Treatment of colorectal cancer by anticancer and antibacterial effects of hemiprotonic phenanthroline-phenanthroline^(+) with nanomicelle delivery

Colorectal cancer(CRC)is a common digestive tract tumor worldwide.Specific microorganisms,including Fusobacterium nucleatum(F.nucleatum)and Escherichia coli(E.coli),are abundant in colonic mucosa and can promote the cancer progression and malignancy.Therefore,a therapeutic strategy is proposed to deliver effective drugs to colorectum for both anticancer and antibacteria.Here we used thin-film dispersionmethod to encapsulate hemiprotonic phenanthroline-phenanthroline^(+)(ph-ph^(+))into nanomicelle.The results showed that the drug-loading nanomicelle had good dispersion,and the particle size was about 28 nm.In vitro assay indicated that the nanomicelle was active against CRC-related obligate and facultative anaerobes.In human CRC cells,the nanomicelle could effectively inhibit cell proliferation and induce apoptosis.In vivo distribution showed that the nanomicelle could release ph-ph^(+) mainly in the colorectum.In CRC model mice,the nanomicelle significantly reduced tumor number and volume,and decreased the bacteria load and colorectal inflammation.Together,the study identifies that the ph-ph^(+) nanomicelle has the potential to apply in treating CRC,and also suggests that anticancer combined with antimicrobial therapy would be a feasible way for CRC therapy.

Twin evolution in cast Mg-Gd-Y alloys and its dependence on aging heat treatment

Effects of rare-earth(RE)and precipitates on twin evolution in cast Mg-10Gd-3Y-0.5Zr(wt.%)(GW103)alloys of solid solution(T4)and aged(T6)states are investigated performing quasi-static room temperature compression tests and microstructural characterization.It is found that both{10–12}and{11–21}extension twins(ET1 and ET2)can appear in the T4 and T6 states but with different emergence sequences.As the aging heat treatment leads to consumption of RE solutes which could inhibit atomic shuffling required for nucleation of ET1 but not ET2,ET2 occurs prior to ET1 in the T4 state,and ET1 emerges before ET2 in the T6 state.The extension twins here mainly coordinate the plastic deformation through the non-Schmid effect.Our results shed light on the influence of RE elements on twin evolution in magnesium alloys and have implications in developing high-performance Mg-RE alloys.

In vitro genotoxicity evaluation and metabolic study of residual glutaraldehyde in animal-derived biomaterials

Glutaraldehyde(GA)is an important additive that is mainly used in animal-derived biomaterials to improve their mechanical and antimicrobial capacities.However,GA chemical toxicity and the metabolic mechanism remain relatively unknown.Therefore,residual GA has always been a major health risk consideration for animal-derived medical devices.In this study,extracts of three biopatches were tested via the GA determination test and mouse lymphoma assay(MLA).The results showed that dissolved GA was a potential mutagen,which could induce significant cytotoxic and mutagenic effects in mouse lymphoma cells.These toxic reactions were relieved by the S9 metabolic activation(MA)system.Furthermore,we confirmed that GA concentration decreased and glutaric acid was generated during the catalytic process.We revealed GA could be oxidized via cytochrome P450 which was the main metabolic factor of S9.We found that even though GA was possibly responsible for positive reactions of animal-derived biomaterials’biocompatibility evaluation,it may not represent the real situation occurring in human bodies,owing to the presence of various detoxification mechanisms including the S9 system.Overall,in order to achieve a general balance between risk management and practical application,rational decisions based on comprehensive analyses must be considered.