Carrier-free, self-assembled pure drug nanorods composed of 10-hydroxycamptothecin and chlorin e6 for combinatorial chemo-photodynamic antitumor therapy in vivo

Nanoscale. 2017 Oct 5;9(38):14347-14356. doi: 10.1039/c7nr03129g.

Abstract

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.

MeSH terms

  • A549 Cells
  • Animals
  • Camptothecin / analogs & derivatives*
  • Camptothecin / chemistry
  • Cell Line, Tumor
  • Chlorophyllides
  • Female
  • Humans
  • MCF-7 Cells
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nanotubes / chemistry*
  • Neoplasms, Experimental / drug therapy*
  • Photochemotherapy*
  • Porphyrins / chemistry*
  • Radiation-Sensitizing Agents / chemistry
  • Xenograft Model Antitumor Assays

Substances

  • Chlorophyllides
  • Porphyrins
  • Radiation-Sensitizing Agents
  • phytochlorin
  • 10-hydroxycamptothecin
  • Camptothecin