Antibody-drug conjugates (ADCs) comprised of a desirable monoclonal antibody, an active cytotoxic drug and an appropriate linker are considered to be an innovative therapeutic approach for targeted ...treatment of various types of tumors and cancers, enhancing the therapeutic parameter of the cytotoxic drug and reducing the possibility of systemic cytotoxicity. An appropriate linker between the antibody and the cytotoxic drug provides a specific bridge, and thus helps the antibody to selectively deliver the cytotoxic drug to tumor cells and accurately releases the cytotoxic drug at tumor sites. In addition to conjugation, the linkers maintain ADCs' stability during the preparation and storage stages of the ADCs and during the systemic circulation period. The design of linkers for ADCs is a challenge in terms of extracellular stability and intracellular release, and intracellular circumstances, such as the acid environment, the reducing environment and cathepsin, are considered as the catalysts to activate the triggers for initiating the cleavage of ADCs. This review discusses the linkers used in the clinical and marketing stages for ADCs and details the fracture modes of the linkers for the further development of ADCs.
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Nucleic acid aptamers have minimal immunogenicity, high chemical synthesis production, low cost and high chemical stability when compared with antibodies. However, the susceptibility to nuclease ...degradation, rapid excretion through renal filtration and insufficient binding affinity hindered their development as drug candidates for therapeutic applications. In this review, we will discuss methods to conquer these challenges and highlight recent developments of chemical modifications and technological advances that may enable early aptamers to be translated into clinical therapeutics.
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Carbon-based nanomaterials as important agents for biological applications have emerged in the past few years due to their unique optical, electronic, mechanical, and chemical properties. Many of ...these applications rely on successful surface modifications. This review article comprises two main parts. In the first part, we briefly review the properties and surface modifications of several classes of carbon nanomaterials, mainly carbon nanotubes (CNTs), graphene and its derivatives, carbon dots (CDs) and graphene quantum dots (GQDs), as well as some other forms of carbon-based nanomaterials such as fullerene, carbon nanohorns (CNHs) and carbon nanoonions (CNOs). In the second part, we focus on the biological applications of these carbon nanomaterials, in particular their applications for fluorescence biosensing as well as bioimaging.
A review of recent applications of carbon nanomaterials in fluorescence biosensing and bioimaging.
Aptamers are oligonucleotide sequences with a length of about 25–80 bases which have abilities to bind to specific target molecules that rival those of monoclonal antibodies. They are attracting ...great attention in diverse clinical translations on account of their various advantages, including prolonged storage life, little batch-to-batch differences, very low immunogenicity, and feasibility of chemical modifications for enhancing stability, prolonging the half-life in serum, and targeted delivery. In this Review, we demonstrate the emerging aptamer discovery technologies in developing advanced techniques for producing aptamers with high performance consistently and efficiently as well as requiring less cost and resources but offering a great chance of success. Further, the diverse modifications of aptamers for therapeutic applications including therapeutic agents, aptamer–drug conjugates, and targeted delivery materials are comprehensively summarized.
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IJS, KILJ, NUK, PNG, UL, UM
Exosomes are small membrane vesicles released by most eukaryotic cells. They are considered to play an essential role in cell-to-cell communication, and It is also found that they serve as functional ...mediators in many severe diseases, including progression of various types of cancers. Inhibition of exosome release may slow the progression of some cancers; thus, exosome has been an attractive target for cancer treatment. Over the years, considerable efforts have been made to discover novel, highly potent and excellently selective exosome inhibitors. Most of these inhibitors are derived from synthetic compounds, some of which are currently existed drugs and found to have the potential to inhibit exosome release. In this review, we briefly discussed the development of exosome inhibitors that are currently discovered and provided guidance for the future development of inhibitors.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Aptamers are short DNA/RNA oligonucleotides capable of binding to target molecules with high affinity and specificity. The process of selecting an aptamer is called Systematic Evolution of Ligands by ...Exponential Enrichment (SELEX). Thanks to the inherit merits, aptamers have been used in a wide range of applications, including disease diagnosis, targeted delivery agents and therapeutic uses. To date, great achievements regarding the selection, modifications and application of aptamers have been made. However, few aptamer-based products have already successfully entered into clinical and industrial use. Besides, it is still a challenge to obtain aptamers with high affinity in a more efficient way. Thus, it is important to comprehensively review the current shortage and achievement of aptamer-related technology. In this review, we first present the limitations and notable advances of aptamer selection. Then, we compare the different methods used in the kinetic characterization of aptamers. We also discuss the impetus and developments of the clinical application of aptamers.
