Targeted nanomedicines have significantly changed the way new therapeutics are designed to treat disease. Central to successful therapeutics is the ability to control the dynamics of protein–nanomaterial interactions to enhance the therapeutic effect of the nanomedicine. The aim of this review is to illustrate the diversity and versatility of the conjugation approaches involved in the synthesis of antibody–nanoparticle conjugates, and highlight significant new advances in the field of bioconjugation. Such nanomedicines have found utility as both advanced therapeutic agents, as well as more complex imaging contrast agents that can provide both anatomical and functional information of diseased tissue. While such conjugates show significant promise as next generation targeted nanomedicines, it is recognized that there are in fact no clinically approved targeted therapeutics on the market. This fact is reflected upon within this review, and attempts are made to draw some reasoning from the complexities associated with the bioconjugation chemistry approaches that are typically utilized. Present trends, as well as future directions of next generation targeted nanomedicines are also discussed.
Nanogels are hydrogels having size in nanoregime, which is composed of cross-linked polymer networks. The advantages of nanogels include stimuli-responsive nature, easy drug loading, and higher drug-loading capacity, physical stability, versatility in design, stability of entrapped drug, and controlled release of the anti-inflammatory, antimicrobial, protein, peptide and anticancer drugs. Stimuli-responsive nature of nanogel is of particular importance in anticancer and anti-inflammatory drug delivery, as cancer and inflammation are associated with acidic pH, heat generation, and change in ionic content. Nanogels composed of muco-adhesive polymers provide prolonged residence time and increase the ocular availability of loaded drugs. By forming suitably sized complex with proteins or by acting as artificial chaperones, they thus help to keep the proteins and enzymes in proper confirmation necessary for exerting biological activity; nanogels can increase the stability and activity of protein/peptide drugs. Better drug penetrations achieved by prolonged contact with skin contribute much in transdermal drug delivery. When it comes to cancer drug delivery, the presence of multiple interactive functional groups in nanogels different targeting agents can be conjugated for delivery of the selective drugs. This review focuses on applications of nanogels in cancer drug delivery and imaging, anti-inflammatory, anti-psoriatic, transdermal, ocular and protein/peptide drug delivery and therapy.
Integrating nanomaterials with biological entities has led to the development of diagnostic tools and biotechnology-derived therapeutic products. However, to optimise the design of these hybrid bionanomaterials, it is essential to understand how controlling the biological interactions will influence desired outcomes. Ultimately, this knowledge will allow more rapid translation from the bench to the clinic. In this paper, we developed a micellar system that was assembled using modular antibody-polymer amphiphilic materials. The amphiphilic nature was established using either polyethylene glycol (PEG) or a single-chain variable fragment (scFv) from an antibody as the hydrophile, and a thermoresponsive polymer (poly(oligoethylene glycol) methyl ether methacrylate) as the hydrophobe. By varying the ratios of these components, a series of nanoparticles with different antibody content was self-assembled, where the surface presentation of targeting ligand was carefully controlled. In vitro and in vivo
Colon cancer is one of the major causes of cancer deaths worldwide. Even after surgical resection and aggressive chemotherapy, 50% of colorectal carcinoma patients develop recurrent disease. Thus, the rationale of developing new therapeutic approaches to improve the current chemotherapeutic regimen would be highly recommended. There are reports on the effectiveness of combination chemotherapy in colon cancer and it has been practiced in clinics for long time. These approaches are associated with toxic side effects. Later, the drug delivery research had shown the potential of nanoencapsulation techniques and active targeting as an effective method to improve the effectiveness of chemotherapy with less toxicity. This current focus article provides a brief analysis of the ongoing research in the colon cancer area using the combinatorial nanomedicines and its outcome.
Under ultralow radiofrequency (RF) power, transferrin-conjugated graphene nanoparticles can thermally ablate drug- or radiation-resistant cancer cells very effectively. The results suggest that graphene-based RF hyperthermia can be an efficient method to manage drug-/radiation-resistant cancers.
Novel conjugates that incorporate strategies for increasing the therapeutic payload, such as targeted polymeric delivery vehicles, have great potential in overcoming limitations of conventional antibody therapies that often exhibit immunogenicity and limited drug loading. Click chemistry has significantly expanded the toolbox of effective strategies for developing hybrid polymer‐biomolecule conjugates, however, effective systems require orthogonality between the polymer and biomolecule chemistries to achieve efficient coupling. Here, three cycloaddition‐based strategies for antibody conjugation to polymeric carriers are explored and show that a purely radical‐based method for polymer synthesis and subsequent biomolecule attachment has a trade‐off between coupling efficiency of the antibody and the ability to synthesize polymers with controlled chemical properties. It is shown that careful consideration of both coupling chemistries as well as the potential effect of how this modulates the chemical properties of the polymer nanocarrier should be considered during the development of such systems. The strategies described offer insight into improving conjugate development for therapeutic and theranostic applications. In this system, polymerization using conventional and established reversible addition fragmentation chain transfer (RAFT) agents, followed by multiple post‐modification steps, always leads to systems with more defined chemical architectures compared to strategies that utilize alkyne‐functional RAFT agents.
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