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Photodynamic therapy (PDT) is strongly O2 dependent. Therefore, its therapeutic effects are seriously hindered in hypoxic tumors. Red blood cells are responsible for delivering O2 in the blood. In this manuscript, biomimetic red blood cells (BRBCs) were exploited using a layer-by-layer assembly method, using Fe3O4@CuO, oxyhemoglobin (OxyHb), a photosensitizer and a photo-cross linked acrylate modified hyaluronic acid (HA) gel shell. The Fe3O4@CuO core has very high OxyHb loading efficiency (the adsorption capacity of Fe3O4@CuO for OxyHb is derived to be 0.99 mg mg-1) to ensure a sufficient O2 supply. OxyHb was protected well by the HA shell in order to avoid O2 release during the delivery process in blood before arrival at the tumor tissue. The HA shell protection can be eliminated in position at the tumor to trigger O2 release through hyaluronidase (HAase) triggered HA degradation. Furthermore, Fe3O4 in the nanosystem can provide magnetic field assisted tumor targeting and magnetic resonance imaging of the tumor. Therefore, this work presents a highly efficient all-in-one biomimetic nanomedicine approach to overcome hypoxia and achieve tumor targeting theranostics.

The common existence of hypoxia within the tumor microenvironment severely restricts the efficacy of photodynamic therapy (PDT), which is attributed to the fact that the PDT process is strongly oxygen (O2) dependent. Here, a multifunctional composite (named CPCG), which combines polyethylene glycol (PEG) functionalized cerium oxide nanoparticles (CeO2) with photosensitizer chlorin e6 (Ce6) and glucose oxidase (GOx), is reported for generating O2 within the tumor microenvironment by the dual-path hydrogen peroxide (H2O2)-modulated ways to ameliorate hypoxia, thereby enhancing the PDT efficiency. This process is realized based on the dual enzyme-like activity of CeO2. The first modulated way is to transform the superoxide anion (O2˙-) into H2O2 by the superoxide dismutase-like activity of CeO2. The second modulated way is to decompose glucose into H2O2 through the catalysis of GOx. Subsequently, H2O2 generated from the above dual modulated ways can further produce O2via the catalase-like activity of CeO2. Additionally, the depletion of glucose could impede the nutrient supply to obtain starvation therapy. Both in vitro and in vivo experiments indicate that the CPCG composite could enhance the efficacy of photodynamic/starvation synergistic therapy. Therefore, this strategy offers great potential to modulate the O2 level in the tumor microenvironment for better therapeutic outcomes, and can act as a promising candidate in photodynamic/starvation synergistic therapy.

The tumor microenvironment (TME) is composed of tumor cells, blood vessels, cancer-associated fibroblasts (CAFs), tumor extracellular matrix (ECM), et al. The TME is closely related to anticancer treatment outcome. In this manuscript, a multifunctional nanomedicine (denoted as ZDCMH NP), combining multiple TME destruction strategies into one delivery system, has been designed and fabricated. In brief, zinc phthalocyanine (ZnPc, a photosensitizer), bromopentacarbonylmanganese(I) (COMn, a CO donor), and losartan (Dup, a CAF inhibitor) were coloaded inside mesoporous silica nanoparticles (MSNs). After that, a cross-linked hyaluronic acid (HA) gel shell was encapsulated onto the surface of the MSNs to form ZDCMH NPs. After arriving at the tumor tissue, the HA gel shell could be degraded by hyaluronidase (HAase) in the ECM to trigger encapsulated drug release. After light irradiation, ZnPc generated abundant reactive oxygen species (ROS), which could provide photodynamic therapy (PDT) activity and induce COMn to release CO, which could improve the enhanced permeability and retention (EPR) effect to promote ZDCMH NP accumulation in tumor tissue. The released Dup could inhibit CAF activity and downregulate the collagen fiber concentration in the TME to promote the deep penetration of ZDCMH NPs inside solid tumors. In vitro and in vivo anticancer studies have indicated that the destruction of the TME by multiple strategies is very helpful for ZnPc to obtain satisfactory PDT efficiency.

