背景:近年来研究者开发了各种高分子纳米粒子作为抗肿瘤药物载体,并利用纳米粒子的优势,例如血液循环时间延长、肿瘤内选择性聚集等,提高对骨肉瘤的疗效。目的:基于最新的相关研究,对高分子纳米药物在骨肉瘤治疗方面的应用及其发展前景...背景:近年来研究者开发了各种高分子纳米粒子作为抗肿瘤药物载体,并利用纳米粒子的优势,例如血液循环时间延长、肿瘤内选择性聚集等,提高对骨肉瘤的疗效。目的:基于最新的相关研究,对高分子纳米药物在骨肉瘤治疗方面的应用及其发展前景作以综述。方法:作者应用计算机检索Web of Science、NCBI和PubMed生物医学数据库,检索时间为1900年至2019年6月,以“osteosarcoma;polymer;nanoparticle;controlled drug delivery;tumor therapy”为检索关键词,初检文章265篇,筛选后将107篇文章纳入高分子纳米药物治疗骨肉瘤的相关研究报道。结果与结论:骨肉瘤是最常见的恶性骨肿瘤,主要影响儿童和青少年,早期远处肺转移和局部高侵袭性使骨肉瘤患者长期生存率降低。虽然化疗提高了骨肉瘤患者的生存率,但其应用潜力因严重不良反应和耐药性受到限制。与传统化疗相比,高分子纳米药物不仅降低了对正常组织的毒副作用,而且还能够延长体内循环时间,使化疗药物在肿瘤部位持续缓慢释放,从而提高了治疗效果。因此高分子纳米药物对于骨肉瘤的治疗具有巨大的应用前景。展开更多
The clinical translation of nanomedicines has been strongly hampered by the limitations of delivery vehicles,promoting scientists to search for novel nanocarriers.Although cell membrane-based delivery systems have att...The clinical translation of nanomedicines has been strongly hampered by the limitations of delivery vehicles,promoting scientists to search for novel nanocarriers.Although cell membrane-based delivery systems have attracted extensive attention,further functionalizations are urgently desired to augment their theranostic functions.We propose a cell-friendly supramolecular strategy to engineer cell membranes utilizing cyclodextrin-based host–guest molecular recognitions to fix the defects arising from chemical and genetic modifcations.In this study,the supramolecular cell membrane vesicles(SCMVs)specifcally accumulate in tumors,benefting from tumor-homing capability and the enhanced permeability and retention effect.SCMVs co-delivering indocyanine green and an indoleamine 2,3-dioxygenase inhibitor effectively ablate tumors combining photodynamic therapy and immunotherapy.Driven by host–guest inclusion complexation,SCMVs successfully encapsulate resiquimod to repolarize tumor-associated macrophages into M1 phenotype,synergizing with immune checkpoint blockade therapy.This supramolecular engineering methodology based on noncovalent interactions presents a generalizable and cell-friendly tactic to develop living cell–originated nanomaterials for precise cancer therapy.展开更多
Biodegradable polymeric nanoparticles are more and more frequently used in drug delivery systems, which represent one of the most rapidly developing areas. In our previous study, a novel natural hybrid polyester, poly...Biodegradable polymeric nanoparticles are more and more frequently used in drug delivery systems, which represent one of the most rapidly developing areas. In our previous study, a novel natural hybrid polyester, polyethylene glycol 200 （PEG200） end-capped poly （3-hydroxybutyrate-co-3-hydroxyhcxanoate） （PHBHHx-PEG） was directly produced by Aeromonas hydrophila fermentation. In this study, the performance of the novel biodegradable PHBHHx-PEG copolyester as a sustained release carrier for hydrophobic drugs with different molecular weights and the in vitro sustained release profile were investigated. 5-Fluorouracil （5-Fu, Mw=130.1）, TGX221 （Mw=364.4）, and Rapamycin （RAP, Mw=914.2） were used as the model drugs. PHBHHx-PEG nanoparticles entrapped with 5-Fu, TGX221 and RAP were fabricated by a modified emulsification/solvent evaporation method, respectively. The average diameter of 5-Fu, TGX221, and RAP loaded PHBHHx-PEG nanoparticles was between 198.2-217.4 nm, and the entrapment efficiency of the three drugs was 62.5%, 93.4% and 91.9%, respectively. The in vitro release profiles of 5-Fu, TGX221 and RAP from PHBHHx-PEG nanoparticles were different. 5-Fu showed faster release rate and an obvious initial burst release phase. TGX221 and RAP were demonstrated to be released more slowly and steadily. The release percentages of 5-Fu, TGX221 and RAP were 97.7%, 85.1% and 74.7% after releasing for 72 h. PHBHHx-PEG is a kind of promising material as a carrier for the entrapment and delivery of hydrophobic drugs especially for those drugs with high molecular weight.展开更多
