Advances of nano-drug delivery systems in the prevention and control of drug-resistant pathogenic bacteria
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摘要:
抗菌药物的不规范使用和细菌选择性压力进化导致耐药病原菌日益增加，严重威胁畜禽养殖和公共卫生安全。随着纳米技术的发展，纳米药物递送系统在递送抗菌药物方面显示出一系列优势，如提高药物的生物利用度、减少毒副作用、降低药物使用成本等，为克服细菌耐药性提供了新的技术和策略。本文从畜禽耐药病原菌的危害及防治现状切入，综述纳米乳液、脂质体、固体脂质纳米粒、纳米胶束、金属纳米颗粒、纳米凝胶这6种纳米药物递送系统在耐药病原菌防控中的研究进展，以期为纳米药物递送系统在畜禽耐药病原菌防控中的应用提供借鉴，助力畜牧养殖业绿色可持续发展。
Abstract:The unregulated use of antimicrobial drugs and the evolution of bacterial selective pressure have led to an increasing number of drug-resistant pathogenic bacteria, which is a serious threat to livestock and poultry breeding as well as public health safety. With the development of nanotechnology, nano-drug delivery systems have shown a series of advantages in delivering antimicrobial drugs, such as improving the bioavailability of drugs, reducing the toxic side effects, and lowering the cost of drug use, which provide the new technologies and strategies for overcoming bacterial drug resistance. In this paper, we reviewed the progress of six nano-drug delivery system types of nanoemulsion, liposome, solid lipid nanoparticle, nano micelle, metal nanoparticle and nano gel in the prevention and control of drug-resistant pathogens, starting from the hazards of drug-resistant pathogens and the current status of their prevention and control in livestock and poultry. We expect to provide a reference for nano-drug delivery system application in the prevention and control of drug-resistant pathogen in livestock and poultry, and help the green and sustainable development of animal husbandry industry.
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红树林是在陆地与海洋交界带间重要的植物群落，受海水周期性浸淹，在改善滩涂环境、防风消浪、固岸护堤、增加海滩生物多样性、维系全球海洋生物资源等方面具有重要作用，被称为 “海洋卫士” [1-2]。福建省是我国红树林自然分布最北的省份，在我国红树林地理分布研究中具有特殊的地位[3]。近年来，红树林特殊生态环境下生存的异常丰富的微生物资源受到越来越多的关注，研究人员已从红树林中筛选到具有抗肿瘤、抗病毒、抗细菌等功能的多种微生物[4-6]，在医学领域展现出良好的应用潜力。然而，筛选和鉴定红树林中具有拮抗植物病原物活性的微生物资源的报道还较少，其优异的生防微生物资源有待进一步的挖掘和应用。
长期不合理使用农药造成环境污染、病原菌抗药性产生等诸多问题，严重制约了农业的可持续发展[7]。在日益重视环境保护的背景下，迫切需要挖掘新的生防资源，开发安全、高效、绿色环保的生防产品，以应对农业病虫害暴发与流行的威胁，维护全球粮食安全。芽孢杆菌Bacillus spp.是一类重要的植物病害生防资源，其生长速度快、营养需求简单，能够产生耐热、耐旱的内生孢子，有很强的抗逆能力，且不易产生抗药性，在植物病害绿色防控中具有广阔的应用前景。目前报道的主要生防芽孢杆菌包括枯草芽孢杆菌B. subtilis、蜡样芽孢杆菌B. cereus、苏云金芽孢杆菌B. thuringiensis、多黏类芽孢杆菌Paenibacillus polymyxa、短小芽孢杆菌B. pumilus等[8-10]。如从药用石豆兰中分离出枯草芽孢杆菌BBs-27对黄色镰刀菌有较强抑制作用[11]；短小芽孢杆菌KX-33种衣剂处理对棉花枯萎病的防效达到60.83%[12]。此外，一些芽孢杆菌具有广谱拮抗活性，能同时防治多种病害，如枯草芽孢杆菌的不同菌株QST713、GB03、MB1600和FZB24，其中QST713主要用于防治蔬菜、樱桃、葡萄、葫芦和胡桃病害，GB03和MB1600主要用于防治豆类、麦类、棉花和花生根部病， FZB24主要用于防治植物根腐病和枯萎病[13]；贝莱斯芽孢杆菌DJ1对白菜软腐病菌Pectobacterium carotovorum BC2、圆葱软腐病菌Burkholderia gladioli YC1、娃娃菜软腐病菌Pseudomonas sp. WWC2离体防效分别为84.30%、60.21%和69.96%，在防治蔬菜软腐病方面具有很好的应用潜能[14]。
本研究从福建省采集了8份红树林根际沉积物样品，从中筛选并获得10株对梨火疫病原细菌Erwinia amylovora具有良好拮抗活性的芽孢杆菌。选择其中拮抗活性最高的3株芽孢杆菌，分析其对水稻白叶枯病菌Xanthomonas oryzae pv. oryzae、番茄青枯病菌Ralstonia solanacearum、草莓炭疽病菌Colletotrichum gloeosporioides和小麦赤霉病菌Fusarium graminearum的抑制作用。本研究旨在为下一步高效绿色广谱生防菌株的开发和利用奠定理论基础。
1. 材料与方法
1.1 材料
所用菌株：梨火疫病菌、番茄青枯病菌、水稻白叶枯病菌、草莓炭疽病菌、小麦赤霉病菌，均来自中国农业科学院植物保护研究所植物病虫害综合治理全国重点实验室。
样品采集：2023年5月于福建漳州采集了8份红树林(秋茄Kandelia candel和白骨壤Avicennia marina混植林)根际沉积物样品，每份样品约200 g，装于密封袋，室温保存。
培养基：固体NA培养基(蛋白胨10 g，牛肉膏3 g，氯化钠5 g，琼脂15 g，蒸馏水
1000 mL，pH 7.4)；固体LB培养基(胰蛋白胨10 g，酵母提取物5 g，琼脂15 g，蒸馏水1000 mL，pH 7.2)；PSA培养基(蛋白胨10 g，蔗糖10 g，谷氨酸1 g，琼脂15 g，蒸馏水1000 mL，pH 7.0)；PDA培养基(马铃薯200 g，葡萄糖20 g，琼脂15 g，蒸馏水1000 mL，pH 7.0)。液体培养基配方为相应固体培养基中不加琼脂。1.2 方法
1.2.1 拮抗菌初筛
参照刘国红等[15]方法，称取土壤样品10 g，加入装有90 mL无菌水的三角瓶，振荡摇匀后80 ℃水浴10 min，水浴期间摇匀2~3次，使之水浴充分，即配成10−1浓度的稀释液，作为土壤悬液原液。将土壤悬液原液继续稀释为10−2、10−3和10−4 3个浓度梯度，吸取200 µL不同浓度梯度的土壤悬浮液，涂布到事先倒好含梨火疫病菌(1.0×106 CFU/mL)的NA平板上，每个浓度梯度重复3次，待涂布好的平板晾干后放入28 ℃恒温培养箱静置培养48 h，随后对着光观察平板上的抑菌圈，挑取有抑菌圈的菌株，在新的LB平板上划线培养48 h，得到纯培养物。将纯化后的菌株接种到LB液体培养基中，28 ℃、180 r/min震荡培养过夜后，与50%(φ)甘油溶液按体积比1∶1混匀，于−80 ℃保存。
1.2.2 拮抗菌的复筛
将得到的对梨火疫病菌具有拮抗作用的菌株在LB固体培养基上活化后，用直径为0.5 cm的打孔器打菌饼，随后将菌饼挑至含梨火疫病菌的NA固体培养基上，28 ℃恒温静置培养48 h，测量并记录抑菌圈直径，每个处理重复3次。
1.2.3 拮抗菌的分类鉴定
将筛选得到的菌株在LB液体培养基上28 ℃、180 r/min震荡培养24 h，收集菌体，参照细菌DNA提取试剂盒(DP302-02，天根生化科技有限公司)说明书提取基因组DNA，以芽孢杆菌16S rDNA通用引物27F(AGAGTTTGATCCTGGCTCAG)和1492R(TACGACTTAACCCCAATCGC)进行PCR扩增。扩增产物经10 g/L琼脂糖凝胶电泳检测合格后，送北京六合华大基因科技有限公司进行测序，所得序列通过EzBioCloud数据库(https://www.ezbiocloud.net/)进行在线比对，以相似性最高菌株的序列作为参比对象，参照鲁晏宏等[16]方法，采用MEGA6.0软件对各菌株的系统发育地位进行分析。
