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.

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.

An effective theranostic platform based on porous silica nanoparticles encapsulated with the complex of a photodynamic anticancer drug and graphene quantum dots (GQDs), with the bifunction of multicolor imaging and satisfactory photo-induced anticancer activity, was successfully designed and prepared for in vitro photodynamic therapy (PDT) of superficial cancer.

•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.

A series of hypocrellin A (HA) self-assembled nanostructures were prepared by controlling the charge properties of drugs and the ion strength of the environment. Comparative studies with nanostructures and HA have demonstrated that the self-assembled effect on the HA molecule significantly enhances its water dispersion ability, 1O2 generation efficiency and, thereby, the in vitro phototoxicity to human cervical carcinoma (HeLa) cells.

•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.

•PG intercalated into the DNA helix.•The binding of PG and ct-DNA are partial intercalation mode.•Van der Waals forces are mainly between PG and ct-DNA in the present of EB.•The interaction follows the static quenching mechanism.The interaction between prodigiosin (PG) and calf thymus DNA (ct-DNA) was investigated firstly by using UV–Visible (UV–Vis), fluorescence, Fourier transform infrared (FT-IR), circular dichroism (CD) spectroscopies and viscosity measurement in Tris–HCl buffer solution (pH 6.8). The experimental results indicated that PG intercalated into the DNA helix. Upon addition of ct-DNA, PG showed hypochromic effect and slight redshift in the absorption spectra, and the melting temperature of ct-DNA was increased by from 58 to 64 °C. Furthermore, FT-IR spectrum and CD spectra also suggested that the partial bases of ct-DNA react with prodigiosin. The fluorescence quenching mechanism was studied using ethidium bromide as a DNA probe, The binding constants of PG with ct-DNA in the presence of EB are 4.46 × 104 and 2.32 × 104 M−1 at 298 and 310 K, respectively, and the corresponding thermodynamic parameters ΔG, ΔH, ΔS at various temperatures were obtained.

•DHA and 9-OH DHA both induce the heme group of BHb.•DHA and 9-OH DHA both can change the polarity of BHb.•DHA and 9-OH DHA both make BHb unfolding.•The interaction between BHb and DHA is stronger than 9-OH DHA.The UV–vis absorption, steady state/time resolved fluorescence spectroscopy and synchronous fluorescence, circular dichroism (CD) spectroscopy are used to investigate the interaction mechanisms of dihydroartemisinin (DHA) and 9-hydroxy-dihydroartemisinin (9-OH DHA), respectively. The UV–vis studies present that DHA and 9-OH DHA can disturb the structure of bovine hemoglobin (BHb). Steady state/time resolved and synchronous fluorescence spectroscopy reveal that the binding constant of DHA with BHb is bigger than 9-OH DHA. CD spectra indicate DHA and 9-OH DHA can change the conformation of BHb. The comparison results suggest that the binding of BHb with DHA is more stable and stronger than 9-OH DHA.Graphical abstract

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.

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.

In this study, the chelation of Hypocrellin A (HA) with Al3+ in water solution has been synthesized, and the interactions of HA and Al3+–HA complex with calf thymus DNA are in detail compared by UV–vis and fluorescence spectroscopic techniques, circular dichroism spectroscopy and viscosity measurement. The experiment results suggest that HA and Al3+–HA complex both could bind to CT DNA by intercalation mode, and double helix of DNA was damaged. Moreover, Al3+–HA complex not only displays higher absorption at therapeutic window but also displays stronger binding affinity to CT DNA than HA.Graphical abstractThe UV–vis spectra show that Al3+–Hypocrellin A complex in water solution has been synthesized. Competitive binding of HA and Al3+–HA complex for CT DNA-EB experiments suggest HA and Al3+–HA complex could bind to CT DNA and the binding constants between Al3+–HA complex and CT DNA-EB at different temperatures are larger than that of HA.Highlights► The formation of 1:1 Al3+–HA complex have been chelated in water solution. ► HA and Al3+–HA complex could bind to CT DNA by intercalation mode. ► CT DNA quench the fluorescence of HA and Al3+–HA by static process. ► The binding affinity and fraction of Al33+–HA to CT DNA are stronger than HA.

To overcome the lack of appreciable absorption in the phototherapeutic window (600–900 nm) of the naturally occurring perylenequinonoid pigment, Elsinochrome A, which limits its clinical application, an ethylenediamine-modified elsinochrome A, possessing long wavelength absorption (708 nm) was synthesized. Electron paramagnetic resonance and chemiluminescence assays indicated that ethylenediamine-modified Elsinochrome A possessed photosensitizing activity and its photodamage efficacy is greater than that of unmodified Elsinochrome A.

