A triple stimuli-responsive noncovalent graft copolymer was designed and synthesized by the host–guest interactions between β-CD grafted dextran and ferrocene-terminated poly(lactide).
A series of fluoroalkyl end-capped diblock copolymers of poly[2-(N,N-dimethylamino)ethyl methacrylate] (PDMAEMA or PDMA) and poly[2-(N,N-diethylamino)ethyl methacrylate] (PDEAEMA or PDEA) have been synthesized via oxyanion-initiated polymerization, in which a potassium alcoholate of 4,4,5,5,6,6,7,7,7-nonafluoro-1-heptanol (NFHOK) was used as an initiator. The chemical structures of the NFHO-PDMA-b-PDEA and NFHO-PDEA-b-PDMA depended on the addition sequence of the two monomers and the feeding molar ratios of [DMA] to [DEA] during the polymerization process. These copolymers have been characterized by 1H NMR and 19F NMR spectroscopy and gel permeation chromatography (GPC). The aggregation behavior of these copolymers in aqueous solutions at different pH media was studied using a combination of surface tension, fluorescence probe, and transmission electron microscopy (TEM). Both diblock copolymers exhibited distinct pH/temperature-responsive properties. The critical aggregation concentrations (cacs) of these copolymers have been investigated, and the results showed that these copolymers possess excellent surface activity. Besides, these fluoroalkyl end-capped diblock copolymers showed pH-induced lower critical solution temperatures (LCSTs) in water. TEM analysis indicated that the NFHO-PDMA30-b-PDEA10 diblock copolymers can self-assemble into the multicompartment micelles in aqueous solutions under basic conditions, in which the pH value is higher than the pKa values of both PDMA and PDEA homopolymers, while the NFHO-PDEA10-b-PDMA30 diblock copolymers can form flowerlike micelles in basic aqueous solution.
A facile route for DNA encapsulation in triggered intracellular degradable polymer microcapsules has been achieved via electrostatic interaction, using a polycation, that is, poly[(dimethylamino)ethyl methacrylate] end-capped with cholesterol moiety (Chol-PDMAEMA30), along with a polyanion named MePEG2000-block-poly(methacrylic acid) carring partial thiol groups (MePEG2000-b-PMAASH). The encapsulation procedure involves three steps: (i) DNA was first complexed with the polycation (Chol-PDMAEMA30); (ii) the complex was then further set into interaction with the anion-containing MePEG2000-b-PMAASH; and (iii) the compound carrier was subsequently obtained by cross-linking the thiol groups of the MePEG2000-b-PMAASH to form disulfide linkages. The interactions between every pair among calf thymus DNA, Chol-PDMAEMA30, and MePEG2000-b-PMAASH were studied by agarose gel retardation assay and ethidium bromide displacement assay. The results indicate that the prepared microcapsules may remain stable during systemic circulation, but degrade and release the carried DNA in a cellular reducing environment. Furthermore, the biophysical properties of the microcapsule have been investigated by ζ-potential, laser light scattering, and transmission electron microscopy (TEM) measurements.
The selective anti-tumor activity and less toxic nature of hypoxia-activated prodrugs including tirapazamine (TPZ) are harbored by hypoxia levels in tumors, the inadequacy of which leads to failure in clinical trials. Thus, the development of effective clinical applications of TPZ requires advanced strategies to intensify hypoxia levels in tumors effectively and safely. In this study, we designed and fabricated a paclitaxel (PTX)-loaded dual-response delivery system with a low dose (e.g., 2 Gy) of X-ray and reactive oxygen species on the basis of diselenide block copolymers. Upon the external X-ray stimulus, the system accurately released encapsulated PTX at tumor sites and remarkably improved tumor hypoxia levels by causing severe damage to tumor blood vessels. Subsequently, these enhanced tumor hypoxia levels effectively activated the reduction of TPZ into benzotriazinyl free radicals, which significantly improved the antitumor efficacy of our system against 4T1 breast cancer cells with an initial tumor volume of 500 mm3. Moreover, the dual-stimulus coordinated and controlled release of PTX was found to largely avoid the off-target effects of PTX on normal cells while exhibiting very limited side effects in experimental mice. The current novel strategy for regulating tumor hypoxia levels offers an effective and safe way to activate TPZ for the treatment of large solid tumors.
An acid-cleavable and fluorescent block copolymer with good biocompatibility has been prepared and applied as a co-delivery carrier of DNA and doxorubicin.
A vector tabu search algorithm encapsulating a new updating mechanism for current states and a directed search phase is proposed to enhance its searching ability for Pareto-optimal solutions. The new updating mechanism considers quantitatively both the number of improved objectives and the amount of improvements in a specified objective, of multiobjective design problems. The directed search phase uses some desired directions, a priori knowledge about the objective space, as the moving direction to efficiently find improved solutions without any gradient computation procedure. The numerical results on both high- and low-frequency inverse problems are reported to demonstrate the pros and cons of the proposed algorithm. It is observed that the proposed vector tabu search method outperforms its ancestors in both the convergence performance and the solution quality.
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