•Zwitterionic zinc phthalocyanines were synthesized.•The influence of zwitteronic structure on phthalocyanine(Pc) has been studied.•The cationic Pc exhibits good photochemical and photophysical properties.•The PDT activity of zwitteronic Pc was weak because of the inner salt formation.Zwitterionic structures were helpful for solubility, cellular uptake and activity for many drugs. But few researches about the influence of zwitterionic structures on phthalocyanine were reported. So, in this work, we design and synthesis a zwitterionic zinc (II) phthalocyanines(ZnPcs). And its solubility, photochemical and photodynamic activity to cancer cells was investigated. Furthermore, these properties of other two ZnPcs, nonionic and cationic ZnPcs with same major structure, were also researched simultaneously. Comparative studies indicated that the zwitterions structures could improve the solubility of ZnPc but greatly reduced its reactive oxygen species (ROSs) generation ability and anti-cancer activity in vitro to nonionic and cationic ZnPcs.A novel zwitterionic sulfobetaine ZS-ZnPc has been synthesized, and the photophysical, photochemical and photobiology properties were compared with other two ZnPcs (NI-ZnPc and CA-ZnPc).

A facile and robust one-pot approach to prepare a theranostic nanoplatform, based on chelation between Gd3+ and hypericin photosensitizer (PS) and their controlled in situ hydrolysis precipitation, was developed. In this strategy, PS drugs and Gd3+ were directly used as building blocks to construct theranostic nanoparticles, resulting in a greatly increased active substance-loading efficiency and ensuring their theranostic effect. The resulting nanoparticles have multifunction capabilities for nuclear magnetic resonance (NMR) imaging and anticancer activity through adenosine triphosphate (ATP) deprivation and heavy atom effect (HAE)-improved photodynamic therapy (PDT) mechanisms.

Photodynamic therapy (PDT) has been applied in cancer treatment by utilizing reactive oxygen species (ROSs) to kill cancer cells. However, a high concentration of reduced glutathione (GSH) is present in cancer cells and can consume ROSs and sharply reduce the PDT activity. To address this problem, herein, we synthesized a thymine modified Zn phthalocyanine (ZnPc, a monomer and an active form for PDT) and prepared its nanoparticle form (an aggregator and an inactive form) with Hg2+ providing the driving force for the “thymine–Hg2+–thymine” interaction. The nanoparticles could remain in the inactive form during the delivery process in blood. Once endocytosed by cancer cells, the nanoparticles are disintegrated, and deprived of Hg2+ by intracellular GSH, which decreases the level of GSH. Simultaneously, the activity of the released monomer ZnPc is recovered and high PDT activity is observed.

Sonodynamic therapy (SDT) is a non-invasive therapeutic modality for cancer treatment. Finding new effective sonosensitizers has attracted great attention in the field of SDT. Mesoporous silica nanoparticles (MSN) have been extensively explored as a drug delivery system because of their good biocompatibility and satisfactory drug loading ability. However, there are relatively few studies devoted to using MSN as an efficient sonosensitizer. In this paper, we found that MSN could be used as an efficient sonosensitizer to induce cell apoptosis after ultrasound (US) treatment. To make the full use of MSN and increase its activity for cancer treatment, a chemotherapeutic drug was encapsulated inside MSN to achieve a chemotherapy-SDT synergistic function. Furthermore, photoinitiated polymerization cross-linked methacrylated hyaluronic acid (m-HA) gel was covered on the surface of DOX@MSN to improve its tumour targeting ability. In vitro and in vivo research studies indicated that the degradation of the m-HA shell by hyaluronidase (HAase) that is concentrated in the tumour environment results in the release of DOX@MSN. Importantly, subsequent US treatment could not only trigger SDT of MSN but also promote DOX release from MSN to show chemotherapeutic activity.

