首页|制备核壳型多功能纳米载体用于化疗-光热治疗乳腺癌

制备核壳型多功能纳米载体用于化疗-光热治疗乳腺癌

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通过对白色二氧化钛(TiO2)氢化还原处理,合成黑色二氧化钛(BT)作为光热制剂.以BT为内核,含双硫键的可降解型介孔有机硅(MON)为外壳,制备得到还原刺激响应性核壳型纳米复合材料(BT@M)作为药物载体.随后,利用BT@M的介孔结构负载化疗药物盐酸阿霉素(DOX·HCl),并引入pH响应性聚多巴胺(PDA)涂层作为"纳米阀",构建一类双重刺激响应性药物控释系统(BT@M/D-P)用于肿瘤化疗-光热联合治疗.透射电子显微镜(TEM)发现BT@M纳米颗粒呈现明显的核壳结构,尺寸约为100 nm;在含有10 mmol·L-1谷胱甘肽(GSH)的环境中,BT@M纳米颗粒由于二氧化硅外壳中的二硫键与GSH发生氧化还原反应发生断裂,导致外介孔有机二氧化硅壳层被分解.BT@M/D-P在模拟的肿瘤细胞和正常生理环境中具有pH和还原双重刺激响应性药物释放的特点.此外,在波长为808 nm的近红外光光照下,BT@M具有良好的光热稳定性,光热转换效率高达到35.5%.在特定波长光照下,BT@M/D-P将传统的化疗与"加热"肿瘤细胞的光热治疗相结合,产生明显高于正常细胞的肿瘤细胞毒性.相比单一的化疗或光热治疗,该纳米复合载药体系体现了对乳腺癌细胞的化疗-光热联合治疗效果.与此同时,BT@M/D-P在50~200 µg‧mL-1内不会出现溶血现象,具有良好的血液相容性.
Fabrication of multifunctional core-shell structured nanocarriers for chemo-photothermal therapy of breast cancer
Black titanium dioxide(BT)was first obtained by the hydrogenation and reduction of white titanium dioxide(TiO2),then a core-shell structured nanocomposite(BT@M)consisting of BT core and degradable mesoporous organosilica(MON)shell containing bisulfide bonds was prepared as redox-responsive drug delivery nanocarriers.Subsequently,chemotherapeutic drug doxorubicin hydrochloride(DOX·HCl)was loaded in the mesoporous BT@M,followed by introducing the pH-responsive polydopamine(PDA)coating to the surface as a"nanovalve",to fabricate a dual stimulus-responsive drug delivery nanosystem(BT@M/D-P)for tumor chemo-photothermal therapy.Transmission electron microscopy(TEM)images of BT@M nanoparticles exhibited a distinct core-shell structure with a size of about 100 nm.In a reductive environment containing 10 mmol·L-1 glutathione(GSH),BT@M nanoparticles underwent the redox-triggered decomposition of the outer mesoporous organosilica shell,due to the breakage of disulfide bonds in the organosilica framework.Furthermore,BT@M/D-P displayed pH/redox dual stimuli-responsive drug release in simulated tumor microenvironment and physiological environments.Under 808 nm laser illumination,BT@M exhibited excellent photothermal stability and high photothermal conversion efficiency up to 35.5%.Under specific-wavelength light irradiation,BT@M/D-P exerted significantly higher toxicity against tumor cells than normal cells,via effective combination of conventional chemotherapy and photothermal therapy which"heated up"tumor cells.Compared with chemotherapy or photothermal therapy alone,the nanocomplex-based drug delivery system displayed combined chemo-photothermal therapeutic effects for breast cancer cells.Meanwhile,BT@M/D-P nanoparticles did not induce hemolysis at the concentration range of 50-200 µg‧mL-1,suggesting good blood compatibility.

black titanium dioxidedegradable mesoporous organosilicacontrolled drug releasechemo-photothermal combination therapy

余金鑫、程崟家

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中南民族大学 化学与材料科学学院,武汉 430074

黑色二氧化钛 可降解介孔有机硅 药物可控释放 化疗-光热联合治疗

国家自然科学基金中央高校基本科研业务费专项

52173295CZQ23036

2024

中南民族大学学报(自然科学版)
中南民族大学

中南民族大学学报(自然科学版)

影响因子:0.536
ISSN:1672-4321
年,卷(期):2024.43(4)
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