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Theranostics: A New Holistic Approach in Nanomedicine
Published in D. Sakthi Kumar, Aswathy Ravindran Girija, Bionanotechnology in Cancer, 2023
Ankit Rochani, Sreejith Raveendran
Studies discussed in this chapter show the importance of polymer-encapsulated, conjugated, surface-coated, and composite nanosystems for the treatment and diagnosis of chronic conditions like cancer. These designs have been adopted with the fundamental attempt of combining the knowledge of various bioimaging techniques (PL, MRI, FRET, ultrasound, PET, PET-CT, and others) along with therapeutic (hyperthermia, chemotherapy, radiotherapy, photodynamic, and others) potential of organic or metallic particles for theranostic applications. Novel nanodesigns, like a rtificial molecular machines or nanorobots that work on the energy supplied by simple catalytic reactions [148], are still under development, and very little is known about their functioning as well as their application in nanomedicine or theranostics. Given the success of fundamental NPs, theranostic nanosystems will provide the relatively better real-time option of imaging-guided tactical therapeutic options to reduce the unnecessary side effects caused due to classical therapies.
Emerging National and Global Nanomedicine Initiatives
Published in Harry F. Tibbals, Medical Nanotechnology and Nanomedicine, 2017
Under the leadership of the NIH, nanoscience is being developed in conjunction with advanced medical science for further precision in diagnosis and treatment. Multidisciplinary biomedical scientific teams including biologists, physicians, mathematicians, engineers, and computer scientists are working to gather information about the physical properties of intracellular structures upon which biology’s molecular machines are built. New emphasis is being given to moving medical science from the laboratory to the bedside and the community.
Energy Demand of Muscle Machines
Published in Peter W. Hochachka, Muscles as Molecular and Metabolic Machines, 2019
If this model of muscle contraction (which assumes that the power stroke is produced by a large scale structural change/swinging motion of the myosin head and that one stroke cycle corresponds to one ATPase catalytic cycle) were complete and generally applicable, at the monomolecular level it would require force fluctuations during the ATPase and power stroke cycles, with zero force in the “off” position (Figure 4–3). However, recent nano-manipulation studies of actomyosin motors in vitro—involving single-motor force recording comparable to single channel recording in membrane studies—find that 1:1 coupling between chemical and mechanical reactions and thus predicted large scale fluctuations in force over the ATPase and power stroke cycles appear to hold only at high work loads. At intermediate and low work loads, the actomyosin motor produces an almost constant force during the ATPase cycle. This indicates that the actomyosin motor at submaximal work loads can perform multiple power strokes during the ATPase cycle; i.e., the coupling between the ATPase and power stroke cycles is variable, depending on the load (Figure 4–4). If the free energy of ATP hydrolysis is fractionated into smaller packets available for several power strokes, the energy for each power stroke will necessarily be several times smaller than for the single overall ATPase reaction. How this is achieved is not understood at this time. Nevertheless, these new studies (Yanagida et al., 1993) emphasize that actomyosin is an exquisite molecular machine that can operate at high efficiency (up to and exceeding 40%), even when the input energy is close to the average thermal energy, in contrast to manmade machines, which operate at energy levels much higher than thermal noise. These exquisite functions of the actomyosin motor, at once a catalyst and a mechanical rächet, in the intact sarcomere are not possible without Ca++.
Schistosome proteomics: updates and clinical implications
Published in Expert Review of Proteomics, 2022
William Castro-Borges, R Alan Wilson
The first schistosome study used a 2D gel-based approach to compare the soluble proteome of four parasitic stages (cercariae, lung schistosomula, adult worms, and eggs) corresponding to preparations (SCAP, SLAP, SWAP, and SEA, respectively) frequently used in immunostimulatory assays up to the present day [2]. With large 2D gels (18 cm) and wide pH range first dimension IPG strip (3–10), such gels would maximally accommodate 25% of the S. mansoni proteome; inevitably the most abundant spots were constituents of internal tissues such as muscle and parenchyma (actin, glycolytic enzymes, and chaperones). Essentially, this analysis of schistosome homogenates tells you what the host will encounter when a parasite dies so is of little use to define the interface between live worms and the host. Gel spots can of course be quantified before mass spectrometry, giving an independent estimate of protein abundance. Large 2D gel separations have also been applied to identify constituents of some solubilized parasite fractions but have less utility in this respect than LC-MS/MS [18]. However, they have proved useful in the characterization of isolated molecular machines, specifically the 20S proteasome [19]. Over 50 alpha and beta subunits of the purified complex from adult schistosomes were identified, revealing the existence of isoforms for the canonical set of 28 polypeptides comprising this nanomachine. More recently, it was shown that this conserved proteolytic complex is potentially druggable to combat schistosomes, with particular compounds exhibiting differential inhibition of its protease activities compared to those observed in mammalian cell lines [20].
Seek and destroy: improving PK/PD profiles of anticancer agents with nanoparticles
Published in Expert Review of Clinical Pharmacology, 2018
Anne Rodallec, Raphaelle Fanciullino, Bruno Lacarelle, Joseph Ciccolini
Nanobots are tiny molecular machines expected to be the next smart vehicles to be developed. Rather than interfering with standard pharmacological targets, nanobots are supposed to trigger cell death through mechanical effects, e.g. by drilling holes into cancer cell membranes. Although only at the very early stages of development, such new entities will probably play a major role in fight cancer disease in the future. Because no drugs will be carried out anymore, a brand new way to think about the PK/PD relationships will have to be invented.