Near-infrared (NIR) light triggered photodynamic therapy (PDT), based on upconversion nanoparticles (UCNPs), has attracted great attention because of its high tissue penetration and low photodamage to living organisms. However, most UCNPs cannot be stably dispersed in aqueous solution and cannot carry photosensitive drugs directly. Besides, UCNP mediated PDT is a fluorescence resonance energy transfer (FRET) process from the UCNPs to the attached photosensitive drugs. So the drug and UCNPs must be stably connected and close enough. In this manuscript, carboxymethyl-β-cyclodextrin (COOH-β-CD) was used to connect UCNPs and adamantine modified phthalocyanine (Ad-ZnPc) through a self-assembly process followed by a host–guest interaction. COOH-β-CD can provide good water solubility of the system and short-distance linking between the UCNPs and Ad-ZnPc. Most importantly, the system has a strong NIR light triggered PDT activity toward cancer cells.

•Cyclodextrins (CD) can form stable 4:1 host-guest complexes with ZnPc.•Three host-guest complexes of ZnPc with α-, β- and γ- CD were prepared and compared.•The interaction mode between ZnPc and various CDs were obvious different.•The anticancer activity of complexes were superior to free ZnPc.•Complex of β-CD and ZnPc has best anticancer activity than two of other complexes.Three host-guest complexes of phthalocyanines (Pc) with α-, β- or γ-cyclodextrins (CDs) were prepared and their interaction modes, reactive oxygen species (ROSs) generation ability and in vitro anticancer activities were studied and compared. After forming complex with CD, the aggregation degree of Pc was greatly decreased and the water solubility and photodynamic activity was sharply increased. Computer modeling results indicated that the interaction modes between Pc and CDs were varied with different kinds of CD. Especially, the complex of Pc and β-CD has superior stability, ROSs generation ability, and anticancer activity to other complexes.

•Charge reversible zinc phthalocyanines substituted with amino acids were prepared.•The isoelectric pHs and charge reversal sensitivity of AAZnPcs were regulated.•The charge of AAZnPcs can be responsive to tumor microenvironment.•Charge reversible GluZnPc and OGluZnPc showed enhanced photodynamic activities.•GluZnPc and OGluZnPc are promising photosensitizers for photodynamic therapy.Amino acid substituted zinc phthalocyanines which are capable of reversing their charge from negative to positive in response to tumor microenvironment have been prepared by the isoelectric pHs regulation and charge reversal sensitivity enhancement. The charge reversal abilities of the prepared zinc phthalocyanines were judged by their isoelectric pHs and zeta potential values. The UV–Vis spectra, singlet oxygen generation ability, cellular uptake and in vitro anticancer ability of the prepared zinc phthalocyanines were investigated to study the influences of charge reversal on photodynamic activities. Charge reversible tetra- and octa-substituted glutamic acid ZnPcs showed enhanced singlet oxygen generation ability, cellular uptake and photocytotoxicity towards cancer cells, and were considered as promising photosensitizers for photodynamic therapy.Amino acid substituted zinc phthalocyanines which are capable of reversing their charge from negative to positive in response to tumor microenvironment have been prepared for photodynamic therapy.

•Two kinds of amino groups modified phthalocyanines were synthesized.•The synthesized phthalocyanine has good water solubility.•Phthalocyanine hydrochloride has high activity which has no extensive applicability.•The substituted amino group type effects photodynamic activity.Many reports indicated that the cellular uptaken and photodynamic anti-cancer activity of amino group modified phthalocyanine (Pc) could be greatly improved in the acid environment around cancer cells because such Pc could transfer to their hydrochloride protonated form and inhibit the intramolecular photoinduced electron transfer (PET) effect. However, no more researches are carried out to indicate whether this law has the extensive applicability in all kinds of amino modified Phthalocyanines (Pcs). So, here, four amino groups modified Pcs and their hydrochloride or quaternized cationic derivatives, with two kinds of amino groups (phenylamine and benzylamine) substituted were synthesized. Their solubility in aqueous system, cancer cell uptaken ability and photodynamic activities were also systematically compared. Our research results indicated that above law had the extensive applicability in benzylamine amino groups modified Pcs. But for phenylamine amino groups modified ones, the cancer cell uptaken ability and anti-cancer activity of hydrochloride derivatives were obviously decreased comparing with the unmodified Pc because its nitrogen atom was closer to the Pc ring, which would induce its nitrogen atom and the ring to form p–π conjugation system, furthermore, the relatively free state of lone pair electrons of surrounding nitrogen atom leaded to PET strengthening.Two kinds of amino groups (phenylamine and benzylamine) modified Pcs and their hydrochloride or quaternized derivatives were designed and synthesized. The substituted amino group type dependent sensitivity enhancing of cationic phthalocyanine derivatives for photodynamic activity was showed.