A new dual fluorescent probe was prepared by encapsulating the complex of cerium (III) and quinizarin into silica nanoparticles. Cerium (III) and quinizarin can form a stable dual fluorescent complex in ethanol, but this complex would dissociate in the aqueous medium, which limited its application in biosystem. So, such complex was encapsulated inside the silica nanoparticles to solve this problem. The results indicated that the stability and water solubility of the complex were greatly improved after been encapsulated into the silica nanoparticles. In addition, its dual fluorescent probe function was studied in vitro.Highlights► We studied preparation and characterization of cerium (III)/quinizarin complex. ► We embedded successfully the complexes into silica nanoparticles through an improved sol–gel method. ► The stability and water solubility of the complex were greatly improved by encapsulation. ► The result products emitted strong blue and green fluorescence in vitro. ► The nanoparticles offered potential as fluorescent nanoprobes for cell imaging.

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.

In this article, the interaction mechanism of prodigiosin (PG) with bovine hemoglobin (BHb) is studied in detail using various spectroscopic technologies. UV–vis absorption and fluorescence spectra demonstrate the interaction process. The Stern–Volmer plot and the time-resolved fluorescence study suggest the quenching mechanism of fluorescence of BHb by PG is a static quenching procedure, and the hydrophobic interactions play a major role in binding of PG to BHb. Furthermore, synchronous fluorescence studies, Fourier transform infrared (FTIR) and circular dichroism (CD) spectra reveal that the conformation of BHb is changed after conjugation with PG.Graphical abstractBar diagram of the different conformations of BHb before and after conjugation with PG.Highlights► PG can bind to BHb to form a stable complex with one binding site. ► The interaction follows the static quenching mechanism. ► The hydrophobic interactions play a major role in the binding reaction. ► The microenvironment and conformation for BHb is changed in the presence of PG. ► Some α-helix structures have been converted into the β-sheets after conjugation.

Introduction of heavy atoms around photosensitizers (PSs) generally facilitates intersystem crossing (ISC) and improves their quantum yield of singlet oxygen (1O2) generation ability, which is a key species in photodynamic therapy (PDT). Here, we report Pt(IV)- and Au(III)-modified silica nanoparticles (SN) as the drug delivery system of a hypocrellin A (HA) to improve its photodynamic activity through external heavy atom effect. Comparative studies with Pt- and Au-modified and unmodified nanoparticles have demonstrated that the intraparticle external heavy atom effect on the encapsulated HA molecules significantly enhances their efficiency of 1O2 generation and, thereby, the in vitro photodynamic efficacy to cancer cells. The results well elucidated the potential of our PSs/heavy metal ions doped nanocarrier for improving the actual efficacy of PDT.

A hydrophilic nano-scale porous ceramic material, silica nano-carrier, was prepared using microemulsion method to deliver hypocrellin A (HA), a hydrophobic photosensitive anti-cancer drug, to cancer cells in vitro. The result hypocrellin A encapsulated silica nano-carrier delivery systems (HA-SNDS) are spherical, highly monodispersed, stable in aqueous system and own high drug encapsulation ability. Irradiation of the HA-SNDS with light of suitable wavelength results in efficient generation of singlet oxygen; further more the photo-stability of HA-SNDS is superior to free HA. In aqueous medium, the fluorescence intensity of the entrapped drug is stronger than the free drug, permitting use of fluorescence mediated bioimaging studies. In addition, HA-SNDS was stable at a wide range of pH. In vitro studies have demonstrated the active uptake of HA-SNDS into the cytosol of tumor cells. Comparative studies with free HA and HA-SNDS have demonstrated that the in vitro PDT efficacy of encapsulated HA is obvious superior to free HA. All these properties of HA-SNDS could make it a promising candidate for photodynamic therapy.

An amorphous formulation of hypocrellin A for photodynamic therapy is reported which can provide stable aqueous dispersion of such hydrophobic photosensitizers. In vitro studies have demonstrated the active uptake of amorphous formulation of hypocrellin A into the mitochondria of tumor cells. Compared with Tween-80 micelle embedded hypocrellin A, low dark-toxicity but similar light-toxicity of the amorphous one to drug impregnated tumor cells was observed. Thus, the potential of using amorphous formulation of hypocrellin A as drug delivery system for photodynamic therapy has been demonstrated.We have synthesized and characterized a water-soluble hypocrellin A (HA) by making its amorphous formulation (AM-HA) with excellent water-solubility and photosensitizing properties. In vitro, AM-HA retains high light-toxicity and reduces dark-toxicity simultaneously compared to traditional delivery vehicles [Tween-80 micelle embedded hypocrellin A (TW-HA)]. These properties of AM-HA could make it a promising candidate to be used in photodynamic therapy.