The low depth of tissue penetration by therapeutic light sources severely restricts photodynamic therapy (PDT) in treating deep-seated tumors. Using a luciferase/d-luciferin bioluminescence system to artificially create internal light sources in cells instead of external light sources is an effective means of solving the above problems. However, high-efficiency bioluminescence requires a higher concentration of luciferase in the cell, which poses a considerable challenge to the existing system of enzyme loading, delivery, activity and retention of drugs, and dramatically increases the cost of treatment. We loaded the substrate D-luciferin, and the photosensitizer hypericin into a polyethyleneimine (PEI)-modified nano-calcium phosphate (CaP) to solve this problem. Subsequently, the plasmid DNA containing the luciferase gene was loaded onto it using the high-density positive charge characteristic of PEI from the nanodrug (denoted DHDC). After the DHDC enters the tumor cell, it collapses and releases the plasmid DNA, which uses the intracellular protein synthesis system to continuously and massively express luciferase. Using endogenous ATP, Mg2+ , and O2 in cells, luciferase oxidizes d-luciferin and produces luminescence. The luminescence triggers hypericin excitation to generate ROS and kill cancer cells. This study provides a new strategy for the application of bioluminescence in PDT treatment.

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.

Hypoxia in solid tumors hinders the efficacy of photodynamic therapy (PDT). The route of generation of adenosine triphosphate (ATP) in hypoxic tumor cells comprises ineffective glycolysis processes, but ATP is crucial for rapid and uncontrolled growth and division. ATP depletion would inhibit DNA replication and glutathione (GSH) biosynthesis, which could inhibit the proliferation of cells and make them sensitive to PDT treatment. In this context, a nanoscale metal-organic framework nanoparticle consisting of Cu2+ and carboxyl-modified zinc phthalocyanine (ZnPc-(COOH)8) ({Cu8(ZnPc-(COOH)8)}n, ZPCN) was designed and prepared. In the dark cycle, ATP could remove Cu2+ from ZPCN and form a copper-ATP complex. ATP in the above complex could be destroyed by a copper-mediated Fenton reaction, which could finally induce ATP depletion to inhibit the proliferation of cells and make them sensitive to PDT treatment. In the light cycle, ZPCN could generate abundant cytotoxic reactive oxygen species to suppress tumor growth. These results demonstrated the potential applicability of the new strategy for achieving tumor treatment in hypoxic conditions by PDT.

In photodynamic therapy (PDT), the elevated glutathione (GSH) of cancer cells have two sides for treatment efficacy, activation pre-drug by removing activity suppressor part (advantages) and consumption reactive oxygen species (ROS) to confer PDT resistance (disadvantages). Preparation all-in-one system by simple method to make best use of the advantages and bypass the disadvantages still were remains a technical challenge. Herein, we report a robust PDT nanoparticle with above function based on a self-assembled pyridine modified Zinc phthalocyanine (ZnPc-DTP). The activity suppressor and active part of ZnPc-DTP were linked by disulfide bond. After targeting cancer cells, GSH can react with ZnPc-DTP nanoparticles by cutting disulfide bond to release its active part (ZnPc-SH) and oxidize GSH. In vitro and in vivo results indicated that ZnPc-SH can effective suppress tumor growth under the low antioxidant tumor microenvironment (TME).

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 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.

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.

In this manuscript, a photosensitive anti-cancer drug, hypocrellin A (HA), and TiO2 nanoparticles were co-loaded on the surface of graphene oxide (GO) as a photosensitive drug delivery system. In vitro studies have demonstrated the active uptake of the system into the mitochondrial of tumor cells. Such system has mutual sensitization mechanism to greatly improve the reactive oxygen species (ROSs) generation ability of the complex by visible light irradiation and, thereby, the strong photodynamic therapy (PDT) efficacy. Furthermore, during such PDT process, GO can be destroyed by the ROSs, which would helpful for the metabolism of this drug delivery system.

Carboxyl group modified zinc phthalocyanines (ZnPc) are classic and widely used photosensitizers (PSs) in upconversion nanoparticles (UCNPs) mediated photodynamic therapy (PDT) for tumor treatment. To improve the PDT activity of the complex system of ZnPc and UCNPs, many UCNPs with high red emission intensity were design and prepared. ZnPc-(COOH)4 tends to aggregate both in water and under physiological conditions, which can sharply decrease its PDT activity. Therefore, choosing monomeric COOH groups modified ZnPc as PSs is an alternative way to improve their activity. In this manuscript, three zinc(II) phthalocyanines, substituted with 4 (ZnPc-(COOH)4), 8 (ZnPc-(COOH)8) and 16 (ZnPc-(COOH)16) COOH groups, were synthesized. A comparison of the results indicated that ZnPc-(COOH)16 existed in its monomeric form under physiological conditions because of its large substituents. Moreover, ZnPc-(COOH)16 showed superior singlet oxygen (1O2) generation ability when compared to ZnPc-(COOH)4 and ZnPc-(COOH)8. Therefore, we chose ZnPc-(COOH)16 as PSs for absorption on the surface of the UCNPs. Then, they were encapsulated by crosslinked methacrylated hyaluronic acid (m-HA), which provides active tumor accumulation ability by binding its overexpressed receptors on the surface of cancer cells. The resulting nanoparticles can be effectively taken up by cancer cells and shows strong near-infrared (NIR) light triggered PDT in vitro.

