivities of NanoPcN-FA was quenched.

A non-aggregated zinc(II) phthalocyanine with hexadeca cations for antitumor and antibacterial photodynamic therapies.

With a view to developing highly efficient photosensitizers for both antitumor and antimicrobial photodynamic therapies, herein, we reported a super cationic zinc(II) phthalocyanine (Pc4), which was prepared through the quaternization of the N, N-dimethyl-3-aminophenoxyl-hexadeca-substituted precursor Pc3. Meanwhile, two disubstituted analogues (Pc1 and Pc2) were also prepared as controls. The cationic Pc2 and Pc4 had higher photoactivities including fluorescence and singlet oxygen than the neutral counterparts Pc1 and Pc3, probably because of the inhibition of intramolecular charge transfer (ICT) effect of the amino groups.

Artesunate-Based Multifunctional Nanoplatform for Photothermal/Photoinduced Thermodynamic Synergistic Anticancer Therapy.

Thermodynamic therapy (TDT), one that uses heat to activate thermosensitizers and produce reactive oxygen species (ROS), has recently emerged as an attractive approach for cancer therapy. However, the development of safe and efficient thermosensitizers for TDT remains a big challenge. Here, we have found that artesunate (ARS) could produce ROS upon heating.

Monosubstituted tricationic Zn(II) phthalocyanine enhances antimicrobial photodynamic inactivation (aPDI) of methicillin-resistant (MRSA) and cytotoxicity evaluation for topical applications: and study.

Antimicrobial photodynamic therapy (aPDT) is an innovative approach to combat multi-drug resistant bacteria. It is known that cationic Zn(II) phthalocyanines (ZnPc) are effective in mediating aPDT against methicillin-resistant (MRSA). Here we used ZnPc-based photosensitizer named ZnPcE previously reported by our research group to evaluate its aPDT efficacy against broad spectrum of clinically relevant MRSAs.

Alginate-zinc (II) phthalocyanine conjugates: Synthesis, characterization and tumor-associated macrophages-targeted photodynamic therapy.

Tumor-associated macrophages (TAMs)-targeted photodynamic therapy (PDT) has dual-selectivity and hence is promising in cancer treatment. Since the scavenger receptor-A (SR-A) on TAMs can recognize polyanions, two molecular-weight sodium alginates (SA1, 41.2 kDa; SA2, 1231.

A non-aggregated silicon(IV) phthalocyanine-lactose conjugate for photodynamic therapy.

To develop a highly efficient photosensitizer for photodynamic therapy (PDT), we have designed and synthesized a phthalocyanine-lactose conjugate (Pc-Lac) through axial modification of silicon(IV) phthalocyanine with lactose moieties. With the lactose substituents, Pc-Lac is highly hydrophilic and non-aggregated with efficient reactive oxygen species (ROS) generation in aqueous media. With these desirable properties, Pc-Lac shows high photocytotoxicity and cellular uptake toward HepG2 cells.

Noncovalent Indocyanine Green Conjugate of C-Phycocyanin: Preparation and Tumor-Associated Macrophages-Targeted Photothermal Therapeutics.

Fabrication of a multifunctional near-infrared (NIR) theranostic nanoplatform has attracted increasing attention. Indocyanine green (ICG), a clinic-approved NIR fluorescence-imaging agent, is an excellent photothermal agent candidate. However, the stability and tumor targeting are still great obstacles for its wide application.

Carboxymethyl chitosan-zinc(II) phthalocyanine conjugates: Synthesis, characterization and photodynamic antifungal therapy.

Photodynamic antifungal therapy is a promising treatment for increasing drug-resistant fungi. However, low physiological solubility and low fungi-affinity of most potential photosensitizers limits their therapeutic efficacy. To improve the water-solubility and photodynamic antifungal activity of zinc(II) phthalocyanine, two molecular-weight carboxymethyl chitosans (CMC1,50 kDa; CMC2,170 kDa) were herein respectively conjugated with 1-[4-(2-aminoethyl)phenoxy] zinc(II) phthalocyanine (ZnPcN) and further quaternized, and eight novel conjugates were obtained and characterized.

Size-Tunable Targeting-Triggered Nanophotosensitizers Based on Self-Assembly of a Phthalocyanine-Biotin Conjugate for Photodynamic Therapy.