•Charge photosensitive drug can self-assemble by regulating environment ion strength.•Self-assemble degree can be controlled by ion strength.•Nanostructures with proper assemble degree have superior activity to monomers.Self-assembled organic photosensitive nanoparticles have been widely used in diagnosis and therapeutic of cancer. In this manuscript, a simple but effective method to regulate the self-assemble degree of small charge photosensitive drug was demonstrated. Studies indicated that the ordered self-assembled nanostructures with proper assemble degree can significantly enhances the reactive oxygen species generation efficiency and, thereby, improve the in vitro photodynamic efficacy comparing with the corresponding monomers.A simple but effective method to regulate the self-assemble degree of small charge photosensitive drug was demonstrated to improve its photodynamic activity.

•Zinc phthalocyanines with different quaternized ammonium groups were synthesized.•Zinc phthalocyanines with different configuration were synthesized.•The number of quaternized nitrogens influences the properties of phthalocyanines.•Configuration of quaternized nitrogens influences the properties of phthalocyanines.The influences of the number of the ammonium groups and their arrangement manner on the photophysical properties of the quaternized zinc phthalocyanines were studied. The aggregation tendency, singlet oxygen generation ability and the fluorescence intensity properties of the quaternized zinc phthalocyanines were studied and compared. Results indicated that more quaternized ammonium groups and the straight chain arrangement manner for the quaternized zinc phthalocyanines can decrease aggregation degree and increase singlet oxygen generation and fluorescence intensity.Four quaternized zinc phthalocyanines with different ammonium groups and configuration for quaternized nitrogens were synthesized and studied. Result showed that the straight configuration and the increased numbers of quaternized ammonium groups can decrease the aggregation degree and improve the single oxygen generation ability and fluorescence intensity.

•The complex of two anticancer drugs, hypocrellin A (HA) and Ga(NO3)3, is prepared.•The complex can be effectively taken up by cancer cells.•Anticancer results show the combined effect of both HA and Ga(NO3)3 for the complex.Combining different treatment modalities is widely employed in oncology to improve the therapeutic response. In this work, we develop a multifunctional complex for co-delivery of the anticancer drug Ga(NO3)3 and the photosensitizer hypocrellin A (HA) as potential dual delivery system for the combination of chemotherapy and photodynamic therapy (PDT). Ga(NO3)3 is used in cancer treatment and is synergistic with other anticancer drugs. Hypocrellin A is a natural photosensitizer, which has been extensively and intensively studied as a promising PDT agent. HA can chelate with gallium ion to form a 1:1 complex. Irradiation of the complex with light of suitable wavelength results in efficient generation of singlet oxygen (1O2). In vitro studies have demonstrated the active uptake of the complex into the cytosol of tumor cells. Viability of cells treated with the complex decreased as compared to free HA or Ga(NO3)3, thus showing a combined effect of both HA and Ga(NO3)3.

The stable 4:1 host–guest complex of phthalocyanine (Pc) and hydroxypropyl-beta-cyclodextrin was designed, computer modeled and prepared. The complex formation can greatly increase water solubility, reactive oxygen generation ability, biocompatibility and, thereby, the in vitro phototoxicity of Pc to cancer cells.

•Zinc phthalocyanines of differing protonation degree were prepared.•Protonation degree can influence 1O2 generation ability of phthalocyanines.•Protonation degree influences the photodynamic activity of phthalocyanines.This work reports on the effects of protonation degree on the photodynamic activity of zinc phthalocyanine substituted with 1,2-diethylamino (ZnPc1). Photophysical properties, singlet oxygen generation ability and photodynamic anticancer activity of derivatives of ZnPc1 with different protonation degree were studied and compared. Results indicated that the protonation degree can greatly influence the photophysical and photochemical properties of ZnPc1, thereby affecting its photodynamic activity. When the mole ratio of ZnPc1 and hydrochloric acid (HCl) was 1:8, the derivative of ZnPc1 showed the best photodynamic activity.Derivatives of ZnPc1 with different protonation degree were prepared. There is a close relationship between protonation degree and photodynamic activity. Protonation degree can influence the photophysical and photochemical properties of ZnPc1, thereby affecting its photodynamic activity.

