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 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.
Antimicrobial resistant Klebsiellapneumoniae (K. pneumoniae), as being a pathogen of critical clinical concern, urgently demands effective therapeutic options. However, the discovery of novel antibiotics over the last three decades has declined drastically and necessitates exploring novel strategies. Metabolomic modulation has been the promising approach for the development of effective therapeutics to deal with AMR; however, only limited efforts have been made to-date, possibly due to the unavailability of suitable metabolites extraction protocols. Therefore, in order to establish a detailed metabolome of K. pneumoniae and identify a method for targeted exploration of metabolites that are involved in the regulation of AMR associated processes, metabolites were extracted using multiple methods of metabolites extraction (freeze–thaw cycle (FTC) and sonication cycle (SC) method alone or in combination (FTC followed by SC; FTC + SC)) from K. pneumoniae cells and then identified using an orbitrap mass analyzer (ESI-LC–MS/MS). A total of 151 metabolites were identified by using FTC, 132 metabolites by using FTC+SC, 103 metabolites by using SC and 69 metabolites common among all the methods used which altogether enabled the identification of 199 unique metabolites. Of these 199, 70 metabolites were known to have an association with AMR phenotype and among these, the FTC + SC method yielded better (identified 55 metabolites), quantitatively and qualitatively compared to FTC and SC alone (identified 51 and 41 metabolites respectively). Each method of metabolite extraction showed a definite degree of biasness and specificity towards chemical classes of metabolites and jointly contributed to the development of a detailed metabolome of the pathogen. FTC method was observed to give higher metabolomic coverage as compared to SC alone and FTC + SC. However, FTC + SC resulted in the identification of a higher number of AMR associated metabolites of K. pneumoniae compared to FTC and SC alone.
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