We show an experimental approach for directly observing the condensation of polynucleotides and their electrolyte counterions at a liquid/solid interface. X-ray standing waves (XSW) generated by Bragg diffraction from a d = 20 nm Si/Mo multilayer substrate are used to measure the distinct distribution profiles of the polyanions and simple cations along the surface normal direction with subnanometer resolution. The 1D spatial sensitivity of this approach is enhanced by observing the XSW induced fluorescence modulations over multiple orders of Bragg peaks. We study the interesting divalent cation driven adsorption of anionic polynucleotides to anionic surfaces by exposing a hydroxyl-terminated silica surface to an aqueous solution with ZnCl2 and mercurated poly-uridylic acid (a synthetic RNA molecule). The in situ long-period XSW measurements are used to follow the evolution of both the Zn and Hg distribution profiles during the adsorption process. The conditions and physical mechanisms that govern the observed divalent cation adsorption and subsequent polynucleotide adsorption to an anionic surface are explained by a thermodynamic model that incorporates nonlinear electrostatic effects.
Stimuli-triggered drug delivery systems hold vast promise in local infection treatment for the site-specific targeting and shuttling of drugs. Herein, chitosan conjugates (SPCS) installed with sialic acid (SA) and phenylboronic acid (PBA) were synthesized, of which SA served as targeting ligand for coccidium and reversible-binding bridge for PBA. The enhanced drug-loading capacity of SPCS micelles was attributed to a combination assembly from hydrophobicity-driving and reversible borate bridges. The drug-loaded SPCS micelles shared superior biostability in upper gastrointestinal tract. After reaching the lesions, the borate bridges were snipped by carbohydrates under a higher pH followed by accelerated drug release, while SA exposure on micellar surface facilitated drug cellular internalization to eliminate parasites inside. The drug-micelles revealed an enhanced anti-coccidial capacity with a higher index of 185.72 compared with commercial preparation. The dual-responsive combination of physicochemical assembly could provide an efficient strategy for the exploitation of stable, safe and flexible anti-infectious drug delivery systems.
A series of novel azo polyelectrolytes have been synthesized based on an extremely reactive precursor polymer, poly(acryloyl chloride) (PAC), prepared from acryloyl chloride by radical polymerization. The precursor polymer was post-functionalized by the Schotten-Baumann reaction of PAC and several aromatic azo reactants containing hydroxyl end groups. The degrees of functionalization were controlled by selecting suitable feed ratios between the azo reactants and poly(acryloyl chloride) and the unreacted acyl chloride groups were hydrolyzed to obtain ionizable carboxyl groups. The products were characterized by elemental analysis, FT-IR, 1H NMR and UV−vis spectroscopy. Irradiated by 365 nm UV light, azo polyelectrolytes PPAPE, PEAPE and PCAPE showed a significant photochromic effect. The contact angles of water on the surfaces of spin-coated films of PPAPE and PEAPE decreased evidently upon UV irradiation. The extent of the photoinduced contact angle changes depends on the type of the azo chromophores and the degree of functionalization. Self-assembled multilayers of the azo polyelectrolytes were fabricated by a layer-by-layer adsorption method. A significant photochromic effect from cis−trans isomerization of the azo chromophores was observed for the multilayers. The photoinduced contact angle changes of water on the self-assembled multilayers were also observed.
Icaritin is an active ingredient in Epimedium, which has a variety of pharmacological activities. However, the low activity of Icaritin and the unclear target greatly limit its application. Therefore, based on the structure of Icaritin, we adopted the strategy of replacing toxic groups and introducing active groups to design and synthesize a series of new analogues. The top compound C3 exhibited better antimultiple myeloma activity with an IC50 of 1.09 μM for RPMI 8226 cells, induced RPMI 8226 apoptosis, and blocked the cell cycle in the S phase. Importantly, transcriptome analysis, cellular thermal shift assay, and microscale thermophoresis assay confirmed that DEPTOR was the target of C3. Moreover, we explored its binding mode with C3. Especially, C3 displayed satisfactory inhibition of tumor growth in RPMI 8226 xenografts without obvious side effects. In summary, C3 was discovered as a novel putative inhibitor of DEPTOR for the treatment of multiple myeloma.
Coccidiosis is a widespread and economic disease that deteriorates the growth of infected animals and largely affects our food safety. It has been proved that chitosan and its derivatives could offer outstanding antibacterial and hemostatic capabilities and help increase weight gain in the breeding of poultry. Herein, we put forward a novel strategy for the development of anti-coccidiosis drug formulations, aiming to synthesize 3-carboxyphenylboronic acid (CPBA) modified chitosan (CS) conjugates which could be self-assembled into polymeric micelles together with diclazuril (DIC), a poorly water-soluble coccidiostat drug, for site-specific drug release in the treatment of animal coccidiosis. The CPBA-modified micelles possessed specific glucose and pH dual-responsive capacity. The cumulative release of DIC reached the maximum of 85.0% at pH 6.8 and 50 mM glucose, while only 44.2% at pH 2.0 and no glucose, which allows drug to be released in the intestinal tract with neutral pH and glucose existence. 1H NMR and FTIR confirmed the successful synthesis of amphiphilic polymer; and the optimized DIC-loaded CS-CPBA micelles (DIC/CS-CPBA) shared nanoscale particle size of (118.9 ± 1.1) nm, drug loading of 8.97% and spherical shape. The pharmacokinetic results indicated that the AUC value of DIC/CS-CPBA micelles was 1.7 times than that of drug suspensions. The anti-coccidial efficacy demonstrated that DIC/CS-CPBA micelles improved the anticoccidial efficacy in vivo and reduced intestinal damage. These results indicated that phenylboronic acid-conjugated chitosan micelles provided a promising platform for specific-targeted drug release in the intestinal tract for the treatment of coccidiosis.
The clinical advancement of protein-based nanomedicine has revolutionized medical professionals' perspectives on cancer therapy. Protein-based nanoparticles have been exploited as attractive vehicles for cancer nanomedicine due to their unique properties derived from naturally biomacromolecules with superior biocompatibility and pharmaceutical features. Furthermore, the successful translation of Abraxane™ (paclitaxel-based albumin nanoparticles) into clinical application opened a new avenue for protein-based cancer nanomedicine. In this mini-review article, we demonstrate the rational design and recent progress of protein-based nanoparticles along with their applications in cancer diagnosis and therapy from recent literature. The current challenges and hurdles that hinder clinical application of protein-based nanoparticles are highlighted. Finally, future perspectives for translating protein-based nanoparticles into clinic are identified.
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