将菌株PBIB1、PBIB4和PBIB7在LB液体培养基上28 ℃、180 r/min震荡培养24 h，收集菌体，参照细菌DNA提取试剂盒(DP302-02，天根生化科技有限公司)说明书提取基因组DNA。将菌株基因组DNA送至北京赛默百合生物科技有限公司进行基因组测序，并进行比对分析，最终鉴定PBIB1、PBIB4和PBIB7。
1.2.4 拮抗菌对其他病原菌的拮抗活性测定
对病原细菌的拮抗活性测定：将芽孢杆菌在LB固体培养基上活化后，用打孔器打取直径为0.5 cm的菌饼，分别放置在含番茄青枯病菌(1.0×106 CFU/mL)的NA固体培养基和含水稻白叶枯病菌(1.0×106 CFU/mL)的PSA固体培养基上，28 ℃恒温静置培养48 h，测量并记录抑菌圈直径，每个处理重复3次。
对病原真菌的拮抗活性测定：将病原真菌在PDA固体培养基上28 ℃恒温静置培养5 d后，用打孔器打取直径为0.5 cm的菌饼，放置在新鲜的PDA平板中间；将准备好的芽孢杆菌菌饼围绕病原真菌呈三角形放置，于28 ℃恒温静置培养5 d，测量病菌半径(r)，并计算抑制率。以只放置病原菌菌饼的PDA平板为对照，每个处理重复3次。
$$ \text { 抑菌率 }=\left(r_{\text {对照 }}-r_{\text {处理 }}\right) / r_{\text {对照 }} \times 100 {\text{%}} 。 $$ (1) 1.2.5 室内防效测定
对梨火疫病菌的室内防效测定：参照Kharadi等[17]方法，挑取新鲜的芽孢杆菌和梨火疫病菌，分别在LB液体培养基和NA液体培养基中，28 ℃、180 r/min震荡培养24 h，测定菌液浓度并调至D600 nm=1.0。将等体积的芽孢杆菌和梨火疫病菌混合，取10 µL混合菌液接种在库尔勒香梨上，分别接种3 g/L四霉素(辽宁微科生物工程有限公司)
1000 倍稀释液和梨火疫病菌混合液、生防菌，以只接种病原菌为阳性对照，以只接种无菌水为阴性对照。试验重复3次，每次每个处理接种5个梨。将接种后的梨放置于28 ℃静置，5 d后和7 d后分别拍照记录发病情况，并于7 d后计算防治效果。对草莓炭疽病菌的室内防效测定：参照Ma等[18]方法，将草莓炭疽病菌在PDA固体培养基上，28 ℃培养8 d，刮取菌丝放入适量无菌水中，用无菌涂布棒搅拌混匀，4层无菌纱布过滤，采用血球计数板统计滤液中的孢子浓度，用无菌水将孢子浓度稀释至1.0×106 CFU/mL，备用。挑取新鲜的芽孢杆菌，在LB液体培养基中28 ℃、180 r/min震荡培养48 h，测定菌液浓度并调至D600 nm=1.0。将等体积的草莓炭疽病菌孢子悬浮液和芽孢杆菌菌悬液混合，吸取10 µL注射至草莓叶片上，同时设只接种生防菌处理，以只接种病原菌为阳性对照，以只接无菌水处理为阴性对照。试验重复3次，每次每个处理接种10片叶片。将接种后的叶片放置于28 ℃静置并保湿，第4 天和第6 天分别拍照记录发病情况，并于第6 天根据病斑直径(d)计算防效。
$$ \text { 防效 }=\left(d_{\text {阳性对照 }}-d_{\text {处理 }}\right) / d_{\text {阳性对照 }} \times 100 {\text{%}} \text { 。 } $$ (2) 1.2.6 数据分析
数据采用SPSS软件进行单因素方差分析中的Duncan’s法进行显著性分析。
2. 结果与分析
2.1 拮抗菌筛选
通过对采集的8份土样初筛，共获得10个对梨火疫病菌具有拮抗作用的菌株。采用平板对峙法对得到的10个菌株的抑菌能力进行复筛，以抑菌圈直径的大小表示拮抗能力的强弱。结果(图1)显示，菌株PBIB4和PBIB1的抑菌作用最强，抑菌圈直径分别为4.23和4.17 cm；其次为PBIB9和PBIB7，抑菌圈直径分别为4.07和3.70 cm；有8个菌株对梨火疫病菌的抑菌圈直径超过3 cm，占总筛选菌株总数的80%。
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图 1 生防芽孢杆菌菌株对梨火疫病菌的拮抗作用柱子上方的不同小写字母表明差异显著(P<0. 05， Duncan’s法)。Figure 1. Antagonistic effects of biocontrol Bacillus strains on Erwinia amylovoraDifferent lowercase letters on bars indicate significant differences (P<0. 05，Duncan’s method).2.2 拮抗菌的分类鉴定
对所得的10个拮抗菌株分别提取基因组DNA，以16S rDNA引物进行PCR 扩增，对获得的序列进行测序，得到的测序结果提交NCBI数据库进行比对，选择相似度较高的模式菌株序列以及测序获得的序列构建系统发育树。结果(图2)显示，所得10个菌株均为芽孢杆菌，其中PBIB1、PBIB2、PBIB4、PBIB5、PBIB6和PBIB9初步鉴定为贝莱斯芽孢杆菌B. velezensis，PBIB3为席勒氏短芽孢杆菌B. schisleri，PBIB7 和PBIB8为特基拉芽孢杆菌B. tequilensis或枯草芽孢杆菌，PBIB10为多黏类芽孢杆菌。
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图 2 基于16S rDNA基因序列构建的拮抗芽孢杆菌系统发育树Figure 2. Phylogenetic tree of antagonist Bacillus strains based on 16S rDNA gene sequences为进一步鉴定这些芽孢杆菌，我们挑选对梨火疫病菌拮抗效果较好的3株菌PBIB1、PBIB4和PBIB7，提取其基因组并进行测序分析。测序结果和NCBI基因组数据库进行比对，结果显示，PBIB1(BioSample accessions：SAMN40965255)、PBIB4(BioSample accessions：SAMN40965255)和PBIB7(BioSample accessions：SAMN40965255)分别与贝莱斯芽孢杆菌SF334、贝莱斯芽孢杆菌AD8和枯草芽孢杆菌YB-15的序列相似性最高，分别为99.85%、99.99%和99.78%，表明PBIB1和PBIB4为贝莱斯芽孢杆菌，PBIB7为枯草芽孢杆菌。
2.3 拮抗菌对番茄青枯病菌和水稻白叶枯病菌的拮抗活性
为进一步测定所得拮抗菌株对植物病原细菌的抑制效果，选择生产上对蔬菜和水稻威胁严重的2种病原细菌番茄青枯病菌和水稻白叶枯病菌，检测PBIB1、PBIB4和PBIB7对其的拮抗活性。平板拮抗试验结果(图3)显示，这3个芽孢杆菌对番茄青枯病菌和水稻白叶枯病菌均具有拮抗作用，其中，PBIB1、PBIB4和PBIB7对番茄青枯病菌的抑菌圈直径分别为3.15、3.20和2.85 cm，对水稻白叶枯病菌的抑菌圈直径分别为5.80、5.95和4.50 cm。
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图 3 3株芽孢杆菌对番茄青枯病菌和水稻白叶枯病菌的拮抗活性Figure 3. Antagonistic activities of three Bacillus strains against Ralstonia solanacearum and Xanthomonas oryzae pv. oryzae2.4 拮抗菌对草莓炭疽病菌和小麦赤霉病菌的拮抗活性
为进一步检测所得拮抗菌株的抑菌谱，本研究采用平板对峙法，测定了PBIB1、PBIB4和PBIB7对重要的植物病原真菌草莓炭疽病菌和小麦赤霉病菌的拮抗作用。结果(图4)显示，PBIB1、PBIB4和PBIB7对2个病原真菌均具有明显的拮抗作用，三者对草莓炭疽病菌的抑菌率分别为86.77%、82.09%和76.40%，对小麦赤霉病菌的抑菌率分别为78.89%、71.85%和65.93%(表1)。
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图 4 3株芽孢杆菌对草莓炭疽病菌和小麦赤霉病菌的拮抗活性Figure 4. Antagonistic activities of three Bacillus strains against Colletotrichum gloeosporioides and Fusarium graminearum表 1 3株芽孢杆菌对草莓炭疽病菌和小麦赤霉病菌的抑菌率1)Table 1. Inhibition rates of three Bacillus strains against Colletotrichum gloeosporioides and Fusarium graminearum% 菌株 Strain 草莓炭疽病菌 C. gloeosporioides 小麦赤霉病菌 F. graminearum PBIB1 86.77±1.83a 78.89±3.33a PBIB4 82.09±1.33ab 71.85±1.28b PBIB7 76.40±1.86b 65.93±2.57c 1) 同列数据后的不同小写字母表示差异显著(P<0. 05， Duncan’s法)。