The complex of Hypocrellin A with Al3+ is prepared in water solution by a facile method. The water-solubility and stability of complexes are improved. Irradiation of Al3+–HA complex results in higher efficient generation of singlet oxygen (1O2) and photocleavage ability to CT DNA than HA. In vitro studies have illustrated that the Al3+–HA complex has anti-cancer activity.

Interaction studies of the vanadyl-hypocrellin A (VO2+-HA) complex and hypocrellin A (HA) with CT DNA were investigated by UV–Vis spectroscopy, DNA melting, fluorescence spectra and zeta potential measurements. The binding constants and binding mechanisms of HA and VO2+-HA with CT DNA had also been studied by fluorescence quenching experiments. Both spectrophotometric and DNA melting studies indicated that VO2+-HA and HA could bind to CT DNA. Thermodynamic parameters together with zeta potential studies revealed that the binding force between HA or VO2+-HA with CT DNA was hydrophobic and electrostatic force, separately.Highlights► VO2+-HA complex and HA could both bind to CT DNA.► The fluorescence quenching mechanisms by VO2+-HA or HA were static quenching.► The binding force between HA and CT DNA was hydrophobic force.► The binding force between VO2+-HA and CT DNA was electrostatic force.

Hypocrellin A is an efficient photodynamic agent against many tumor cells and viruses. However, it was found that the preparation of injectable formula for HA was highly hampered by the poor water solubility of these compounds. So, here, a new water-soluble vanadyl–hypocrellin A complex was first synthesized and the complex forming process was studied using spectral and thermal dynamics methods. The results indicated that VO2+–HA can stable in aqueous solutions and exhibit increased photostability, affinity and photocleavage ability toward ctDNA under anaerobic condition. Moreover, in vitro studies illustrated that VO2+–HA also had strong anti-cancer activity.Structure for the vanadyl–hypocrellin A complex and cell survival curves for HeLa cells exposed to various concentrations of the drug (a) VOSO4; (b) HA; (c) VO2+–HA.A new water-soluble vanadyl–hypocrellin A complex (VO2+–HA) was first prepared. All results showed that VO2+–HA can stable in aqueous solutions and exhibit increased photostability, affinity and photocleavage ability toward ctDNA under anaerobic condition. Moreover, in vitro studies illustrated that VO2+–HA also had strong anti-cancer activity.

A facile and robust one-pot approach to prepare a theranostic nanoplatform, based on chelation between Gd3+ and hypericin photosensitizer (PS) and their controlled in situ hydrolysis precipitation, was developed. In this strategy, PS drugs and Gd3+ were directly used as building blocks to construct theranostic nanoparticles, resulting in a greatly increased active substance-loading efficiency and ensuring their theranostic effect. The resulting nanoparticles have multifunction capabilities for nuclear magnetic resonance (NMR) imaging and anticancer activity through adenosine triphosphate (ATP) deprivation and heavy atom effect (HAE)-improved photodynamic therapy (PDT) mechanisms.

Near-infrared (NIR) light triggered photodynamic therapy (PDT), based on upconversion nanoparticles (UCNPs), has attracted great attention because of its high tissue penetration and low photodamage to living organisms. However, most UCNPs cannot be stably dispersed in aqueous solution and cannot carry photosensitive drugs directly. Besides, UCNP mediated PDT is a fluorescence resonance energy transfer (FRET) process from the UCNPs to the attached photosensitive drugs. So the drug and UCNPs must be stably connected and close enough. In this manuscript, carboxymethyl-β-cyclodextrin (COOH-β-CD) was used to connect UCNPs and adamantine modified phthalocyanine (Ad-ZnPc) through a self-assembly process followed by a host–guest interaction. COOH-β-CD can provide good water solubility of the system and short-distance linking between the UCNPs and Ad-ZnPc. Most importantly, the system has a strong NIR light triggered PDT activity toward cancer cells.