Xuefeng Ge

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.

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.

Internal heavy atom effect of Au(III) and Pt(IV) on hypocrellin A for enhanced in vitro photodynamic therapy of cancer

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.

Spectroscopic studies on the interaction of Ga3+-hypocrellin A with myoglobin

In this article, the interaction mechanism of Ga(3+)-hypocrellin A (Ga(3+)-HA) with myoglobin (Mb) is studied in detail through 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 fluorescence quenching mechanism of Mb by Ga(3+)-HA is a static quenching procedure, and the electronic transfer forces play a major role in binding Ga(3+)-HA to Mb. Furthermore, synchronous fluorescence studies and circular dichroism (CD) spectra reveal that the conformation of Mb is changed after its conjugation with Ga(3+)-HA.

Interactions of CT-DNA with Hypocrellin A and its Al3+–Hypocrellin A complex

In this study, the chelation of Hypocrellin A (HA) with Al(3+) in water solution has been synthesized, and the interactions of HA and Al(3+)-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 Al(3+)-HA complex both could bind to CT DNA by intercalation mode, and double helix of DNA was damaged. Moreover, Al(3+)-HA complex not only displays higher absorption at therapeutic window but also displays stronger binding affinity to CT DNA than HA.

Modulating the photo-exciting process of photosensitizer to improve in vitro phototoxicity by preparing its self-assembly nanostructures

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.

Comparison and investigation of bovine hemoglobin binding to dihydroartemisinin and 9-hydroxy-dihydroartemisinin: Spectroscopic characterization

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.

Complexation of Hypocrellin A with Al3+ in water solution and the photodynamic therapy study

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.

A facile drug delivery system preparation through the interaction between drug and iron ion of transferrin

Many anticancer drugs have the capability to form stable complex with metal ions. Based on such property, a simple method to combine these drugs with transferrin, through the interaction between drug and Fe ion of transferrin, to improve their anticancer activity, is proposed. To demonstrate this technique, the complex of photosensitive anticancer drug hypocrellin A and transferrin was prepared by such facile method. The results indicated that the complex of hypocrellin A and transferrin can stabilize in aqueous solution. In vitro studies have demonstrated the superior cancer cell uptake ability of hypocrellin A–transferrin complex to the free hypocrellin A. Significant damage to such drug-impregnated tumor cells was observed upon irradiation and the cancer cells killing ability of hypocrellin A–transferrin was stronger than the free hypocrellin A within a certain range of concentrations. The above results demonstrated the validity and potential of our proposed strategy to prepare the drug delivery system of this type of anti-cancer drugs and transferrin.