1) Different lowercase letters in the same column indicate significant differences (P<0. 05，Duncan’s method).2.5 拮抗菌对梨火疫病的室内防效
对梨火疫病室内防效测定结果(图5)显示，接种5和7 d后，拮抗菌和四霉素均能显著抑制火疫病菌侵染梨果实。进一步分析(表2)表明，接种7 d后，PBIB1和PBIB4对梨火疫病防治效果最好，分别为82.83%和78.84%；其次为PBIB7，对梨火疫病的防治效果68.86%。此外，对照组四霉素处理对梨火疫病的防效为63.87%。
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图 5 3株芽孢杆菌对梨火疫病的室内防效1：Erwinia amylovora；2：PBIB1+E. amylovora；3：PBIB4+E. amylovora；4：PBIB7+E. amylovora；5：四霉素Tetramycin+E. amylovor；6：ddH2O。Figure 5. Control effects of three Bacillus strains on fire blight in greenhouse表 2 不同处理后梨火疫病病斑直径和防效Table 2. The lesion diameters and the control effects on fire blight after different treatments处理 Treatment 病斑直径/cm
Disease spot diameter防效1)/%
Control effectPBIB1 0 PBIB1+Erwinia amylovora 0.28±0.03 82.83±1.17a PBIB4 0 PBIB4+E. amylovora 0.35±0.09 78.84±4.56a PBIB7 0 PBIB7+E. amylovora 0.51±0.08 68.86±3.82b E. amylovora 1.67±0.06 四霉素+E. amylovora Tetramycin+E. amylovora 0.60±0.08 63.87±4.03b ddH2O 0 1) 同列数据后的不同小写字母表示差异显著(P<0. 05， Duncan’s法)。
1) Different lowercase letters in the same column indicate significant differences (P<0. 05，Duncan’s method).2.6 拮抗菌对草莓炭疽病的室内防效
对草莓炭疽病室内防效测定结果(图6)显示，接种4和6 d后，拮抗菌均能显著抑制炭疽病菌侵染草莓叶片。进一步分析(表3)表明接种6 d后， PBIB1和PBIB4对草莓炭疽病的防治效果最好，分别为92.31%和90.38%； PBIB7次之，对草莓炭疽病的防治效果为67.30%。
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图 6 3株芽孢杆菌对草莓炭疽病的室内防效Figure 6. Control effect of three Bacillus strains on strawberry anthracnose in greenhouse表 3 不同处理后草莓炭疽病病斑直径和防效Table 3. The lesion diameters and the control effects on strawberry anthracnose after different treatments处理
Treatment病斑直径/cm
Disease spot diameter防效1)/%
Control effectPBIB1 0 PBIB1+Colletotrichum gloeosporioides 0.13±0.05 92.31±3.03a PBIB4 0 PBIB4+C. gloeosporioides 0.17±0.06 90.38±3.67a PBIB7 0 PBIB7+C. gloeosporioides 0.57±0.09 67.30±4.88b C. gloeosporioides 1.73±0.12 ddH2O 0 1) 同列数据后的不同小写字母表示差异显著(P<0. 05， Duncan’s法)。
1) Different lowercase letters in the same column indicate significant differences (P<0. 05，Duncan’s method).3. 讨论与结论
红树林复杂而独特的生态系统决定了其微生物的多样性及资源的珍稀性[19]。研究表明，细菌是红树林生态系统中最主要的微生物类群，其次是真菌，放线菌和微型藻类相对较少[20]。崔莹等[21]在海南红树林土壤中分离到155株芽孢杆菌，分属21个遗传类群，显示出海南红树林土壤中芽孢杆菌丰富的遗传多样性。本研究以梨火疫病菌为生防靶标，在8份福建红树林沉积物中特异筛选到10株具有拮抗活性的芽孢杆菌。16S rDNA鉴定结果显示，这10株菌分属于贝莱斯芽孢杆菌、席勒氏短芽孢杆菌、特基拉芽孢杆菌或枯草芽孢杆菌，以及多黏类芽孢杆菌等，表明福建红树林沉积物中具有丰富的生防资源。戴悦等[22]在广东省湛江市红树林根际土壤中筛选到107株对动物病原细菌有拮抗作用的菌株，其中肠杆菌属占比最多，为69.2%，其次为芽孢杆菌属，占比为15.9%。本研究特异性筛选了芽孢杆菌，而对红树林中其他类型生防资源的挖掘与利用，还有待下一步的研究。
梨火疫病是我国进境植物检疫危险性病害，于2016年入侵我国新疆地区[23-24]。目前，我国种植的梨树多为梨火疫病感病品种，尤其是经济价值较高的库尔勒香梨，对梨火疫病表现为高感[25]。基于近年对绿色环保的要求，农用链霉素产品已全部退出我国市场[26]，因此急需开发高效绿色的生防产品，以应对梨火疫病流行风险。本研究对筛选到的3株生防芽孢杆菌进行梨火疫病室内防效测定，结果显示，PBIB1、PBIB4和PBIB7对梨火疫病的防治效果分别为82.83%、78.84%和68.86%。下一步将以这3株菌为基础，重点研究其抑菌机制，优化其发酵条件，为开发梨火疫病的生防制剂打好基础。
在田间环境下，由多种病原菌复合侵染导致的病害较为常见，和单一病原菌侵染引起的病害相比，其造成的损失要更加严重，且防控难度高[27]。如不同尖孢镰刀菌专化型复合侵染引起的番茄枯萎病[28]，黑点根腐病菌和镰孢菌复合侵染引起的甜瓜根腐病[29]，围小丛壳菌与葡萄座腔菌复合侵染引起茶褐枯病等[30]。在新疆梨园中，也观察到火疫病菌和轮纹病菌共同侵染导致梨树发病的现象。利用广谱拮抗活性的生防菌是防治复合侵染病害的有效手段。本研究对PBIB1、PBIB4和PBIB7的进一步分析显示，其对番茄青枯病菌、水稻白叶枯病菌、草莓炭疽病菌、小麦赤霉病菌等主要作物病原菌均具有很好的拮抗作用，且对草莓炭疽病菌的盆栽防效分别为92.31%、90.38%和67.30%，表明PBIB1、PBIB4和PBIB7具有作为广谱拮抗菌的应用潜力。
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图 1 纳米药物递送系统优势示意图
Figure 1. Schematic diagram of the advantages of nano-drug delivery systems
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图 2 6种纳米药物递送系统示意图
Figure 2. Schematic diagram of six kinds of nano-drug delivery systems
表 1 不同纳米药物递送系统及其特点
Table 1 Different nano-drug delivery systems and their features
种类
Type优点
Advantage缺点
Disadvantage装载药物
Loading drug病原体
Pathogen抑菌机制
Antibacterial mechanism参考文献
Reference纳米乳液
Nanoemulsion水相、油相混合，增加药物溶解度；提高药物生物利用度 工艺成本相对较高；不稳定，保质期较短 己醛、壳聚糖 副溶血性弧菌 细菌形态变化并破坏细胞膜 [101] 香芹酚 大肠埃希菌、肠炎沙门氏菌 提高香芹酚的生物活性 [102] 脂质体
Liposome封装水、脂溶性药物；提高药物稳定性；延长作用时间；减少药物不良反应 整体稳定性较差；生物利用度低；易引发免疫或毒性反应 妥布霉素 铜绿假单胞菌 增强破坏生物膜的能力 [103] 橄榄叶、橙皮提取物 金黄色葡萄球菌 提高组成成分的抗菌活性 [104] 氨苄西林 藤黄微球菌 提高氨苄西林的稳定性和抗菌活性 [105] 固体脂质纳米颗粒
Solid lipid nanoparticle改善生物利用度；保护药物免受酶分解或其他环境因素的破坏；实现缓慢持续的药物释放 长期储存稳定性差；可能引起细胞毒性；给药途径有限 多黏菌素B 铜绿假单胞菌 增加多黏菌素B的溶解度，增强对细菌细胞膜的作用 [106] 乳链菌肽 齿垢密螺旋体 保护乳链菌肽不被降解，延长作用时间 [107] 利福平 铜绿假单胞菌 抑制铜绿假单胞生物膜形成 [108] 纳米胶束
