Construction of multifunctional stimuli-responsive nanotherapeutics enabling improved intratumoral penetration of therapeutics and reversal of multiple-drug resistance (MDR) is potent to achieve effective cancer treatment. Herein, we report a general method to synthesize pH-dissociable calcium carbonate (CaCO3) hollow nanoparticles with amorphous CaCO3 as the template, gallic acid (GA) as the organic ligand, and ferrous ions as the metallic center via a one-pot coordination reaction. The obtained GA–Fe@CaCO3 exhibits high loading efficiencies to both oxidized cisplatin prodrug and doxorubicin, yielding drug loaded GA–Fe@CaCO3 nanotherapeutics featured in pH-responsive size shrinkage, drug release, and Fenton catalytic activity. Compared to nonresponsive GA–Fe@silica nanoparticles prepared with silica nanoparticles as the template, such GA–Fe@CaCO3 confers significantly improved intratumoral penetration capacity. Moreover, both types of drug-loaded GA–Fe@CaCO3 nanotherapeutics exhibit synergistic therapeutic efficacies to corresponding MDR cancer cells because of the GA–Fe mediated intracellular oxidative stress amplification that could reduce the efflux of engulfed drugs by impairing the mitochondrial-mediated production of adenosine triphosphate (ATP). As a result, it is found that the doxorubicin loaded GA–Fe@CaCO3 exhibits superior therapeutic effect towards doxorubicin-resistant 4T1 breast tumors via combined chemodynamic and chemo-therapies. This work highlights the preparation of pH-dissociable CaCO3-based nanotherapeutics to enable effective tumor penetration for enhanced treatment of drug-resistant tumors.
For many-objective optimization problems, how to get a set of solutions with good convergence and diversity is a difficult and challenging work. In this paper, a new decomposition based evolutionary algorithm with uniform designs is proposed to achieve the goal. The proposed algorithm adopts the uniform design method to set the weight vectors which are uniformly distributed over the design space, and the size of the weight vectors neither increases nonlinearly with the number of objectives nor considers a formulaic setting. A crossover operator based on the uniform design method is constructed to enhance the search capacity of the proposed algorithm. Moreover, in order to improve the convergence performance of the algorithm, a sub-population strategy is used to optimize each sub-problem. Comparing with some efficient state-of-the-art algorithms, e.g., NSGAII-CE, MOEA/D and HypE, on six benchmark functions, the proposed algorithm is able to find a set of solutions with better diversity and convergence. 相似文献
The genetic diversity of 5 populations of Jatropha curcas L. (Euphorbiaceae), a species cultivated in tropical countries and used in biodiesel production, was analyzed by amplified fragment length polymorphism (AFLP). Plants from distinct populations found in the State of São Paulo, Brazil, had their genetic diversity characterized by using three primer combinations. The number of polymorphic bands obtained reached 184 and the base pair length of bands ranged from 75 to 350, with average PIC values of 0.418. Accessions from the Aguas de Santa Barbara population presented the highest percentage of polymorphic loci (89.76%), followed by the populations of Catanduva (84.24%), Jales (80.98%), Jurucê (78.80%) and Taquaritinga (70.65%). Plants collected from the populations of Taquaritinga and Jales presented the smallest and highest genetic diversities, respectively, measured by using both Nei's genetic variability index (h = 0.2242 and 0.2973) and Shannon's index (I = 0.3359 and 0.4319). The results obtained indicated that 73.1% of genetic variability corresponds to intrapopulational variation and 26.8% to variation among populations. The clustering dendrogram using Jacquard showed four clusters. Three clusters with low genetic diversity grouped most of individuals collected in distinct regions (63.3% JU, 47.0% JA and 82.5% TA) and the fourth with the higher genetic diversity was composed with basically individuals collected in CA and AS, but it also had samples collected in JU, JA and TA, where it is possible to select individuals to be included in breeding programs. 相似文献