Strategies for the production of long-acting therapeutics and efficient drug delivery for cancer treatment

Al-Qahtani, Alanod; O’Connor, David; Dömling, Alexander; Goda, Sayed K.

doi:10.1016/j.biopha.2019.108750

Cited by 85 publications

(55 citation statements)

References 104 publications

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“…28 For example, it's known to increase the in vivo halflife of parenteral drugs as well as reduce immunogenicity. [28][29][30] In this work, we study the effects of MDPs with and without PEGylation on model lipid membranes using SAXS/SANS and specular neutron reectometry (NR) at solid-liquid interfaces. NR is a powerful tool for studying peptide-membrane interactions due to the ability to resolve the detailed structure of membranes on length scales from a fewÅngstrøms to tens of nanometres.…”

Section: Introductionmentioning

confidence: 99%

Lipid membrane interactions of self-assembling antimicrobial nanofibers: effect of PEGylation

et al. 2020

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Section: Introductionmentioning

confidence: 99%

Lipid membrane interactions of self-assembling antimicrobial nanofibers: effect of PEGylation

et al. 2020

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“…PEGylation is an established technology used to increase serum half-life extension for many small molecular-sized protein therapeutics by increasing their hydrodynamic size and radius, to increase resistance to proteases and potentially limit the generation of an immune response. 30,31 In addition, PEG is a polyether, making it very hydrophilic. We postulate that these properties incorporated into a branched chain linker are important to overcome the fast serum clearance of an antibody highly conjugated with the highly hydrophobic IR800 dye.…”

Section: Summary and Discussionmentioning

confidence: 99%

Improved antibody-guided surgery with a near-infrared dye on a PEGylated linker for CEA-positive tumors

et al. 2019

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Real-time intraoperative image-guided cancer surgery promises to improve oncologic outcomes. Tumor-specific antibodies conjugated with near-infrared (NIR) fluorophores have demonstrated the potential to enhance visualization of solid tumor margins and metastatic disease; however, multiple challenges remain, including improvement in probe development for clinical utility. We have developed an NIR-IR800 dye on a PEGylated linker (sidewinder) conjugated to the humanized anti-carcinoembryonic antigen (CEA) antibody (M5A) with extended in vivo serum and tumor persistence. The anti-CEA M5A-sidewinder has a high dyeto-antibody ratio (average of 7 per antibody) that allows, in an orthotopic implanted human pancreatic cancer mouse model increased tumor fluorescence, higher tumor-to-background ratio and extends the surgical scheduling window compared to current antibody dye conjugates. These preclinical results demonstrate the potential of this probe for fluorescence-guided surgery of CEA-positive gastrointestinal cancers.

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“…To increase the circulation time and to overcome the renal filtration, aptamers are generally modified with large groups such as PEG, cholesterol, proteins, and liposomes. PEG is most commonly used and approved by FDA for prolong circulation and half-life; this improves the in vivo bioavailability of therapeutics aptamers [ 116 ]. The FDA approved drug, Macugen increased the half-life from 9.3 to 12 hours in plasma, after intravenous or subcutaneous injection, respectively, after PEG modification.…”

Section: Challengesmentioning

confidence: 99%

Current Perspectives on Aptamers as Diagnostic Tools and Therapeutic Agents

2020

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Aptamers are synthetic single-stranded DNA or RNA sequences selected from combinatorial oligonucleotide libraries through the well-known in vitro selection and iteration process, SELEX. The last three decades have witnessed a sudden boom in aptamer research, owing to their unique characteristics, like high specificity and binding affinity, low immunogenicity and toxicity, and ease in synthesis with negligible batch-to-batch variation. Aptamers can specifically bind to the targets ranging from small molecules to complex structures, making them suitable for a myriad of diagnostic and therapeutic applications. In analytical scenarios, aptamers are used as molecular probes instead of antibodies. They have the potential in the detection of biomarkers, microorganisms, viral agents, environmental pollutants, or pathogens. For therapeutic purposes, aptamers can be further engineered with chemical stabilization and modification techniques, thus expanding their serum half-life and shelf life. A vast number of antagonistic aptamers or aptamer-based conjugates have been discovered so far through the in vitro selection procedure. However, the aptamers face several challenges for its successful clinical translation, and only particular aptamers have reached the marketplace so far. Aptamer research is still in a growing stage, and a deeper understanding of nucleic acid chemistry, target interaction, tissue distribution, and pharmacokinetics is required. In this review, we discussed aptamers in the current diagnostics and theranostics applications, while addressing the challenges associated with them. The report also sheds light on the implementation of aptamer conjugates for diagnostic purposes and, finally, the therapeutic aptamers under clinical investigation, challenges therein, and their future directions.

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Strategies for the production of long-acting therapeutics and efficient drug delivery for cancer treatment

Cited by 85 publications

References 104 publications

Lipid membrane interactions of self-assembling antimicrobial nanofibers: effect of PEGylation

Lipid membrane interactions of self-assembling antimicrobial nanofibers: effect of PEGylation

Improved antibody-guided surgery with a near-infrared dye on a PEGylated linker for CEA-positive tumors

Current Perspectives on Aptamers as Diagnostic Tools and Therapeutic Agents

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