Nano micelle提高药物的生物利用度和溶解度；减少药物的副作用和毒性；有效改善药物的稳定性和溶解性 制备过程较复杂，成本较高；稳定性和储存性较差 脱氧胆酸、壳聚糖 大肠埃希菌、金黄色葡萄球菌 破坏细胞膜 [109] 纳米银、儿茶酚功能化季铵化壳聚糖 大肠埃希菌、金黄色葡萄球菌 靶向细菌，光热联合杀菌 [110] 金属纳米颗粒
Metal nanoparticle高效的杀菌能力；通过尺寸、形状、浓度等参数来调整抗菌性能 高浓度对机体有一定的毒性，易在体内蓄积；易发生沉淀、团聚 银、铜 大肠埃希菌、金黄色葡萄球菌 促进细菌活性氧产生 [111] 银、磺胺嘧啶 大肠埃希菌、金黄色葡萄球菌 提高磺胺嘧啶水溶性，增强磺胺嘧啶的释放和抗菌活性 [112] 纳米氧化铜、纳米氧化锌 大肠埃希菌、金黄色葡萄球菌、耐甲氧西林金黄色葡萄球菌 协同抗菌作用，促进细菌活性氧产生；引起脂质过氧化 [113] 纳米凝胶
Nano gel提供反应、吸附和催化活性位点，提高材料性能；通过改变反应条件控制其大小、形状和孔径等参数 合成过程复杂；性能易受温度、湿度、pH等因素影响 过氧化物酶 大肠埃希菌、金黄色葡萄球菌 消耗谷胱甘肽 [114] 茴香精油 金黄色葡萄球菌 药物与载体之间存在特殊互作，增强与药物的接触 [115] 纳米氧化锌 铜绿假单胞菌、金黄色葡萄球菌、大肠埃希菌 与纳米氧化锌协同抗菌 [116] 
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[1] VARELA M F, STEPHEN J, LEKSHMI M, et al. Bacterial resistance to antimicrobial agents[J]. Antibiotics, 2021, 10(5): 593. doi: 10.3390/antibiotics10050593.
[2] THEURETZBACHER U, OUTTERSON K, ENGEL A, et al. The global preclinical antibacterial pipeline[J]. Nature Reviews Microbiology, 2020, 18(5): 275-285. doi: 10.1038/s41579-019-0288-0
[3] MANCUSO G, MIDIRI A, GERACE E, et al. Bacterial antibiotic resistance: The most critical pathogens[J]. Pathogens, 2021, 10(10): 1310. doi: 10.3390/pathogens10101310.
[4] MIETHKE M, PIERONI M, WEBER T, et al. Towards the sustainable discovery and development of new antibiotics[J]. Nature Reviews Chemistry, 2021, 5(10): 726-749. doi: 10.1038/s41570-021-00313-1
[5] ELERAKY N E, ALLAM A, HASSAN S B, et al. Nanomedicine fight against antibacterial resistance: An overview of the recent pharmaceutical innovations[J]. Pharmaceutics, 2020, 12(2): 142. doi: 10.3390/pharmaceutics12020142.
[6] MOFFO F, MOUICHE M M M, DJOMGANG H K, et al. Poultry litter contamination by Escherichia coli resistant to critically important antimicrobials for human and animal use and risk for public health in Cameroon[J]. Antibiotics, 2021, 10(4): 402. doi: 10.3390/antibiotics10040402.
[7] SARAIVA M D S, LIM K, DO MONTE D F M, et al. Antimicrobial resistance in the globalized food chain: A One Health perspective applied to the poultry industry[J]. Brazilian Journal of Microbiology, 2022, 53(1): 465-486. doi: 10.1007/s42770-021-00635-8
[8] HEDMAN H D, VASCO K A, ZHANG L. A review of antimicrobial resistance in poultry farming within low-resource settings[J]. Animals, 2020, 10(8): 1264. doi: 10.3390/ani10081264.
[9] LEÓN-BUITIMEA A, GARZA-CÁRDENAS C R, GARZA-CERVANTES J A, et al. The demand for new antibiotics: Antimicrobial peptides, nanoparticles, and combinatorial therapies as future strategies in antibacterial agent design[J]. Frontiers in Microbiology, 2020, 11: 1669. doi: 10.3389/fmicb.2020.01669.
[10] 马天玥, 朱尤卓, 余冰欣, 等. 抗菌肽的作用机制与临床应用研究进展[J]. 抗感染药学, 2023, 20(5): 447-452. [11] DĄBROWSKA K, ABEDON S T. Pharmacologically aware phage therapy: Pharmacodynamic and pharmacokinetic obstacles to phage antibacterial action in animal and human bodies[J]. Microbiology and Molecular Biology Reviews, 2019, 83(4): e00012-19. doi: 10.1128/MMBR.00012-19
[12] 董晨扬, 魏曼琳, 张航, 等. 植物提取物在动物生产中的研究进展[J]. 饲料研究, 2022, 45(4): 136-139. [13] HAJIPOUR M J, FROMM K M, AKBAR ASHKARRAN A, et al. Antibacterial properties of nanoparticles[J]. Trends in Biotechnology, 2012, 30(10): 499-511. doi: 10.1016/j.tibtech.2012.06.004
[14] WANG Y, YANG Y, SHI Y, et al. Antibiotic-free antibacterial strategies enabled by nanomaterials: Progress and perspectives[J]. Advanced Materials, 2020, 32(18): e1904106. doi: 10.1002/adma.201904106
[15] LOIRA-PASTORIZA C, TODOROFF J, VANBEVER R. Delivery strategies for sustained drug release in the lungs[J]. Advanced Drug Delivery Reviews, 2014, 75: 81-91. doi: 10.1016/j.addr.2014.05.017
[16] HOCHVALDOVÁ L, VEČEŘOVÁ R, KOLÁŘ M, et al. Antibacterial nanomaterials: Upcoming hope to overcome antibiotic resistance crisis[J]. Nanotechnology Reviews, 2022, 11(1): 1115-1142. doi: 10.1515/ntrev-2022-0059
[17] WANG Y, ZHANG Y, SU R, et al. Antimicrobial therapy based on self-assembling peptides[J]. Journal of Materials Chemistry B, 2024, 12(21): 5061-5075. doi: 10.1039/D4TB00260A
[18] MOREIRA L, GUIMARÃES N M, SANTOS R S, et al. Promising strategies employing nucleic acids as antimicrobial drugs[J]. Molecular Therapy-Nucleic Acids, 2024, 35(1): 102122. doi: 10.1016/j.omtn.2024.102122.