Reactive oxygen species (ROS) generated during photodynamic therapy (PDT) can trigger autophagy. However, little research is focused on whether there is a synergistic anticancer effect with PDT if extra autophagy promoter or inhibitor is added. Here, it is found that autophagy promotion significantly enhances the PDT activity to cancer cells. Based on this preliminary result, a ROS-sensitive self-assembled dendrimer nanoparticle is exploited as a carrier to codeliver an autophagy promoter (rapamycin, Rapa) and photosensitizer (phthalocyanine, Pc) to the tumor. After entrapped by cancer cells and irradiated by light, the ROS generated in PDT process of Pc can trigger nanoparticle destruction to release Rapa, thus initiating the autophagy process and remarkably enhancing the efficacy of PDT, leading to efficient tumor suppression.

The formation and accumulation of toxic amyloid beta (Aβ) protofibrils in brain is recognized as the pathological hallmark of alzheimer’s disease (AD). Recent research indicated that photodynamic therapy (PDT) has potential to treat AD because reactive oxygen species (ROS) generated by photosensitizers (PS) could degrades Aβ protofibrils. Al3+ and Fe3+ were found at markedly high levels on and around Aβ protofibrils comparing with the normal part of brain. Based on this, a thymine modified Zn phthalocyanine (T-ZnPc), which can specific recognize and has strong affinity with Fe3+ and Al3+, was designed and synthesized. The recognize, affinity, Aβ protofibrils degradation and neuro protection process were monitored via ultraviolet absorption spectrometry (UV), fluorescence emission spectrum, transmission electron microscopy (TEM), flow cytometer and thiazolyl blue tetrazolium bromide (MTT) assay. The results revealed that such affinity effect greatly increases the molar extinction coefficient (from 1.70 × 104 to 4.67 × 104 and 3.30 × 104 after forming Fe-T-ZnPc and Al-T-ZnPc) and activates PDT activity of T-ZnPc to generate abundant ROS to degrade Aβ protofibrils (62% and 81% degradation by Al-T-ZnPc and Fe-T-ZnPc) and prevent its neurotoxicity based on the statistical differences analysis. Besides, T-ZnPc could inhibit new Aβ protofibrils formation and the chelation effect could reduce the free Fe3+ and Al3+ concentration in brain, which could be also helpful for AD treatment.

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.

Previous research indicated that graphene oxide (GO) can be used to deliver photosensitive anticancer drug, Hypocrellin A (HA), in photodynamic therapy (PDT). However, the anticancer activity of HA was obviously decreased after been loaded on GO. To solve this problem, a chemotherapy drug, 7-ethyl-10-hydroxycamptothecin (SN-38), was co-loaded on the HA loaded GO (HA/SN-38/GO) as a multimodal carrier for the synergistic combination of PDT and chemotherapy for cancer. In vitro results showed that the combination therapy exhibited a synergistic antiproliferative effect compared with PDT and chemotherapy alone. Therefore, HA/SN-38/GO delivery system has the potential to offer dual therapies for the synergistic combination of PDT and chemotherapy for the treatment of cancer.

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(NO 3 ) 3 and the photosensitizer hypocrellin A (HA) as potential dual delivery system for the combination of chemotherapy and photodynamic therapy (PDT). Ga(NO 3 ) 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 ( 1 O 2 ). 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(NO 3 ) 3 , thus showing a combined effect of both HA and Ga(NO 3 ) 3 .

The complex of Hypocrellin A with Al(3+) is prepared in water solution by a facile method. The water-solubility and stability of complexes are improved. Irradiation of Al(3+)-HA complex results in higher efficient generation of singlet oxygen ((1)O2) and photocleavage ability to CT DNA than HA. In vitro studies have illustrated that the Al(3+)-HA complex has anti-cancer 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.

A novel hybrid of graphene oxide (GO) and hypocrellin B (HB) was prepared using a simple noncovalent method. An efficient loading of HB on GO as high as 2 mg/mg was obtained. Mechanism analysis indicated that the π–π stacking interaction is the dominant driving force in the noncovalent interaction between HB and GO. Irradiation of HB and GO hybrid (HB–GO) results in efficient generation of singlet oxygen (1O2). In vitro studies have demonstrated the active uptake of HB–GO into the cytosol of tumor cells. Significant damage to such impregnated tumor cells was observed upon irradiation.

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 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.

