Carbon nanotubes for delivery of small molecule drugs Wong, Bin Sheng; Yoong, Sia Lee; Jagusiak, Anna ...
Advanced drug delivery reviews,
December 2013, 2013-Dec, 2013-12-00, 20131201, Volume:
65, Issue:
15
Journal Article
Peer reviewed
In the realm of drug delivery, carbon nanotubes (CNTs) have gained tremendous attention as promising nanocarriers, owing to their distinct characteristics, such as high surface area, enhanced ...cellular uptake and the possibility to be easily conjugated with many therapeutics, including both small molecules and biologics, displaying superior efficacy, enhanced specificity and diminished side effects. While most CNT-based drug delivery system (DDS) had been engineered to combat cancers, there are also emerging reports that employ CNTs as either the main carrier or adjunct material for the delivery of various non-anticancer drugs.
In this review, the delivery of small molecule drugs is expounded, with special attention paid to the current progress of in vitro and in vivo research involving CNT-based DDSs, before finally concluding with some consideration on inevitable complications that hamper successful disease intervention with CNTs.
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Cancer treatments, including traditional chemotherapy, have failed to cure human malignancies. The main reasons for the failure of these treatments are the inevitable drug resistance and serious side ...effects. In clinical treatment, only 5 percent of the 50 percent of cancer patients who are able to receive conventional chemotherapy survive. Because of these factors, being able to develop a drug and treatment that can target only cancer cells without affecting normal cells remains a big challenge. Since the special properties of cisplatin in the treatment of malignant tumors were accidentally discovered in the last century, metal anticancer drugs have become a research hotspot. Metal anticancer drugs have unique pharmaceutical properties, such as ruthenium metal drugs with their high selectivity, low toxicity, easy absorption by tumor tissue, excretion, and so on. In recent years, efficient and low-toxicity metal antitumor complexes have been synthesized. In this paper, the scientific literature on platinum (Pt), ruthenium (Ru), iridium (Ir), gold (Au), and other anticancer complexes was reviewed by referring to a large amount of relevant literature at home and abroad.
This review provides an overview of metal-based anticancer drugs and drug candidates. In particular, we focus on metal complexes that can be activated in the reducing environment of cancer cells, ...thus serving as prodrugs. There are many reports of Pt and Ru complexes as redox-activatable drug candidates, but other d-block elements with variable oxidation states have a similar potential to serve as prodrugs in this manner. In this context are compounds based on Fe, Co, or Cu chemistry, which are also covered. A trend in the field of medicinal inorganic chemistry has been toward molecularly targeted, metal-based drugs obtained by functionalizing complexes with biologically active ligands. Another recent activity is the use of nanomaterials for drug delivery, exploiting passive targeting of tumors with nano-sized constructs made from Au, Fe, carbon, or organic polymers. Although complexes of all of the above mentioned metals will be described, this review focuses primarily on Pt compounds, including constructs containing nanomaterials.
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This study investigates the chronic impact of two of the most widely consumed antineoplastic drugs, Ifosfamide (IF) and Cisplatin (CDDP), on the bivalve species Mytilus galloprovincialis under ...current (17 °C) and predicted warming conditions (21 °C). Accompanying the expected increase in worldwide cancer incidence, antineoplastics detection in the aquatic environment is also expected to rise. Mussels were exposed to varying concentrations of IF (10, 100, 500 ng/L) and CDDP (10, 100, 1000 ng/L) for 28 days. Biochemical analyses focused on metabolic, antioxidant and biotransformation capacities, cellular damage, and neurotoxicity. Results showed temperature-dependent variations in biochemical responses. Metabolic capacity remained stable in mussels exposed to IF, while CDDP exposure increased it at 1000 ng/L for both temperatures. Antioxidant enzyme activities were unaffected by IF, but CDDP activated them, particularly at 21 °C. Biotransformation capacity was unchanged by IF but enhanced by CDDP. Nevertheless, cellular damage occurred at CDDP concentrations above 100 ng/L, regardless of temperature. Integrated biomarker responses highlighted CDDP's greater impact, emphasizing the critical role of temperature in shaping organismal responses and underscoring the complexity of environmental stressor interactions.
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•Activation of antioxidant enzymes by cisplatin at 21 °C.•CDDP tended to increase biotransformation enzymes, contrarily to ifosfamide.•Cellular damage was observed at 1000 ng/L CDDP, regardless of temperature.•Organism's responses seem to be magnified by the warming temperature.•Organisms were more sensitive to CDDP than to IF, especially at 21 °C.
