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Efficiency of newly formulated camptothecin with ?-cyclodextrin-EDTA-Fe₃O₄ nanoparticle-conjugated nanocarriers as an anti-colon cancer (HT29) drug.

ABSTRACT: Camptothecin (CPT) is an anti-cancer drug that effectively treats various cancers, including colon cancer. However, poor solubility and other drawbacks have restricted its chemotherapeutic potential. To overcome these restrictions, CPT was encapsulated in CEF (cyclodextrin-EDTA-FE₃O₄), a composite nanoparticle of magnetic iron oxide (Fe₃O₄), and ?-cyclodextrin was cross-linked with ethylenediaminetetraacetic acid (EDTA). This formulation improved CPT's solubility and bioavailability for cancer cells. The use of magnetically responsive anti-cancer formulation is highly advantageous in cancer chemotherapy. The chemical characterisation of CPT-CEF was studied here. The ability of this nano-compound to induce apoptosis in HT29 colon cancer cells and A549 lung cancer cells was evaluated. The dose-dependent cytotoxicity of CPT-CEF was shown using MTT. Propidium iodide and Annexin V staining, mitochondrial membrane depolarisation (JC-1 dye), and caspase-3 activity were assayed to detect apoptosis in CPT-CEF-treated cancer cells. Cell cycle analysis also showed G1 phase arrest, which indicated possible synergistic effects of the nano-carrier. These study results show that CPT-CEF causes a dose-dependent cell viability reduction in HT29 and A549 cells and induces apoptosis in colon cancer cells via caspase-3 activation. These data strongly suggest that CPT could be used as a major nanocarrier for CPT to effectively treat colon cancer.

SUBMITTER: Krishnan P

PROVIDER: S-EPMC5591276 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Efficiency of newly formulated camptothecin with β-cyclodextrin-EDTA-Fe3O4 nanoparticle-conjugated nanocarriers as an anti-colon cancer (HT29) drug.

Krishnan Poorani P Rajan Mariappan M Kumari Sharmilah S Sakinah S S Priya Sivan Padma SP Amira Fatin F Danjuma Lawal L Pooi Ling Mok M Fakurazi Sharida S Arulselvan Palanisamy P Higuchi Akon A Arumugam Ramitha R Alarfaj Abdullah A AA Munusamy Murugan A MA Hamat Rukman Awang RA Benelli Giovanni G Murugan Kadarkarai K Kumar S Suresh SS

Scientific reports 20170908 1

Camptothecin (CPT) is an anti-cancer drug that effectively treats various cancers, including colon cancer. However, poor solubility and other drawbacks have restricted its chemotherapeutic potential. To overcome these restrictions, CPT was encapsulated in CEF (cyclodextrin-EDTA-FE3O4), a composite nanoparticle of magnetic iron oxide (Fe3O4), and β-cyclodextrin was cross-linked with ethylenediaminetetraacetic acid (EDTA). This formulation improved CPT's ...[more]

PMID: 28887536

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Project description:The design and study of efficient polymer-based drug delivery systems for the controlled release of anticancer drugs is one of the pillars of nanomedicine. The fight against metastatic and invasive cancers demands therapeutic candidates with increased and selective toxicity towards malignant cells, long-term activity and reduced side effects. In this sense, polyphosphazene nanocarriers were synthesized for the sustained release of the anticancer drugs camptothecin (CPT) and epirubicin (EPI). Linear poly(dichloro)phosphazene was modified with lipophilic tocopherol or testosterone glycinate, with antioxidant and antitumor activity, and with hydrophilic Jeffamine M1000 to obtain different polyphosphazene nanocarriers. It allowed us to encapsulate the lipophilic CPT and the more hydrophilic EPI. The encapsulation process was carried out via solvent exchange/precipitation, attaining a 9.2-13.6 wt% of CPT and 0.3-2.4 wt% of EPI. CPT-loaded polyphosphazenes formed 140-200 nm aggregates in simulated body physiological conditions (PBS, pH 7.4), resulting in an 80-100-fold increase of CPT solubility. EPI-loaded polyphosphazenes formed 250 nm aggregates in an aqueous medium. CPT and EPI release (PBS, pH 7.4, 37 °C) was monitored for 202 h, being almost linear during the first 8 h. The slow release of testosterone and tocopherol was also sustained for 150 h in PBS (pH 7.4 and 6.0) at 37 °C. The co-delivery of testosterone or tocopherol and the anticancer drugs from the nanocarriers was expected. Cells of the human breast cancer cell line MCF-7 demonstrated good uptake of anticancer-drug-loaded nanocarriers after 6 h. Similarly, MCF-7 spheroids showed good uptake of the anticancer-drug-loaded aggregates after 72 h. Almost all anticancer-drug-loaded polyphosphazenes exhibited similar or superior toxicity against MCF-7 cells and spheroids when compared to raw anticancer drugs. Additionally, cell-cycle arrest in the G2/M phase was increased in response to the drug-loaded nanocarriers. Almost no toxicity of anticancer-drug-loaded aggregates against primary human lung fibroblasts was observed. Furthermore, the aggregates displayed no hemolytic activity, which is in contrast to the parent anticancer drugs. Consequently, synthesized polyphosphazene-based nanocarriers might be potential nanomedicines for chemotherapy.

Dataset Information

Efficiency of newly formulated camptothecin with ?-cyclodextrin-EDTA-Fe₃O₄ nanoparticle-conjugated nanocarriers as an anti-colon cancer (HT29) drug.

Publications

Efficiency of newly formulated camptothecin with β-cyclodextrin-EDTA-Fe<sub>3</sub>O<sub>4</sub> nanoparticle-conjugated nanocarriers as an anti-colon cancer (HT29) drug.

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Efficiency of newly formulated camptothecin with ?-cyclodextrin-EDTA-Fe3O4 nanoparticle-conjugated nanocarriers as an anti-colon cancer (HT29) drug.

Publications

Efficiency of newly formulated camptothecin with β-cyclodextrin-EDTA-Fe<sub>3</sub>O<sub>4</sub> nanoparticle-conjugated nanocarriers as an anti-colon cancer (HT29) drug.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Efficiency of newly formulated camptothecin with ?-cyclodextrin-EDTA-Fe₃O₄ nanoparticle-conjugated nanocarriers as an anti-colon cancer (HT29) drug.