Self-assembled phototheranostic nanomaterials used for photodynamic therapy (PDT) have attracted increasing attention owing to their several advantages. Herein, we developed a novel strategy for size-tunable self-assembled nanophotosensitizers for PDT through a simple method. A series of switchable self-assembled nanophotosensitizers (, , , and ) of different particle sizes were readily prepared based on an amphiphilic silicon(IV) phthalocyanine (SiPc)-biotin conjugate by regulating the amount of the Cremophor EL surfactant used.

A pH-responsive stellate mesoporous silica based nanophotosensitizer for in vivo cancer diagnosis and targeted photodynamic therapy.

Development of a photosensitizer that can achieve tumor specificity, improve therapeutic efficacy, and reduce side effects remains a challenge for photodynamic therapy (PDT). In this work, a pH-sensitive activatable nanophotosensitizer (SMSN-ZnPc1) has been elaborately designed, which could be readily prepared by using a functionalized zinc(ii) phthalocyanine (ZnPc) to conjugate with stellate mesoporous silica nanoparticles (SMSNs) through an acid-sensitive hydrazone bond. Meanwhile, a non-activatable analogue SMSN-ZnPc2 has also been prepared as a negative control.

Synthesis and photodynamic activities of integrin-targeting silicon(IV) phthalocyanine-cRGD conjugates.

A series of novel symmetric or unsymmetric silicon (IV) phthalocyanines axially substituted with cyclic Arg-Gly-Asp (cRGD) ligands through different ethylene glycol chains have been synthesized by a facile and mild "click" reaction. All the compounds show efficient photosensitizing activities in N,N-dimethylformamide, and are essentially non-aggregated in RPMI 1640 medium with 0.05% Cremophor EL.

Progress in the development of nanosensitizers for X-ray-induced photodynamic therapy.

In recent years, photodynamic therapy has been applied in cancer treatment because of its high selectivity and marginal invasion properties. However, the excitation light used has limited ability to penetrate tissue, which creates a stumbling block for its future development. To overcome this, X-rays have been introduced to transmit energy to deeper tissues.

New application of phthalocyanine molecules: from photodynamic therapy to photothermal therapy by means of structural regulation rather than formation of aggregates.

Phthalocyanine (Pc) molecules exhibit high extinction coefficients in near-infrared region, rendering them well-suited for phototherapies, but most of their applications are limited to the field of photodynamic therapy (PDT). Herein, for the first time, we illustrate that Pc molecules can be endowed with excellent photothermal properties by means of structural regulation rather than formation of aggregates. Three representative Pc derivatives show efficient activities of photothermal therapy (PTT) against human hepatocellular carcinoma cells.

Facile Supramolecular Approach to Nucleic-Acid-Driven Activatable Nanotheranostics That Overcome Drawbacks of Photodynamic Therapy.

Supramolecular chemistry provides a "bottom-up" method to fabricate nanostructures for biomedical applications. Herein, we report a facile strategy to directly assemble a phthalocyanine photosensitizer (PcS) with an anticancer drug mitoxantrone (MA) to form uniform nanostructures (PcS-MA), which not only display nanoscale optical properties but also have the capability of undergoing nucleic-acid-responsive disassembly. These supramolecular assemblies possess activatable fluorescence emission and singlet oxygen generation associated with the formation of free PcS, mild photothermal heating, and a concomitant chemotherapeutic effect associated with the formation of free MA.

A Tumor-pH-Responsive Supramolecular Photosensitizer for Activatable Photodynamic Therapy with Minimal Skin Phototoxicity.

A major challenge in photodynamic therapy (PDT) is the development of new tumor-targeting photosensitizers. The tumor-specific activation is considered to be an effective strategy for designing these photosensitizers. Herein, we describe a novel tumor-pH-responsive supramolecular photosensitizer, LDH-ZnPcS, which is not photoactive under neutral conditions but is precisely and efficiently activated in a slightly acidic environment (pH 6.

C-Phycocyanin as a tumour-associated macrophage-targeted photosensitiser and a vehicle of phthalocyanine for enhanced photodynamic therapy.

C-Phycocyanin (CPC) as a tumour-associated macrophage (TAM)-targeted photosensitiser has been first proved, and used as a vehicle of zinc phthalocyanine (ZnPc) to fabricate a ZnPc-CPC conjugate, which exhibits an efficient in vitro photodynamic activity, and selectively accumulates in tumour sites probably due to the affinity to TAM.