Metal nanoparticles (NPs) may have the potential to overcome problems related to conventional chemotherapy. Metal NPs reported to play a beneficial and powerful role in cancer therapy providing ...better targeting, gene silencing and drug delivery. Functionalised metal NPs with targeting ligands offer a better control of energy deposition in the tumours. Apart from therapeutic benefits, metal NPs are also used as a diagnostic tool for the imaging of cancer cells. Metal NP-based therapeutic systems not only provide simultaneous diagnostic and therapy but also allow controlled and targeted drug release which helps to revolutionise cancer treatment and management. This review addresses the advancement of metal NPs in tumour therapy with a focus on those being explained into clinical settings.
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In this letter, we report a series of five new RGD-containing cyclic peptides as potent inhibitors to αvβ3 integrin protein. We have incorporated various unnatural lipophilic amino ...acids into the cyclic RGD framework of cilengitide, which is selective for αvβ3 integrin. All the newly synthesized cyclic peptides were evaluated in vitrosolid phase binding assay and investigated for their bindingbehaviourtowards integrin subtypes. All the cyclic peptides were synthesized in excellent yield following solution-phase coupling strategy. The cyclic RGD peptides 1a-e exhibited IC50 of 9.9, 5.5, 72, 11 and 3.3 nM, respectively, towardsαvβ3 integrin protein. This finding offers further opportunities for the introduction unusual amino acids into the cyclic peptide framework of cilengitide.
Interaction of Metal Complexes with G-Quadruplex DNA Georgiades, Savvas N; Abd Karim, Nurul H; Suntharalingam, Kogularamanan ...
Angewandte Chemie (International ed.),
June 1, 2010, Volume:
49, Issue:
24
Journal Article
Peer reviewed
Guanine-rich sequences of DNA can assemble into tetrastranded structures known as G-quadruplexes. It has been suggested that these secondary DNA structures could be involved in the regulation of ...several key biological processes. In the human genome, guanine-rich sequences with the potential to form G-quadruplexes exist in the telomere as well as in promoter regions of certain oncogenes. The identification of these sequences as novel targets for the development of anticancer drugs has sparked great interest in the design of molecules that can interact with quadruplex DNA. While most reported quadruplex DNA binders are based on purely organic templates, numerous metal complexes have more recently been shown to interact effectively with this DNA secondary structure. This Review provides an overview of the important roles that metal complexes can play as quadruplex DNA binding molecules, highlighting the unique properties metals can confer to these molecules.
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•History of cisplatin motivates researcher about explanation of negative observation.•Knowledge of synthesis and purification of cisplatin are useful for medical purposes.•Knowledge ...of mechanism action and resistance may improve delivery of anticancer drugs.•Uses and side effects are useful for cancer patients to understand precautions.•Combination therapies and development strategies help to build more effective drugs.•Understanding of nanoconjugated platinum drugs help to deliver drugs more easily.
Cisplatin or (SP-4-2)-diamminedichloridoplatinum(II) is one of the most potential and widely used drugs for the treatment of various solid cancers such as testicular, ovarian, head and neck, bladder, lung, cervical cancer, melanoma, lymphomas and several others. Cisplatin exerts anticancer activity via multiple mechanisms but its most acceptable mechanism involves generation of DNA lesions by interacting with purine bases on DNA followed by activation of several signal transduction pathways which finally lead to apoptosis. However, side effects and drug resistance are the two inherent challenges of cisplatin which limit its application and effectiveness. Reduction of drug accumulation inside cancer cells, inactivation of drug by reacting with glutathione and metallothioneins and faster repairing of DNA lesions are responsible for cisplatin resistance. To minimize cisplatin side effects and resistance, combination therapies are used and have proven more effective to defect cancers. This article highlights a systematic description on cisplatin which includes a brief history, synthesis, action mechanism, resistance, uses, side effects and modulation of side effects. It also briefly describes development of platinum drugs from very small cisplatin complex to very large next generation nanocarriers conjugated platinum complexes.
Platinum-based anticancer drugs, including cisplatin, carboplatin, oxaliplatin, nedaplatin, and lobaplatin, are heavily applied in chemotherapy regimens. However, the intrinsic or acquired resistance ...severely limit the clinical application of platinum-based treatment. The underlying mechanisms are incredibly complicated. Multiple transporters participate in the active transport of platinum-based antitumor agents, and the altered expression level, localization, or activity may severely decrease the cellular platinum accumulation. Detoxification components, which are commonly increasing in resistant tumor cells, can efficiently bind to platinum agents and prevent the formation of platinum-DNA adducts, but the adducts production is the determinant step for the cytotoxicity of platinum-based antitumor agents. Even if adequate adducts have formed, tumor cells still manage to survive through increased DNA repair processes or elevated apoptosis threshold. In addition, autophagy has a profound influence on platinum resistance. This review summarizes the critical participators of platinum resistance mechanisms mentioned above and highlights the most potential therapeutic targets or predicted markers. With a deeper understanding of the underlying resistance mechanisms, new solutions would be produced to extend the clinical application of platinum-based antitumor agents largely.
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