A novel delivery system for the hydrophobic photosensitizer, hypocrellin A, has been developed that uses hypocrellin A nanoparticles prepared by a reprecipitation method. In comparison to the unmodified photosensitizer, the hypocrellin A nanoparticles not only possess superior water solubility, higher water and light stability but also display high singlet oxygen production and DNA photocleavage capability.

Water-soluble photosensitizing pharmaceutical of hypocrellin A (HA), prepared by embedding HA into porous hollow silica nanospheres, exhibited high singlet oxygen generation yield, good light stability and good thermal stability. Further, the in-vitro experiments indicated that such silica nanospheres containing HA can be efficiently taken up by HeLa cells, and light irradiation of such impregnated cells might result in significant cell death. Especially, HA cannot be released from silica nanospheres, which is beneficial to minimizing phototoxic side effects. Thus, these properties of HA-silica nanospheres could possibly make it especially promising to be used in clinical photodynamic therapy.

A novel amphiphilic zinc phthalocyanine (ZnPcLTs) has been synthesized, which possesses good amphiphilicity, and low aggregation. The generation efficiency of singlet oxygen and other active oxygen species' trapping rate studies were studied by electron spin resonance (ESR) spectroscopy. The results indicated that the photosensitizer possessed a higher active oxygen species generation efficiency than that of hematoporphyrin. The results of photodamage experiments towards calf-thymus DNA indicated that ZnPcLTs is a promising photosensitizer candidate for photodynamic therapy.

We first synthesized and characterized a monomer ruthenium complex of hypocrellin B (HB) by chelation with Ru(bpy)2Cl2 (in which bpy = 2,2′-bipyridine). It possesses the photosensitizing properties and can be applied in photodynamic therapy (PDT). The chemiluminescence assays indicated that the photodamage ability of the complex is stronger than that of HB.

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.

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.

Hypocrellin A (HA), an a natural perylene quinine photosensitizers (PSs), can chelate with heavy metal ions, including Au(III) and Pt(IV), to form a 1:2 complex, which exhibits enhanced (1)O2 generation quantum yield through the increased intersystem crossing efficiency mediated by internal heavy atom effect. Besides, the chelate process greatly improved the water solubility of HA. Comparative studies with HA and complexes have demonstrated that the heavy-atom effect on HA molecules enhances the efficiency of in vitro photodynamic (PDT) efficacy.

A novel 3-(4-methoxybenzylamino) propanoic acid substituted water-soluble zinc phthalocyanine (CNPcZn) was synthesized. The interaction between CNPcZn with calf thymus DNA (CT DNA) was studied using spectroscopic methods. The studies indicated that CNPcZn has strong affinity to CT DNA, and furthermore, CNZnPc showed excellent photodamaging activity to CT DNA. Above results indicated that such CNPcZn has great potential to be used as an effective photosensitizer in the field of photodynamic therapy.

Introduction of heavy atoms around photosensitizers (PSs) generally facilitates intersystem crossing (ISC) and improves their quantum yield of singlet oxygen ((1)O(2)) 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 (1)O(2) 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.

Nanoparticles of a hydrophobic photosensitizer, tetrakis (3-trifluoromethylphenoxy) zinc phthalocyanine (FPcZn) have been synthesized by using a simple reprecipitation technique. The resulting drug nanoparticles (FPcZn-NP) were spherical, highly monodispersed and stable in aqueous system, without an additional stabilizer. Comparative studies with FPcZn-NP and FPcZn indicated that after the formation of nanoparticles, FPcZn-NP maintained the efficiency of (1)O(2) generation. Further more, the in vitro studies demonstrated that such nanoparticles can be efficiently taken up by Hela cells, which might be resulted to cell death by light irradiation. These properties could make the FPcZn-NP to be a promising candidate in clinical photodynamic therapy.

Graphene oxide (GO) was investigated as a potential drug-delivery system due to its special properties and biocompatibility. Thus far, little has been done to use GO as a photosensitive drug-delivery system and to explore its anticancer activity in vitro in photodynamic therapy applications. Here, a novel GO-hypocrellin A (GO-HA) hybrid was prepared by a simple noncovalent method and its photodynamic activity was studied for the first time. The results showed that an efficient loading amount of HA on GO was as high as 1.0 mg mg(-1) and the stability of the hybrid was superior to that of the free hypocrellin A in aqueous solution. Furthermore, GO-HA can be excited by irradiation with light of appropriate wavelength to generate singlet oxygen, and in vitro experiments illustrated that GO-HA was efficiently taken up by tumor cells, and that light irradiation of such impregnated cells resulted in significant cell death. Thus, these properties of GO-HA could possibly make it especially promising for use in clinical 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.

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.