[19] PANDEY P, GULATI N, MAKHIJA M, et al. Nanoemulsion: A novel drug delivery approach for enhancement of bioavailability[J]. Recent Patents on Nanotechnology, 2020, 14(4): 276-293. doi: 10.2174/1872210514666200604145755
[20] GARCIA C R, MALIK M H, BISWAS S, et al. Nanoemulsion delivery systems for enhanced efficacy of antimicrobials and essential oils[J]. Biomaterials Science, 2022, 10(3): 633-653. doi: 10.1039/D1BM01537K
[21] MOGHIMI R, GHADERI L, RAFATI H, et al. Superior antibacterial activity of nanoemulsion of Thymus daenensis essential oil against E. coli[J]. Food Chemistry, 2016, 194: 410-415. doi: 10.1016/j.foodchem.2015.07.139
[22] RYU V, MCCLEMENTS D J, CORRADINI M G, et al. Natural antimicrobial delivery systems: Formulation, antimicrobial activity, and mechanism of action of quillaja saponin-stabilized carvacrol nanoemulsions[J]. Food Hydrocolloids, 2018, 82: 442-450. doi: 10.1016/j.foodhyd.2018.04.017
[23] MOHAMED M A, NASR M, ELKHATIB W F, et al. In vitro evaluation of antimicrobial activity and cytotoxicity of different nanobiotics targeting multidrug resistant and biofilm forming Staphylococci[J]. BioMed Research International, 2018, 2018: 7658238. doi: 10.1155/2018/7658238.
[24] MOGHIMI R, ALIAHMADI A, RAFATI H, et al. Antibacterial and anti-biofilm activity of nanoemulsion of Thymus daenensis oil against multi-drug resistant Acinetobacter baumannii[J]. Journal of Molecular Liquids, 2018, 265: 765-770. doi: 10.1016/j.molliq.2018.07.023
[25] CONFESSOR M V A, AGRELES M A A, CAMPOS L A D, et al. Olive oil nanoemulsion containing curcumin: Antimicrobial agent against multidrug-resistant bacteria[J]. Applied Microbiology and Biotechnology, 2024, 108(1): 241. doi: 10.1007/s00253-024-13057-x.
[26] HASHEM A H, DOGHISH A S, ISMAIL A, et al. A novel nanoemulsion based on clove and thyme essential oils: Characterization, antibacterial, antibiofilm and anticancer activities[J]. Electronic Journal of Biotechnology, 2024, 68: 20-30. doi: 10.1016/j.ejbt.2023.12.001
[27] 陈小楠, 申元娜, 李彭宇, 等. 细菌生物膜的特征及抗细菌生物膜策略[J]. 药学学报, 2018, 53(12): 2040-2049. [28] MOHAMED H R H, EL-SHAMY S, ABDELGAYED S S, et al. Modulation efficiency of clove oil nano-emulsion against genotoxic, oxidative stress, and histological injuries induced via titanium dioxide nanoparticles in mice[J]. Scientific Reports, 2024, 14(1): 7715. doi: 10.1038/s41598-024-57728-1.
[29] OZTURK B, ARGIN S, OZILGEN M, et al. Formation and stabilization of nanoemulsion-based vitamin E delivery systems using natural surfactants: Quillaja saponin and lecithin[J]. Journal of Food Engineering, 2014, 142: 57-63. doi: 10.1016/j.jfoodeng.2014.06.015
[30] AZEEM A, RIZWAN M, AHMAD F J, et al. Nanoemulsion components screening and selection: A technical note[J]. Aaps Pharmscitech, 2009, 10(1): 69-76. doi: 10.1208/s12249-008-9178-x
[31] 吴毅, 金少鸿. 药用辅料吐温80的药理、药动学及分析方法研究进展[J]. 中国药事, 2008, 22(8): 717-720. [32] 李秀英, 曾凡, 赵曜, 等. 脂质体药物递送系统的研究进展[J]. 中国新药杂志, 2014, 23(16): 1904-1911. [33] ZHANG H, WANG G, YANG H. Drug delivery systems for differential release in combination therapy[J]. Expert Opinion on Drug Delivery, 2011, 8(2): 171-190. doi: 10.1517/17425247.2011.547470
[34] MIRZAIE A, PEIROVI N, AKBARZADEH I, et al. Preparation and optimization of ciprofloxacin encapsulated niosomes: A new approach for enhanced antibacterial activity, biofilm inhibition and reduced antibiotic resistance in ciprofloxacin-resistant methicillin-resistance Staphylococcus aureus[J]. Bioorganic Chemistry, 2020, 103: 104231. doi: 10.1016/j.bioorg.2020.104231.
[35] GHOSH R, DE M. Liposome-based antibacterial delivery: An emergent approach to combat bacterial infections[J]. ACS Omega, 2023, 8(39): 35442-35451. doi: 10.1021/acsomega.3c04893
[36] SCHEEDER A, BROCKHOFF M, WARD E N, et al. Molecular mechanisms of cationic fusogenic liposome interactions with bacterial envelopes[J]. Journal of the American Chemical Society, 2023, 145(51): 28240-28250. doi: 10.1021/jacs.3c11463
[37] GUO R, LIU Y, LI K, et al. Direct interactions between cationic liposomes and bacterial cells ameliorate the systemic treatment of invasive multidrug-resistant Staphylococcus aureus infections[J]. Nanomedicine: Nanotechnology, Biology and Medicine, 2021, 34: 102382. doi: 10.1016/j.nano.2021.102382.
[38] WANG Y. Liposome as a delivery system for the treatment of biofilm-mediated infections[J]. Journal of Applied Microbiology, 2021, 131(6): 2626-2639. doi: 10.1111/jam.15053
[39] DYMEK M, SIKORA E. Liposomes as biocompatible and smart delivery systems: The current state[J]. Advances in Colloid and Interface Science, 2022, 309: 102757. doi: 10.1016/j.cis.2022.102757.
[40] HERRERA C V, O’CONNOR P M, RATREY P, et al. Anionic liposome formulation for oral delivery of thuricin CD, a potential antimicrobial peptide therapeutic[J]. International Journal of Pharmaceutics, 2024, 654: 123918. doi: 10.1016/j.ijpharm.2024.123918.
[41] SINGH S, SINGH S K, CHOWDHURY I, et al. Understanding the mechanism of bacterial biofilms resistance to antimicrobial agents[J]. The Open Microbiology Journal, 2017, 11: 53-62. doi: 10.2174/1874285801711010053
[42] RAO Y, SUN Y Y, HU H Y, et al. Hypoxia-sensitive adjuvant loaded liposomes enhance the antimicrobial activity of azithromycin via phospholipase-triggered releasing for Pseudomonas aeruginosa biofilms eradication[J]. International Journal of Pharmaceutics, 2022, 623: 121910. doi: 10.1016/j.ijpharm.2022.121910.