The use of ceramic nano-carriers containing anti-cancer drugs for targeted delivery that span both fundamental and applied research has attracted the interest of the scientific community. In this paper, a hydrophobic photodynamic therapy drug, hypocrellin A (HA), was successfully encapsulated in water-soluble amorphous silica nanocage (HANC) by an improved sol-gel method. These nanocages are of ultrasmall size, highly monodispersed, stable in aqueous suspension, and retain the optical properties of HA. Moreover, these nanocages can be effectively delivered, subsequently taken up by cancer cells and finally targeted to mitochondria. In addition, incubation time dependent photodynamic efficacy difference between HANC and HA was investigated for the first time. Especially, the nanocages, owning extremely high stable fluorescence comparing with free HA, also have potentials as efficient probes for optical biodiagnose in vitro. All these properties of HANC could possibly make it especially promising to be used as a bimodal reagent for photodynamic therapy and biodiagnose.

A new hypocrellin A (HA) encapsulated silica nanoparticles was prepared by an improved microemulsion method based on the unique character of cetyl trimethyl ammonium bromide (CTAB). Stable aqueous dispersions of the HA-loaded nanoparticles, with the diameter about 50 nm, owned superior photo-stability and singlet oxygen generation ability to free HA. In vitro studies demonstrated the active uptake of HA-doped nanoparticles into the cytosol of HeLa (human cervix epithelioid carcinoma) cells. Significant morphology change and phototoxicity to such impregnated tumor cells was observed upon irradiation with light. Thus, the potential of using this method to prepare silica nanoparticles as drug carriers for photodynamic therapy has been demonstrated.

Photodynamic therapy (PDT) has been proved to be highly effective in the treatment of different types of cancer. A novel nano-colloid based drug carrier for PDT of elsinochrome A (EA), a hydrophobic photosensitizer, was prepared using single 3-aminopropyltriethoxysilane (APTES) which is traditionally only used as surface modification reagent. The resulting nano-colloid immobilized photosensitizers provide good water solubility and photostability. In addition, EANC preserve the key step of photogeneration of singlet oxygen, necessary for photodynamic action. Moreover, significant damage to calf thymus DNA was observed upon irradiation with light. Thus, the potential of using nano-colloid as drug carriers for photodynamic therapy has been demonstrated.

Based on theoretical predictions, water-soluble silica nanoparticle encapsulated hypocrellin A (HA) was prepared, and its photosensitization activity was evaluated. The encapsulated HA showed not only very good water solubility, but also much stronger singlet oxygen generation ability than free HA. Investigations on binding interactions with DNA showed promising results as well. These findings suggest that HA carrier can exert photodynamic action via photosensitization.

The spectrophotometric and spectrofluorimetric studies revealed that hemoglobin (Hb) could interact with hypocrellin A, a photosensitizing drug used in photodynamic therapy. It was found that this kind of interaction can induce the conformational changes in Hb. In addition, based on fluorescence quenching titration and electron paramagnetic resonance spectroscopy results, the binding parameters, thermodynamic parameters are obtained. The quenching mechanism is also proposed.

We report a facile silica nanovehicle preparation procedure for hydrophobic drug delivery, which is carried out in water without adding any surfactant and additional catalyst. This strategy includes hydrophobic drug nanopaticle preparation by reprecipitation method and in situ hydrolyzation and polymerization to encapsulate this naoparticle using only N-(β-amimoethyl)-γ-aminopropyltyiethoxysilane (AETPS). To demonstrate this technique hypocrellin A (HA), a hydrophobic photosensitizing anticancer drug, is embedded into silica nanovehicle using this simple method. The resulting HA encapsulated nanovehicles (HANV) are monodisperse and stable in aqueous solution. Comparative studies with free HA and entrapped HA have demonstrated that the encapsulation effect on the embedded photosensitizer nanoparticle significantly enhances the efficacy of singlet oxygen generation and, thereby, the in vitro photodynamic efficacy.

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.

An effective theranostic platform based on porous silica nanoparticles encapsulated with the complex of a photodynamic anticancer drug and graphene quantum dots (GQDs), with the bifunction of multicolor imaging and satisfactory photo-induced anticancer activity, was successfully designed and prepared for in vitro photodynamic therapy (PDT) of superficial cancer.