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

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.

SUBMITTER: Colombo E

PROVIDER: S-EPMC9822096 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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

Colombo Eleonora E Coppini Davide Andrea DA Polito Laura L Ciriello Umberto U Paladino Giuseppe G Hyeraci Mariafrancesca M Di Paolo Maria Luisa ML Nordio Giulia G Dalla Via Lisa L Passarella Daniele D

Molecules (Basel, Switzerland) 20221223 1

Cannabidiol (CBD) is a biologically active compound present in the plants of the <i>Cannabis</i> 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 <i>N</i>-desacetyl thiocolchicine, podophyllotoxin, and paclitaxel) connected to CBD through a linker able ...[more]

PMID: 36615306

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Project description:Backgroundcis-Dichlorodiamineplatinum (CDDP) was one of the most common used drugs in clinic for cancer treatment. However, CDDP caused a variety of side effects. The abundant carboxyl groups on the surface of poly glutamic acid (PGA) could be modified with various kinds of targeted ligands. PGA delivery system loaded CDDP for cancer therapies possesses potential to overcome the side effects.Materials and methodsIn this study, we constructed a safe and efficient anticancer drug delivery system PGA-Asp-maleimide-cisplatin-peptide complex (PAMCP), which was loaded with CDDP and conjugated with the transferrin receptor (TFR)-targeting peptide through a maleimide functional linker. The size of PAMCP was identified by transmission electron microscopy (TEM) and dynamic light scattering (DLS). Fluorescence microscopy and flow cytometry methods were used to detect the cell targeting ability in vitro. The MTT assay was used to detect targeted toxicity in vitro. The in vivo acute toxicity was tested in Kun Ming (KM) mice. The tumor suppression activity and drug distribution was analyzed in nude mice bearing with HeLa tumor cells.ResultsThe nano-size was 110±28 nm detected with TEM and 89±18 nm detected with DLS, respectively. Fluorescence microscopy and flow cytometry methods indicated that PAMCP possessed excellent cell targeting ability in vitro. The MTT assay suggested that PAMCP was excellent for targeted toxicity. The acute in vivo toxicity study revealed that the body mass index and serum index in the PAMCP-treated group were superior to those in the CDDP-treated group (P<0.001), and no obvious differences were detected on comparing with the PBS- or PGA-Asp-maleimide-P8 (PAMP)-treated groups. PAMCP reduced the toxicity of CDDP, suppressed tumor cell growth, and achieved efficient anti-tumor effects in vivo. After PAMCP treatment, the toxicity of CDDP was reduced and tumor growth was more remarkably inhibited compared with the free CDDP treatment group (P<0.01). Much stronger (5-10 folds) fluorescence intensity in tumor tissue was detected compared with the irrelevant-peptide group for drug distribution analysis detected with the frozen section approach.ConclusionOur data highlighted that PAMCP reduced the side effects of CDDP and exhibited stronger anti-tumor effects. Therefore, PAMCP presented the potential to be a safe and effective anticancer pharmaceutical formulation for future clinical applications.

Project description:Mesoporous silica nanoparticles (MSNs) are promising solid supports for controlled anticancer drug delivery. Herein, we report biocompatible layer-by-layer (LbL) coated MSNs (LbL-MSNs) that are designed and crafted to release encapsulated anticancer drugs, e.g., doxorubicin hydrochloride (DOX), by changing the pH or by adding competitive agents. The LbL coating process comprises bis-aminated poly(glycerol methacrylate)s (BA-PGOHMAs) and cucurbit[7]uril (CB[7]), where CB[7] serves as a molecular bridge holding two different bis-aminated polymeric layers together by means of host-guest interactions. This integrated nanosystem is tuned to respond under specific acidic conditions or by adding adamantaneamine hydrochloride (AH), attributed to the competitive binding of hydronium ions or AH to CB[7] with BA-PGOHMAs. These LbL-MSN hybrids possess excellent biostability, negligible premature drug leakage at pH 7.4, and exceptional stimuli-responsive drug release performance. The pore sizes of the MSNs and bis-aminated compounds (different carbon numbers) of BA-PGOHMAs have been optimized to provide effective integrated nanosystems for the loading and release of DOX. Significantly, the operating pH for the controlled release of DOX matches the acidifying endosomal compartments of HeLa cancer cells, suggesting that these hybrid nanosystems are good candidates for autonomous anticancer drug nanocarriers actuated by intracellular pH changes without any invasive external stimuli. The successful cellular uptake and release of cargo, e.g., propidium iodide (PI), in human breast cancer cell line MDA-231 from PI-loaded LbL-MSNs have been confirmed by confocal laser scanning microscopy (CLSM), while the cytotoxicities of DOX-loaded LbL-MSNs have been quantified by the Cell Counting Kit-8 (CCK-8) viability assay against HeLa cell lines and fibroblast L929 cell lines. The uptake of DOX-loaded LbL-MSNs by macrophages can be efficiently reduced by adding biocompatible hydrophilic poly(ethylene glycol) or CB[7] without destroying the capping. In vivo tumor-growth inhibition experiments with BALB/c nude mice demonstrated a highly efficient tumor-growth inhibition rate of DOX-loaded LbL-MSNs, suggesting that the novel type of LbL-MSN materials hold great potentials in anticancer drug delivery.

Dataset Information

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

Publications

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

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