[43] BARRAUD N, HASSETT D J, HWANG S H, et al. Involvement of nitric oxide in biofilm dispersal of Pseudomonas aeruginosa[J]. Journal of Bacteriology, 2006, 188(21): 7344-7353. doi: 10.1128/JB.00779-06
[44] CUTRUZZOLÀ F, FRANKENBERG-DINKEL N. Origin and impact of nitric oxide in Pseudomonas aeruginosa biofilms[J]. Journal of Bacteriology, 2016, 198(1): 55-65. doi: 10.1128/JB.00371-15
[45] MANCONI M, CADDEO C, MANCA M L, et al. Oral delivery of natural compounds by phospholipid vesicles[J]. Nanomedicine, 2020, 15(18): 1795-1803. doi: 10.2217/nnm-2020-0085
[46] WANG X, CHENG F, WANG X, et al. Chitosan decoration improves the rapid and long-term antibacterial activities of cinnamaldehyde-loaded liposomes[J]. International Journal of Biological Macromolecules, 2021, 168: 59-66. doi: 10.1016/j.ijbiomac.2020.12.003
[47] BOZZUTO G, MOLINARI A. Liposomes as nanomedical devices[J]. International Journal of Nanomedicine, 2015, 10: 975-999.
[48] XU M, HU Y, XIAO Y, et al. Near-infrared-controlled nanoplatform exploiting photothermal promotion of peroxidase-like and OXD-like activities for potent antibacterial and anti-biofilm therapies[J]. ACS Applied Materials & Interfaces, 2020, 12(45): 50260-50274.
[49] VIEGAS C, PATRÍCIO A B, PRATA J M, et al. Solid lipid nanoparticles vs. nanostructured lipid carriers: A comparative review[J]. Pharmaceutics, 2023, 15(6): 1593. doi: 10.3390/pharmaceutics15061593.
[50] GHADERKHANI J, YOUSEFIMASHOUF R, ARABESTANI M, et al. Improved antibacterial function of Rifampicin-loaded solid lipid nanoparticles on Brucella abortus[J]. Artificial Cells, Nanomedicine, and Biotechnology, 2019, 47(1): 1181-1193. doi: 10.1080/21691401.2019.1593858
[51] SEVERINO P, CHAUD M V, SHIMOJO A, et al. Sodium alginate-cross-linked polymyxin B sulphate-loaded solid lipid nanoparticles: Antibiotic resistance tests and HaCat and NIH/3T3 cell viability studies[J]. Colloids and Surfaces B: Biointerfaces, 2015, 129: 191-197. doi: 10.1016/j.colsurfb.2015.03.049
[52] SINGH M, SCHIAVONE N, PAPUCCI L, et al. Streptomycin sulphate loaded solid lipid nanoparticles show enhanced uptake in macrophage, lower MIC in Mycobacterium and improved oral bioavailability[J]. European Journal of Pharmaceutics and Biopharmaceutics, 2021, 160: 100-124. doi: 10.1016/j.ejpb.2021.01.009
[53] SCIOLI MONTOTO S, MURACA G, RUIZ M E. Solid lipid nanoparticles for drug delivery: Pharmacological and biopharmaceutical aspects[J]. Frontiers in Molecular Biosciences, 2020, 7: 587997. doi: 10.3389/fmolb.2020.587997.
[54] ANJUM M M, PATEL K K, DEHARI D, et al. Anacardic acid encapsulated solid lipid nanoparticles for Staphylococcus aureus biofilm therapy: Chitosan and DNase coating improves antimicrobial activity[J]. Drug Delivery and Translational Research, 2021, 11(1): 305-317. doi: 10.1007/s13346-020-00795-4
[55] COSTA A, SARMENTO B, SEABRA V. Mannose-functionalized solid lipid nanoparticles are effective in targeting alveolar macrophages[J]. European Journal of Pharmaceutical Sciences, 2018, 114: 103-113. doi: 10.1016/j.ejps.2017.12.006
[56] DOLATABADI J E N, OMIDI Y. Solid lipid-based nanocarriers as efficient targeted drug and gene delivery systems[J]. TrAC-Trends in Analytical Chemistry, 2016, 77: 100-108. doi: 10.1016/j.trac.2015.12.016
[57] LI X Z, PLÉSIAT P, NIKAIDO H. The challenge of efflux-mediated antibiotic resistance in Gram-negative bacteria[J]. Clinical Microbiology Reviews, 2015, 28(2): 337-418. doi: 10.1128/CMR.00117-14
[58] GONZÁLEZ-PAREDES A, SITIA L, RUYRA A, et al. Solid lipid nanoparticles for the delivery of anti-microbial oligonucleotides[J]. European Journal of Pharmaceutics and Biopharmaceutics, 2019, 134: 166-177. doi: 10.1016/j.ejpb.2018.11.017
[59] HIBBITTS A, LUCÍA A, SERRANO-SEVILLA I, et al. Co-delivery of free vancomycin and transcription factor decoy-nanostructured lipid carriers can enhance inhibition of methicillin resistant Staphylococcus aureus (MRSA)[J]. PLoS One, 2019, 14(9): e0220684. doi: 10.1371/journal.pone.0220684
[60] BERMUDEZ L E M, WU M, YOUNG L S. Intracellular killing of Mycobacterium avium complex by rifapentine and liposome-encapsulated amikacin[J]. The Journal of Infectious Diseases, 1987, 156(3): 510-513. doi: 10.1093/infdis/156.3.510
[61] TAWFIK S M, AZIZOV S, ELMASRY M R, et al. Recent advances in nanomicelles delivery systems[J]. Nanomaterials, 2020, 11(1): 70. doi: 10.3390/nano11010070.
[62] MOHAMED S, PARAYATH N N, TAURIN S, et al. Polymeric nano-micelles: Versatile platform for targeted delivery in cancer[J]. Therapeutic Delivery, 2014, 5(10): 1101-1121. doi: 10.4155/tde.14.69
[63] YANG X, QIU Q, LIU G, et al. Traceless antibiotic-crosslinked micelles for rapid clearance of intracellular bacteria[J]. Journal of Controlled Release, 2022, 341: 329-340. doi: 10.1016/j.jconrel.2021.11.037
[64] LU C, XIAO Y, LIU Y, et al. Hyaluronic acid-based levofloxacin nanomicelles for nitric oxide-triggered drug delivery to treat bacterial infections[J]. Carbohydrate Polymers, 2020, 229: 115479. doi: 10.1016/j.carbpol.2019.115479.
[65] GAO Q, HUANG D, DENG Y, et al. Chlorin e6 (Ce6)-loaded supramolecular polypeptide micelles with enhanced photodynamic therapy effect against Pseudomonas aeruginosa[J]. Chemical Engineering Journal, 2021, 417: 129334. doi: 10.1016/j.cej.2021.129334.
[66] MORTEZA M, ROYA S, HAMED H, et al. Synthesis and evaluation of polymeric micelle containing piperacillin/tazobactam for enhanced antibacterial activity[J]. Drug Delivery, 2019, 26(1): 1292-1299. doi: 10.1080/10717544.2019.1693708
[67] PARK S C, KO C, HYEON H, et al. Imaging and targeted antibacterial therapy using chimeric antimicrobial peptide micelles[J]. ACS Applied Materials & Interfaces, 2020, 12(49): 54306-54315.
[68] GUPTA C, HAZRA C, PODDAR P, et al. Development and performance evaluation of self-assembled pH-responsive curcumin-bacterial exopolysaccharide micellar conjugates as bioactive delivery system[J]. International Journal of Biological Macromolecules, 2024, 263: 130372. doi: 10.1016/j.ijbiomac.2024.130372.
