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

Abstract

Carrier-free nanodrugs formulated from 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, surface charge of about −33 mV. Efficient internalization of the NRs by cancer cells was observed by 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 self-assembly approach might open up new opportunities for the development of combinatorial therapeutics for tumor.

<p>Ultra-small gadolinium oxide nanocrystal sensitization of non-small-cell lung cancer cells toward X-ray irradiation by promoting cytostatic autophagy</p>

“…Studies have shown that oxidative stress produced by nanomaterials can be observed in multiple cell types. 29 The ROS can be visualized to determine the oxidative stress levels in cells with or without GONs pretreatment after X-ray irradiation using DCFH-DA as a fluorometric probe. 30 The normalized fluorescence intensities of the studied cells are shown in Figure 4C-E.…”

Multifunctional Cargo-Free Nanomedicine for Cancer Therapy

“…Chlorin e6 (Ce6) is a second-generation photosensitizer, synthesized from chlorophyll. Upon light irradiation by light in the red spectrum (655 nm), the activated Ce6 could efficiently generate 1 O 2 [ 82 ]. Moreover, there exist obvious clinical benefits achieved by the Ce6-mediated PDT on various cancer treatments, such as bladder cancer, melanoma and nasopharyngeal cancer.…”

“…Therefore, various kinds of cargo-free nanomedicines composed of Ce6 have been developed for chemo–photodynamic combination therapy. For example, Liang’s group employed a green and simple reprecipitation method to form stable carrier-free pure nanodrugs (PNDs) consisting of Ce6 and HCPT [ 82 ]. Based on their results, it has been found that the ROS-generation efficiency of Ce6 and the cytotoxicity of HCPT were not influenced during the co-self-assembly process.…”

Engineering small molecule nanodrugs to overcome barriers for cancer therapy

“…Some of them even reach up to 100%. [19][20][21] Besides, the drug loading ratio of small molecule nanodrugs is precise and tunable because of the well-defined structure of small molecules and cocktail self-assembly process. 22 And there is no concern on carrier-induced longterm toxicity for avoiding the use of additional carriers.…”