Jiahong Zhou

Graphene Oxide Noncovalent Photosensitizer and Its Anticancer Activity In Vitro

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.

Combination of chemotherapy and photodynamic therapy using graphene oxide as drug delivery system

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.

Spectroscopic studies on the interaction of hypocrellin A and hemoglobin

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.

A new sol-gel silica nanovehicle preparation for photodynamic therapy in vitro

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-(beta-amimoethyl)-gamma-aminopropyltriethoxysilane (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.

Synthesis of novel octa-cationic and non-ionic 1,2-ethanediamine substituted zinc (II) phthalocyanines and their in vitro anti-cancer activity comparison

Novel tetra-substituted zinc phthalocyanines (Pcs) bearing 1,2-ethanediamine group and the quaternized derivatives were synthesized and characterized. The photophysical and cellular properties of these Pcs were investigated. The results indicated that the quaternized ionic effect can greatly improve the water-solubility of Pcs and reduce their aggregation degree in aqueous solution. Comparative studies with quaternized phthalocyanine and its unquaternized counterpart have also demonstrated that the quaternary action on the molecules significantly enhances the fluorescence quantum yields, fluorescence lifetimes, efficiency of singlet oxygen production and, thereby, the in vitro photodynamic therapy efficacy.

External heavy-atomic construction of photosensitizer nanoparticles for enhanced in vitro photodynamic therapy of cancer.

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.

A multi-spectroscopic approach to investigate the interaction of prodigiosin with ct-DNA

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 4.46×10(4) and 2.32×10(4)M(-1) at 298 and 310K, respectively, and the corresponding thermodynamic parameters ΔG, ΔH, ΔS at various temperatures were obtained.

Mitochondria-targeting photosensitizer-encapsulated amorphous nanocage as a bimodal reagent for drug delivery and biodiagnose in vitro

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.

Study on the conformation changes of Lysozyme induced by Hypocrellin A: The mechanism investigation

The interactions between Lysozyme and Hypocrellin A are investigated in details using time-resolved fluorescence, fourier transform infrared spectroscopy (FTIR), circular dichroism spectroscopy (CD), three-dimensional fluorescence spectra, and thermal gravimetric analysis (TGA) techniques. The results of time-resolved fluorescence suggest that the quenching mechanism is static quenching. FTIR and CD spectroscopy provide evidences of the reducing of α-helix after interaction. Hypocrellin A could change the micro-environmental of Lysozyme according to hydrophobic interaction between the aromatic ring and the hydrophobic amino acid residues, and the altered polypeptide backbone structures induce the reduction of α-helical structures. Moreover, TGA study further demonstrates the structure changes of Lysozyme on the effect of Hypocrellin A. This study could provide some important information for the derivatives of HA in pharmacy, pharmacology and biochemistry.

Studies on the binding behavior of prodigiosin with bovine hemoglobin by multi-spectroscopic techniques.

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.