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Drug discovery is a risky, costly and time-consuming process depending on multidisciplinary methods to create safe and effective medicines. Although considerable progress has been made by ...high-throughput screening methods in drug design, the cost of developing contemporary approved drugs did not match that in the past decade. The major reason is the late-stage clinical failures in Phases II and III because of the complicated interactions between drug-specific, human body and environmental aspects affecting the safety and efficacy of a drug. There is a growing hope that systems-level consideration may provide a new perspective to overcome such current difficulties of drug discovery and development. The systems pharmacology method emerged as a holistic approach and has attracted more and more attention recently. The applications of systems pharmacology not only provide the pharmacodynamic evaluation and target identification of drug molecules, but also give a systems-level of understanding the interaction mechanism between drugs and complex disease. Therefore, the present review is an attempt to introduce how holistic systems pharmacology that integrated in silico ADME/T (i.e., absorption, distribution, metabolism, excretion and toxicity), target fishing and network pharmacology facilitates the discovery of small molecular drugs at the system level.
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Cancer is a global health challenge. There are drawbacks to conventional chemotherapy such as poor bioavailability, development of drug resistance and severe side effects. Novel drug delivery system ...may be an alternative to optimize therapeutic effects. When such systems consist of natural materials, they offer important advantages: they are usually highly biocompatible, biodegradable, nontoxic and nonimmunogenic. Furthermore, natural materials can be easily modified for conjugation with a wide range of therapeutic agents and targeting ligands, according to the therapeutic purpose. This article reviews different natural ingredients and their applications in drug delivery systems for cancer therapy. Firstly, an overview of the polysaccharides and protein-based polymers that have been extensively investigated for drug delivery are described. Secondly, recent advances in using various natural ingredient-based polymeric nanoparticles for cancer therapy are reviewed. The characteristics of these delivery systems are summarized, followed by a discussion of future development and clinical potential. This review aims to summarize current knowledge and provide a basis for developing effective tailor-made formulations for cancer therapy in the future.
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The critical role of the gut microbiome in gastrointestinal cancers is becoming increasingly clear. Imbalances in the gut microbial community, referred to as dysbiosis, are linked to increased risks ...for various forms of gastrointestinal cancers. Pathogens like Fusobacterium and Helicobacter pylori relate to the onset of esophageal and gastric cancers, respectively, while microbes such as Porphyromonas gingivalis and Clostridium species have been associated with a higher risk of pancreatic cancer. In colorectal cancer, bacteria such as Fusobacterium nucleatum are known to stimulate the growth of tumor cells and trigger cancer-promoting pathways. On the other hand, beneficial microbes like Bifidobacteria offer a protective effect, potentially inhibiting the development of gastrointestinal cancers. The potential for therapeutic interventions that manipulate the gut microbiome is substantial, including strategies to engineer anti-tumor metabolites and employ microbiota-based treatments. Despite the progress in understanding the influence of the microbiome on gastrointestinal cancers, significant challenges remain in identifying and understanding the precise contributions of specific microbial species and their metabolic products. This knowledge is essential for leveraging the role of the gut microbiome in the development of precise diagnostics and targeted therapies for gastrointestinal cancers.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Surface functionalization of liposomes can play a key role in overcoming the current limitations of nanocarriers to treat solid tumors, i.e., biological barriers and physiological factors. The ...phospholipid vesicles (liposomes) containing anticancer agents produce fewer side effects than non-liposomal anticancer formulations, and can effectively target the solid tumors. This article reviews information about the strategies for targeting of liposomes to solid tumors along with the possible targets in cancer cells, i.e., extracellular and intracellular targets and targets in tumor microenvironment or vasculature. Targeting ligands for functionalization of liposomes with relevant surface engineering techniques have been described. Stimuli strategies for enhanced delivery of anticancer agents at requisite location using stimuli-responsive functionalized liposomes have been discussed. Recent approaches for enhanced delivery of anticancer agents at tumor site with relevant surface functionalization techniques have been reviewed. Finally, current challenges of functionalized liposomes and future perspective of smart functionalized liposomes have been discussed.
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