phytochlorin and 10-hydroxycamptothecin

The combination of chemo-photodynamic therapy based on nano-technology has emerged as a preferable and promising measure for synergetic antitumor therapy.. The aim of this study was expected to overcome most of the safety concerns from nano-carriers and improve the chemo-photodynamic synergistic antitumor efficacy.. Herein, we reported a facile and effective approach based on the self-assembly of chemotherapeutic agent 10-hydroxycamptothecin (HCPT) and photosensitizer chlorin e6 (Ce6) for preparing stably dual-functional nanorods (NRs).. The chemical thermodynamic parameters obtained from isothermal titration calorimeter (ITC) and the microcosmic configuration snapshots acquired by molecular dynamics (MD) simulations verified that HCPT and Ce6 molecules tended to assemble with each other through various intermolecular forces. The as-prepared HCPT/Ce6 NRs possessed a relatively uniform size of around 165 nm and zeta potential of about -29 mV, together with good stability in aqueous solution and freeze-dried state. In addition, both the extra- and intracellular reactive oxygen species (ROS) generation capacity of the NRs under laser irradiation was significantly enhanced compared with Ce6 injections. Moreover, the dual-functional HCPT/Ce6 NRs exhibited a substantial in vitro/in vivo synergistic antitumor efficacy under laser irradiation due to the integration of the two therapeutic modalities into one drug delivery system. Besides, no obvious hepatic or renal toxicity was observed in the NRs treatment groups.. Taken together, HCPT/Ce6 NRs demonstrated a powerful efficacy in chemo-photodynamic therapy for breast cancer. Therefore, the carrier-free dual-functional NRs prepared in a facile and effective strategy might give inspiration for the development of combined antitumor therapy.

Topics: Animals; Antineoplastic Agents; Camptothecin; Cell Line, Tumor; Chlorophyllides; Drug Delivery Systems; Drug Liberation; Drug Stability; Drug Synergism; Female; Mice, Inbred BALB C; Molecular Dynamics Simulation; Nanotubes; Photochemotherapy; Photosensitizing Agents; Porphyrins; Reactive Oxygen Species

Carrier-free nanodrugs formulated from the supramolecular self-assembly of pure drug molecules have emerged as an innovative and promising strategy for tumor therapy. We report herein a new and simple method to directly assemble a small hydrophobic anticancer drug, 10-hydroxycamptothecin (HCPT), with a photosensitizer chlorin e6 (Ce6) to form stable, discrete nanorods (NRs), which not only circumvent the extreme hydrophobicity of HCPT but also incorporate two different modalities into one delivery system for combination therapy. Different ratios of HCPT to Ce6 were evaluated to afford the optimal nanoformulation. The as-prepared HCPT/Ce6 NRs were fully characterized, indicating a relatively uniform size of about 360 nm in length and 135 nm in width, and a surface charge of about -33 mV. Efficient internalization of the NRs by cancer cells was observed by using a confocal microscope and the generation of singlet oxygen species arising from the NRs under 655 nm laser irradiation was detected by DCFH-DA. As a result, very potent in vitro efficacy against several kinds of cancer cell lines was achieved through chemo-photodynamic dual therapy. The in vivo tumor suppression effect of HCPT/Ce6 NRs was verified on a subcutaneous xenograft mouse model, achieving almost complete inhibition of the tumor growth, which may benefit from the superiority of nanomedicine and combination therapy. The rationale of this facile and green strategy for carrier-free nanodrug formulation via the self-assembly approach might provide new opportunities for the development of combinatorial therapeutics for tumors.

Topics: A549 Cells; Animals; Camptothecin; Cell Line, Tumor; Chlorophyllides; Female; Humans; MCF-7 Cells; Mice; Mice, Inbred BALB C; Mice, Nude; Nanotubes; Neoplasms, Experimental; Photochemotherapy; Porphyrins; Radiation-Sensitizing Agents; Xenograft Model Antitumor Assays