[69] SOUSA A, BORØY V, BÆVERUD A, et al. Polymyxin B stabilized DNA micelles for sustained antibacterial and antibiofilm activity against P. aeruginosa[J]. Journal of Materials Chemistry B, 2023, 11(33): 7972-7985. doi: 10.1039/D3TB00704A
[70] JAMKHANDE P G, GHULE N W, BAMER A H, et al. Metal nanoparticles synthesis: An overview on methods of preparation, advantages and disadvantages, and applications[J]. Journal of Drug Delivery Science and Technology, 2019, 53: 101174. doi: 10.1016/j.jddst.2019.101174.
[71] 何盈盈, 周文铂, 邰启炜, 等. 纳米材料和纳米药物递释系统在抗细菌感染中的应用及机制[J]. 药学学报, 2023, 58(1): 106-117. [72] SONDI I, SALOPEK-SONDI B. Silver nanoparticles as antimicrobial agent: A case study on E. coli as a model for gram-negative bacteria[J]. Journal of Colloid and Interface Science, 2004, 275(1): 177-182. doi: 10.1016/j.jcis.2004.02.012
[73] SANPUI P, MURUGADOSS A, DURGA PRASAD P V, et al. The antibacterial properties of a novel chitosan-Ag-nanoparticle composite[J]. International Journal of Food Microbiology, 2008, 124(2): 142-146. doi: 10.1016/j.ijfoodmicro.2008.03.004
[74] PAL S, TAK Y K, SONG J M. Does the antibacterial activity of silver nanoparticles depend on the shape of the nanoparticle? A study of the Gram-negative bacterium Escherichia coli[J]. Applied and Environmental Microbiology, 2007, 73(6): 1712-1720. doi: 10.1128/AEM.02218-06
[75] ZHU M, LIU X, TAN L, et al. Photo-responsive chitosan/Ag/MoS2 for rapid bacteria-killing[J]. Journal of Hazardous Materials, 2020, 383: 121122. doi: 10.1016/j.jhazmat.2019.121122.
[76] YANG Y, WU X, HE C, et al. Metal-organic framework/Ag-based hybrid nanoagents for rapid and synergistic bacterial eradication[J]. ACS Applied Materials & Interfaces, 2020, 12(12): 13698-13708.
[77] XIE X, SUN T, XUE J, et al. Ag nanoparticles cluster with pH-triggered reassembly in targeting antimicrobial applications[J]. Advanced Functional Materials, 2020, 30(17): 2000511. doi: 10.1002/adfm.202000511.
[78] REZVANI E, RAFFERTY A, MCGUINNESS C, et al. Adverse effects of nanosilver on human health and the environment[J]. Acta Biomaterialia, 2019, 94: 145-159. doi: 10.1016/j.actbio.2019.05.042
[79] ZHANG J, WANG F, YALAMARTY S S K, et al. Nano silver-induced toxicity and associated mechanisms[J]. International Journal of Nanomedicine, 2022, 17: 1851-1864. doi: 10.2147/IJN.S355131
[80] ZHANG W, LIU X, BAO S, et al. Evaluation of nano-specific toxicity of zinc oxide, copper oxide, and silver nanoparticles through toxic ratio[J]. Journal of Nanoparticle Research, 2016, 18(12): 372. doi: 10.1007/s11051-016-3689-2.
[81] DUTTA R K, NENAVATHU B P, GANGISHETTY M K, et al. Studies on antibacterial activity of ZnO nanoparticles by ROS induced lipid peroxidation[J]. Colloids and Surfaces B: Biointerfaces, 2012, 94: 143-150. doi: 10.1016/j.colsurfb.2012.01.046
[82] KUMAR R, UMAR A, KUMAR G, et al. Antimicrobial properties of ZnO nanomaterials: A review[J]. Ceramics International, 2017, 43(5): 3940-3961. doi: 10.1016/j.ceramint.2016.12.062
[83] XIANG Y, ZHOU Q, LI Z, et al. A Z-scheme heterojunction of ZnO/CDots/C3N4 for strengthened photoresponsive bacteria-killing and acceleration of wound healing[J]. Journal of Materials Science & Technology, 2020, 57: 1-11.
[84] VELSANKAR K, VENKATESAN A, MUTHUMARI P, et al. Green inspired synthesis of ZnO nanoparticles and its characterizations with biofilm, antioxidant, anti-inflammatory, and anti-diabetic activities[J]. Journal of Molecular Structure, 2022, 1255: 132420. doi: 10.1016/j.molstruc.2022.132420.
[85] RUANGTONG J, T-THIENPRASERT J, T-THIENPRASERT N P. Green synthesized ZnO nanosheets from banana peel extract possess anti-bacterial activity and anti-cancer activity[J]. Materials Today Communications, 2020, 24: 101224. doi: 10.1016/j.mtcomm.2020.101224.
[86] SALAMA S A, ESSAM D, TAGYAN A I, et al. Novel composite of nano zinc oxide and nano propolis as antibiotic for antibiotic-resistant bacteria: A promising approach[J]. Scientific Reports, 2024, 14(1): 20894. doi: 10.1038/s41598-024-70490-8.
[87] JABIR M S, RASHID T M, NAYEF U M, et al. Inhibition of Staphylococcus aureus α-hemolysin production using nanocurcumin capped Au@ZnO nanocomposite[J]. Bioinorganic Chemistry and Applications, 2022, 2022: 2663812. doi: 10.1155/2022/2663812.
[88] XAVIER J, COSTA P, HISSA D, et al. Evaluation of the microbial diversity and heavy metal resistance genes of a microbial community on contaminated environment[J]. Applied Geochemistry, 2019, 105: 1-6. doi: 10.1016/j.apgeochem.2019.04.012
[89] NANDA M, KUMAR V, SHARMA D. Multimetal tolerance mechanisms in bacteria: The resistance strategies acquired by bacteria that can be exploited to ‘clean-up’ heavy metal contaminants from water[J]. Aquatic Toxicology, 2019, 212: 1-10. doi: 10.1016/j.aquatox.2019.04.011
[90] DWEBA C C, ZISHIRI O T, EL ZOWALATY M E. Methicillin-resistant Staphylococcus aureus: Livestock-associated, antimicrobial, and heavy metal resistance[J]. Infection and Drug Resistance, 2018, 11: 2497-2509. doi: 10.2147/IDR.S175967
[91] LU J, WANG Y, JIN M, et al. Both silver ions and silver nanoparticles facilitate the horizontal transfer of plasmid-mediated antibiotic resistance genes[J]. Water Research, 2020, 169: 115229. doi: 10.1016/j.watres.2019.115229.
[92] DUAN Q Y, ZHU Y X, JIA H R, et al. Nanogels: Synthesis, properties, and recent biomedical applications[J]. Progress in Materials Science, 2023, 139: 101167. doi: 10.1016/j.pmatsci.2023.101167.
[93] KESKIN D, ZU G, FORSON A M, et al. Nanogels: A novel approach in antimicrobial delivery systems and antimicrobial coatings[J]. Bioactive Materials, 2021, 6(10): 3634-3657. doi: 10.1016/j.bioactmat.2021.03.004
[94] QI X, HUANG Y, YOU S, et al. Engineering robust Ag-decorated polydopamine nano-photothermal platforms to combat bacterial infection and prompt wound healing[J]. Advanced Science, 2022, 9(11): 2106015. doi: 10.1002/advs.202106015.
[95] HUANG B, LIU X, LI Z, et al. Rapid bacteria capturing and killing by AgNPs/N-CD@ZnO hybrids strengthened photo-responsive xerogel for rapid healing of bacteria-infected wounds[J]. Chemical Engineering Journal, 2021, 414: 128805. doi: 10.1016/j.cej.2021.128805.
[96] LUO W, MENG K, ZHAO Y, et al. Guar gum modified tilmicosin-loaded sodium alginate/gelatin composite nanogels for effective therapy of porcine proliferative enteritis caused by Lawsonia intracellularis[J]. International Journal of Biological Macromolecules, 2023, 242: 125084. doi: 10.1016/j.ijbiomac.2023.125084.
