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Nanoparticle-Mediated Small RNA Deliveries for Molecular Therapies
Published in D. Sakthi Kumar, Aswathy Ravindran Girija, Bionanotechnology in Cancer, 2023
Ramasamy Paulmurugan, Uday Kumar Sukumar, Tarik F. Massoud
5-Fluoro uracil (5-FU) is a pyrimidine analog widely used as an antineoplastic cytotoxic drug in cancer therapy. 5-FU inhibits cellular thymidylate synthase to render its anticancer effect. It also has non-specific effects when delivered as a free drug. 5-FU loaded in PLGA nanoparticles, using a double emulsion method, shows better cytotoxic effects against GBM (U87MG) and breast adenocarcinoma (MCF7) cell lines compared to free drug [55]. The formulation of 5-FU in galactosylated chitosan (GC) polymer nanoparticles shows an enhanced therapeutic effect in hepatocellular carcinoma (HCC) [56, 57]. In addition, other polymers, such as hyaluronic acid–poly(ethylene glycol)–poly(lactide-co-glycolide) (HA–PEG–PLGA) and poly(γ-benzyl-L-glutamate)–poly(ethylene glycol) (PBLG–PEG), have been also evaluated for 5-FU delivery in vitro and in vivo for anticancer therapy [58, 59]. Doxorubicin (DOX) is an anthracycline antibiotic that inhibits DNA synthesis, and has been widely used anticancer chemotherapy for many cancers [45, 60]. DOX has many adverse side effects when administered as a free drug. DOX-encapsulated PLGA nanoparticles using an oil-water nanoprecipitation technique with the resulting average size of 174 nm have shown enhanced therapeutic effects in breast cancer cells compared to free drug [61]. DOX entrapped in a nanoformulation prepared from biodegradable amphiphilic diblock methoxy poly(ethylene glycol)-b-poly(ε-caprolactone-co-γ-hydroxyl-ε-caprolactone) (mPEG-b-P(CL-co-HCL)) copolymer bearing pendant hydroxyl groups showed good cytotoxicity against HepG2 cells in vitro [62]. Poloxamer 188 coated lecithin-PLGA-human serum albumin (HSA) nanoparticles loaded with DOX (DOX-L-PLGA-HSA) enabled delivery of DOX across the blood-brain barrier at therapeutically effective concentrations in vivo in rat GBM model [63]. DOX-loaded cyclo-(1,12)-PenITDGEATDSGC (cLABL) peptide conjugated PLGA nanoparticles (DOX-cLABL-PLGA NPs) show more rapid cellular uptake by A549 lung epithelial cancer cells compared to non-peptide conjugated control nanoparticles by targeting encapsulated DOX to ICAM-1 expressing cells [64]. DOX-entrapped poly(lactic-co-glycolide)-gold half-shell nanoparticles (DOX-PLGA-Au-H-S NPs) can deliver both DOX and heat simultaneously to a selected tumorigenic region when irradiated by the near-infrared (NIR) light, resulting in higher cytotoxicity and more controlled delivery into HeLa cells [65]. DOX-loaded PLGA nanoparticles show sustained drug release rate in fibroblast cells in vitro without initial burst release [66]. DOX-loaded peptide-conjugated PLGA-PEG-NH2nanoparticles containing an amino end group display three-fold higher uptake than corresponding peptide-free PLGA-PEG-NH2 nanoparticles in a human ovarian cancer SKOV3 cells with high expression of epidermal growth factor receptor (EGFR) [67].
Synthesis and in vitro anticancer properties of a novel neodymium(III) complex containing tungstogermanate and 5-fluorouracil
Published in Journal of Coordination Chemistry, 2018
Haibin Liu, Baoyang Zhou, Ce Zhao, Danfeng Zhang, Qingyin Wu, Zengqiang Li
5-Fluorouracil (5-Fu) is an antimetabolite drug which is widely applied in anticancer treatment. Owing to its excellent antineoplastic activity, 5-Fu is preferred for the treatment of cancers [11]. Although its clinical success demonstrates the excellent anticancer activity of 5-Fu, various adverse effects such as severe myelo-suppression and gastrointestinal side effects have been reported in some patients during clinical evaluation. Moreover, short half-life and poor selectivity also limit its application in anticancer treatments. For this reason, chemical modification of 5-fluorouracil becomes hot spots for researchers [12]. The rare earth elements exhibit antitumor activities through changing the cell membrane fluidity, ATP activity, permeability, intracellular and extracellular ion-exchange, cleavage the DNA/RNA chain and cell mitosis to inhibit the function of tumor cells [13, 14].
