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高分子抗肿瘤纳米药物的挑战与发展 被引量:12
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作者 孙瑞 邱娜莎 申有青 《高分子学报》 SCIE CAS CSCD 北大核心 2019年第6期588-601,共14页
抗肿瘤纳米药物的理想目标是降低毒副作用并提高疗效,但目前临床用纳米药物主要以显著降低药物毒性的优势获批进入临床.近年来,肿瘤分子靶向治疗、免疫治疗等高疗效方法的飞速发展,使提高疗效成为抗肿瘤纳米药物研究的当务之急.静脉注... 抗肿瘤纳米药物的理想目标是降低毒副作用并提高疗效,但目前临床用纳米药物主要以显著降低药物毒性的优势获批进入临床.近年来,肿瘤分子靶向治疗、免疫治疗等高疗效方法的飞速发展,使提高疗效成为抗肿瘤纳米药物研究的当务之急.静脉注射的纳米药物向实体肿瘤靶向输送过程是血液系统内循环、从血管外渗进入肿瘤组织和蓄积、肿瘤组织内渗透、肿瘤细胞内吞、胞内药物释放的五步'级联'递送过程(即CAPIR cascade).因此,如何设计载体高分子的功能,赋予纳米药物随血液系统、肿瘤组织和肿瘤细胞的微环境的变化而改变其纳米尺寸(size)、表面(surface)和稳定性(stability)(即3S nanoproperty transitions),从而满足肿瘤靶向输送过程中各步的要求以确保每一步具有高的效率,是获得高肿瘤靶向输送效率和高疗效的关键.本文将介绍利用各种响应高分子包括作者提出的电荷反转型高分子来设计具有上述3S纳米特性转换能力的高效纳米药物的方法,并总结了今后高分子纳米药物研究面临的挑战和发展趋势. 展开更多
关键词 纳米药物 功能高分子 肿瘤靶向输送 纳米特性转换 治疗性高分子 分子纳米药物
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Cytotoxicity and non-specific cellular uptake of bare and surface-modified upconversion nanoparticles in human skin cells 被引量:2
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作者 Anna E. Guller Alia N. Generalova +8 位作者 Elena V. Petersen Andrey V. Nechaev Inna A. Trusova Nikolay N. Landyshev Annemarie Nadort Ekaterina A. Grebenik Sergey M. Deyev Anatoly B. Shekhter Andrei V. Zvyagin 《Nano Research》 SCIE EI CAS CSCD 2015年第5期1546-1562,共17页
The cytotoxicity and non-specific cellular uptake of the most popular composition of upconversion nanoparticle (UCNP), NaYF4:Yb^3+:Er^3+, is reported using normal human skin cells, including dermal fibroblasts a... The cytotoxicity and non-specific cellular uptake of the most popular composition of upconversion nanoparticle (UCNP), NaYF4:Yb^3+:Er^3+, is reported using normal human skin cells, including dermal fibroblasts and immortalized human epidermal linear keratinocytes (HaCaT). A new hydrophilization reaction of as-synthesized UCNPs based on tetramethylammonium hydroxide (TMAH) enabled evaluation of the intrinsic cytotoxicity of bare UCNPs. The cytotoxicity effects of the UCNP surface-coating and polystyrene host were investigated over the concentration range 62.5-125 μg/mL with 24-h incubation, using a MTT test and optical microscopy. The fibroblast viability was not compromised by UCNPs, whereas the viability of keratinocytes varied from 52% ± 4% to 100% ± 10% than the control group, depending on the surface modification. Bare UCNPs reduced the keratinocyte viability to 76% ± 3%, while exhibiting profound non-specific cellular uptake. Hydrophilic poly(D,L-lactide)- and poly(maleic anhydride-alt-l-octadecene)-coated UCNPs were found to be least cytotoxic among the polymer-coated UCNPs, and were readily internalized by human skin cells. Polystyrene microbeads impregnated with UCNPs remained nontoxic. Surprisingly, no correlation was found between UCNP cytotoxicity and the internalization level in cells, although the latter ranged broadly from 0.03% to 59%, benchmarked against 100% uptake level of TMAH-UCNPs. 展开更多
关键词 nanoparticle UPCONVERSION surface modification biocompatibility CYTOTOXICITY human skin
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