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. 2022 Dec 23;28(1):112.
doi: 10.3390/molecules28010112.

Cannabidiol as Self-Assembly Inducer for Anticancer Drug-Based Nanoparticles

Eleonora Colombo  1   2 , Davide Andrea Coppini  1   3 , Laura Polito  4 , Umberto Ciriello  5 , Giuseppe Paladino  5 , Mariafrancesca Hyeraci  6 , Maria Luisa Di Paolo  7 , Giulia Nordio  6   8 , Lisa Dalla Via  6   8 , Daniele Passarella  1
Affiliations

Cannabidiol as Self-Assembly Inducer for Anticancer Drug-Based Nanoparticles

Eleonora Colombo et al. Molecules. .

Abstract

Cannabidiol (CBD) is a biologically active compound present in the plants of the Cannabis family, used as anticonvulsant, anti-inflammatory, anti-anxiety, and more recently, anticancer drug. In this work, its use as a new self-assembly inducer in the formation of nanoparticles is validated. The target conjugates are characterized by the presence of different anticancer drugs (namely N-desacetyl thiocolchicine, podophyllotoxin, and paclitaxel) connected to CBD through a linker able to improve drug release. These nanoparticles are formed via solvent displacement method, resulting in monodisperse and stable structures having hydrodynamic diameters ranging from 160 to 400 nm. Their biological activity is evaluated on three human tumor cell lines (MSTO-211H, HT-29, and HepG2), obtaining GI50 values in the low micromolar range. Further biological assays were carried out on MSTO-211H cells for the most effective NP 8B, confirming the involvement of paclitaxel in cytotoxicity and cell death mechanism.

Keywords: anticancer drug; cannabidiol; self-assembled nanoparticles.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic structure of the drug conjugates and building blocks.
Scheme 1
Scheme 1
Retrosynthetic pathway for the conjugates 6–8a,b.
Scheme 2
Scheme 2
Synthesis of the N-desacetyl thiocolchicines-CBD conjugates 6a,b.
Scheme 3
Scheme 3
Synthesis of the podophyllotoxin-CBD conjugates 7a,b.
Scheme 4
Scheme 4
First attempts on the synthesis of paclitaxel-CBD conjugates 8a,b.
Scheme 5
Scheme 5
Synthesis of paclitaxel-CBD conjugate 8a.
Scheme 6
Scheme 6
Synthesis of paclitaxel-CBD conjugate 8b.
Figure 2
Figure 2
Self-assembly of NPs 6–8A,B from CBD-linker-drug conjugates 6–8a,b.
Figure 3
Figure 3
Effect of paclitaxel and 8B on microtubules in MSTO-211H cells. Microtubules in cells were visualized by confocal microscopy after treatment for 4h with vehicle (control, A,B), 1 μM paclitaxel (C,D) and 100 μM 8B (E,F). Cells were stained with the antibody conjugate Alexa Fluor 488 mouse anti-β-tubulin (green) and DAPI (blue) to detect microtubules and nucleus, respectively.
Figure 4
Figure 4
Flow cytometric analysis of cell death in MSTO-211H cells treated for 24 h with 12 nM paclitaxel and 1.5 μM 8B, and stained with FITC-conjugated Annexin V and PI. (A) Dot plots of a representative experiment for untreated cells (control) and cells treated with paclitaxel, or 8B. (B) Percentages of viable (Q3), apoptotic (Q2 + Q4), and necrotic (Q1) cells. Values are the mean ± SD of three independent experiments in duplicate. * p < 0.05, significant difference in comparison to the control sample.
See this image and copyright information in PMC

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