Drug delivery systems of CoFe2O4/chitosan and MnFe2O4/chitosan magnetic composites
Published in Preparative Biochemistry & Biotechnology, 2022
Ayşegül Yildirim, Yasemin Ispirli Doğaç
Within the scope of the study, these two different magnetic materials were used as drug carriers to create the synergistic effect of the magnetic hyperthermia-cancer drug. In the study, 5-Fluorouracil (5-FU), an important drug used in cancer chemotherapy in colon, rectum, breast, stomach, pancreas, bladder, cervix, head and neck, liver, ovarian, prostate, and skin cancers, was selected as a model cancer drug. It was observed that two different carrier types (CFC and MFC) prepared were able to keep the amount of active substance released in accordance with the models used for controlled drug systems.
A new Dy(III)-based metal-organic framework with polar pores for pH-controlled anticancer drug delivery and inhibiting human osteosarcoma cells
Published in Journal of Coordination Chemistry, 2019
Yong Guo, Bing Yan, Yu Cheng, Long Mu
Construction of metal-organic frameworks (MOFs) from various molecular building blocks is a flourishing research field due to their intriguing aesthetic structures and potential applications in sorption, heterogeneous catalysis, magnetism, photochemistry, and drug delivery [8–14]. MOFs have diverse structures because of the different selected metal ions, bridging modes and configurations of ligands adopted, and various reaction conditions, which allow their final properties to be finely tuned via selection of different building blocks. As compared with conventional organic and inorganic drug delivery systems, the MOF-based drug carriers display high loading capacities and the possibility of chemical functionalization, which can enhance the drug affinity. Several studies have been carried out using different drug molecules [15–19]. Among them, 5-fluorouracil (5-Fu) is very important as it is used for cancer treatment for anal, breast, colorectal, oesophageal, stomach, pancreatic, and skin cancers (especially head and neck cancers) and is well known as an anticancer drug. It is used in chemotherapy, but not extensively due to lack of a suitable carrier. Considering its small size and existence of H-bond donor and acceptor, the 5-Fu molecule might be absorbed into the pores of MOFs and realize slow release through H-bond interactions with the polar atoms on the pore surfaces of MOFs. Through careful selection of the drug carriers, the drug molecules could be released controllably. For instance, Zou et al. reported the one-pot synthesis of anticancer drugs loaded into ZIF-8 nanocarriers based on the pH-sensitivity of ZIF-8 toward the acidic microenvironment at tumor sites [18]; Yang et al. reported that ZJU-101 can release drugs based on the pH-responsive interaction between the positively charged MOF-based carrier and the negatively charged drug [19]. In this work, we synthesized a new porous Dy(III)-based MOF, [Dy(HABA)(ABA)](DMA)4] (1, H2ABA = 4,4'-azanediyldibenzoic acid, DMA = N,N-dimethylacetamide) with uncoordinated N donor sites in the porous surroundings using a bent polycarboxylic acid organic linker under solvothermal conditions. The structure of the obtained crystalline product has been determined by X-ray single-crystal diffraction, elemental analysis, TGA, XRD, and the gas sorption measurement. Due to the suitable window size and polar atom functionalized 1D channels, the activated 1 (1a) was used for anticancer drug 5-Fu loading. A moderately high drug loading and pH-dependent drug-release behavior are observed for 1a. Furthermore, as demonstrated by the MTT assay, this drug/MOF composite shows low cytotoxicity, good biocompatibility, and anticancer activity against human osteosarcoma cell lines MG63.