[97] JIA P, ZOU Y, JIANG J. Antibacterial, antioxidant and injectable hydrogels constructed using CuS and curcumin co-loaded micelles for NIR-enhanced infected wound healing[J]. Journal of Materials Chemistry B, 2023, 11(47): 11319-11334. doi: 10.1039/D3TB02278A
[98] FESSEHA Y A, MANAYIA A H, LIU P C, et al. Photoreactive silver-containing supramolecular polymers that form self-assembled nanogels for efficient antibacterial treatment[J]. Journal of Colloid and Interface Science, 2024, 654: 967-978. doi: 10.1016/j.jcis.2023.10.119
[99] MAO J Y, MISCEVIC D, UNNIKRISHNAN B, et al. Carbon nanogels exert multipronged attack on resistant bacteria and strongly constrain resistance evolution[J]. Journal of Colloid and Interface Science, 2022, 608: 1813-1826. doi: 10.1016/j.jcis.2021.10.107
[100] LIN H Y, WANG S W, MAO J Y, et al. Carbonized nanogels for simultaneous antibacterial and antioxidant treatment of bacterial keratitis[J]. Chemical Engineering Journal, 2021, 411: 128469. doi: 10.1016/j.cej.2021.128469.
[101] FAN Q, YAN X, JIA H, et al. Antibacterial properties of hexanal-chitosan nanoemulsion against Vibrio parahaemolyticus and its application in shelled shrimp preservation at 4 ℃[J]. International Journal of Biological Macromolecules, 2024, 257: 128614. doi: 10.1016/j.ijbiomac.2023.128614.
[102] DA SILVA B D, DO ROSÁRIO D K A, NETO L T, et al. Antioxidant, antibacterial and antibiofilm activity of nanoemulsion-based natural compound delivery systems compared with non-nanoemulsified versions[J]. Foods, 2023, 12(9): 1901. doi: 10.3390/foods12091901.
[103] ALZAHRANI N M, BOOQ R Y, ALDOSSARY A M, et al. Liposome-encapsulated tobramycin and IDR-1018 peptide mediated biofilm disruption and enhanced antimicrobial activity against Pseudomonas aeruginosa[J]. Pharmaceutics, 2022, 14(5): 960. doi: 10.3390/pharmaceutics14050960.
[104] PREVETE G, CARVALHO L G, CARMEN RAZOLA-DIAZ M D, et al. Ultrasound assisted extraction and liposome encapsulation of olive leaves and orange peels: How to transform biomass waste into valuable resources with antimicrobial activity[J]. Ultrasonics Sonochemistry, 2024, 102: 106765. doi: 10.1016/j.ultsonch.2024.106765.
[105] SCHUMACHER I, MARGALIT R. Liposome-encapsulated ampicillin: Physicochemical and antibacterial properties[J]. Journal of Pharmaceutical Sciences, 1997, 86(5): 635-641. doi: 10.1021/js9503690
[106] SEVERINO P, SILVEIRA E F, LOUREIRO K, et al. Antimicrobial activity of polymyxin-loaded solid lipid nanoparticles (PLX-SLN): Characterization of physicochemical properties and in vitro efficacy[J]. European Journal of Pharmaceutical Sciences, 2017, 106: 177-184. doi: 10.1016/j.ejps.2017.05.063
[107] RADAIC A, MALONE E, KAMARAJAN P, et al. Solid lipid nanoparticles loaded with nisin (SLN-nisin) are more effective than free nisin as antimicrobial, antibiofilm, and anticancer agents[J]. Journal of Biomedical Nanotechnology, 2022, 18(4): 1227-1235. doi: 10.1166/jbn.2022.3314
[108] KHORRAMDEL M, GHADIKOLAII F P, HASHEMY S I, et al. Nanoformulated meloxicam and rifampin: Inhibiting quorum sensing and biofilm formation in Pseudomonas aeruginosa[J]. Nanomedicine, 2024, 19(7): 615-632. doi: 10.2217/nnm-2023-0268
[109] QI Y, CHEN Q, CAI X, et al. Self-assembled amphiphilic chitosan nanomicelles: Synthesis, characterization and antibacterial activity[J]. Biomolecules, 2023, 13(11): 1595. doi: 10.3390/biom13111595.
[110] ZHANG H, YU S, WU S, et al. Rational design of silver NPs-incorporated quaternized chitin nanomicelle with combinational antibacterial capability for infected wound healing[J]. International Journal of Biological Macromolecules, 2023, 224: 1206-1216. doi: 10.1016/j.ijbiomac.2022.10.206
[111] XIE Y, CHEN S, PENG X, et al. Alloyed nanostructures integrated metal-phenolic nanoplatform for synergistic wound disinfection and revascularization[J]. Bioactive Materials, 2022, 16: 95-106. doi: 10.1016/j.bioactmat.2022.03.004
[112] LUO T, SHAKYA S, MITTAL P, et al. Co-delivery of superfine nano-silver and solubilized sulfadiazine for enhanced antibacterial functions[J]. International Journal of Pharmaceutics, 2020, 584: 119407. doi: 10.1016/j.ijpharm.2020.119407.
[113] FRANCIS D V, JAYAKUMAR M N, AHMAD H, et al. Antimicrobial activity of biogenic metal oxide nanoparticles and their synergistic effect on clinical pathogens[J]. International Journal of Molecular Sciences, 2023, 24(12): 9998. doi: 10.3390/ijms24129998.
[114] ZHANG S, HAO J, DING F, et al. Nanocatalyst doped bacterial cellulose-based thermosensitive nanogel with biocatalytic function for antibacterial application[J]. International Journal of Biological Macromolecules, 2022, 195: 294-301. doi: 10.1016/j.ijbiomac.2021.12.020
[115] ALAM A, FOUDAH A, SALKINI M, et al. Herbal fennel essential oil nanogel: Formulation, characterization and antibacterial activity against Staphylococcus aureus[J]. Gels, 2022, 8(11): 736. doi: 10.3390/gels8110736.
[116] TAMADDON F, BAGHERI F, AHMADI-AHMADABADI E. Selective preparation of crystalline or fibrous nano-cellulose carboxylate to fabricate an anti-bacterial hydrogel in co-operation with ZnO and recycled gelatin[J]. International Journal of Biological Macromolecules, 2023, 242: 124922. doi: 10.1016/j.ijbiomac.2023.124922.
[117] ARSÈNE M M J, DAVARES A K L, VIKTOROVNA P I, et al. The public health issue of antibiotic residues in food and feed: Causes, consequences, and potential solutions[J]. Veterinary World, 2022, 15(3): 662-671.
[118] PATRA J K, DAS G, FRACETO L F, et al. Nano based drug delivery systems: Recent developments and future prospects[J]. Journal of Nanobiotechnology, 2018, 16(1): 71. doi: 10.1186/s12951-018-0392-8.
[119] AHIRE K, GORLE A, MAHARASHTRA I. An overview on methods of preparation and characterization of nanoemulsion[J]. World Journal of Pharmacy and Pharmaceutical Sciences, 2021, 10(8): 897-908.
[120] FAN Y, MARIOLI M, ZHANG K. Analytical characterization of liposomes and other lipid nanoparticles for drug delivery[J]. Journal of Pharmaceutical and Biomedical Analysis, 2021, 192: 113642. doi: 10.1016/j.jpba.2020.113642.
[121] BOSE A, ROY BURMAN D, SIKDAR B, et al. Nanomicelles: Types, properties and applications in drug delivery[J]. IET Nanobiotechnology, 2021, 15(1): 19-27. doi: 10.1049/nbt2.12018
[122] RIZVI S A A, SALEH A M. Applications of nanoparticle systems in drug delivery technology[J]. Saudi Pharmaceutical Journal, 2018, 26(1): 64-70. doi: 10.1016/j.jsps.2017.10.012
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