文摘背景:近年来研究者开发了各种高分子纳米粒子作为抗肿瘤药物载体,并利用纳米粒子的优势,例如血液循环时间延长、肿瘤内选择性聚集等,提高对骨肉瘤的疗效。目的:基于最新的相关研究,对高分子纳米药物在骨肉瘤治疗方面的应用及其发展前景作以综述。方法:作者应用计算机检索Web of Science、NCBI和PubMed生物医学数据库,检索时间为1900年至2019年6月,以“osteosarcoma;polymer;nanoparticle;controlled drug delivery;tumor therapy”为检索关键词,初检文章265篇,筛选后将107篇文章纳入高分子纳米药物治疗骨肉瘤的相关研究报道。结果与结论:骨肉瘤是最常见的恶性骨肿瘤,主要影响儿童和青少年,早期远处肺转移和局部高侵袭性使骨肉瘤患者长期生存率降低。虽然化疗提高了骨肉瘤患者的生存率,但其应用潜力因严重不良反应和耐药性受到限制。与传统化疗相比,高分子纳米药物不仅降低了对正常组织的毒副作用,而且还能够延长体内循环时间,使化疗药物在肿瘤部位持续缓慢释放,从而提高了治疗效果。因此高分子纳米药物对于骨肉瘤的治疗具有巨大的应用前景。
基金supported by the Vanke Special Fund for Public Health and Health Discipline Development,Tsinghua University(2022Z82WKJ005,2022Z82WKJ013)the Tsinghua University Spring Breeze Fund(2021Z99CFZ007)+2 种基金the National Natural Science Foundation of China(22175107)Funding by Tsinghua Universitythe Starry Night Science Fund of Zhejiang University Shanghai Institute for Advanced Study(SN-ZJU-SIAS-006)。
文摘The clinical translation of nanomedicines has been strongly hampered by the limitations of delivery vehicles,promoting scientists to search for novel nanocarriers.Although cell membrane-based delivery systems have attracted extensive attention,further functionalizations are urgently desired to augment their theranostic functions.We propose a cell-friendly supramolecular strategy to engineer cell membranes utilizing cyclodextrin-based host–guest molecular recognitions to fix the defects arising from chemical and genetic modifcations.In this study,the supramolecular cell membrane vesicles(SCMVs)specifcally accumulate in tumors,benefting from tumor-homing capability and the enhanced permeability and retention effect.SCMVs co-delivering indocyanine green and an indoleamine 2,3-dioxygenase inhibitor effectively ablate tumors combining photodynamic therapy and immunotherapy.Driven by host–guest inclusion complexation,SCMVs successfully encapsulate resiquimod to repolarize tumor-associated macrophages into M1 phenotype,synergizing with immune checkpoint blockade therapy.This supramolecular engineering methodology based on noncovalent interactions presents a generalizable and cell-friendly tactic to develop living cell–originated nanomaterials for precise cancer therapy.
基金National Natural Science Foundation of Chinagrant number:81172170,81371288+1 种基金Science and Technology Research and Development Program of Shanxi Provincegrant number:2013KW32-04
文摘Biodegradable polymeric nanoparticles are more and more frequently used in drug delivery systems, which represent one of the most rapidly developing areas. In our previous study, a novel natural hybrid polyester, polyethylene glycol 200 （PEG200） end-capped poly （3-hydroxybutyrate-co-3-hydroxyhcxanoate） （PHBHHx-PEG） was directly produced by Aeromonas hydrophila fermentation. In this study, the performance of the novel biodegradable PHBHHx-PEG copolyester as a sustained release carrier for hydrophobic drugs with different molecular weights and the in vitro sustained release profile were investigated. 5-Fluorouracil （5-Fu, Mw=130.1）, TGX221 （Mw=364.4）, and Rapamycin （RAP, Mw=914.2） were used as the model drugs. PHBHHx-PEG nanoparticles entrapped with 5-Fu, TGX221 and RAP were fabricated by a modified emulsification/solvent evaporation method, respectively. The average diameter of 5-Fu, TGX221, and RAP loaded PHBHHx-PEG nanoparticles was between 198.2-217.4 nm, and the entrapment efficiency of the three drugs was 62.5%, 93.4% and 91.9%, respectively. The in vitro release profiles of 5-Fu, TGX221 and RAP from PHBHHx-PEG nanoparticles were different. 5-Fu showed faster release rate and an obvious initial burst release phase. TGX221 and RAP were demonstrated to be released more slowly and steadily. The release percentages of 5-Fu, TGX221 and RAP were 97.7%, 85.1% and 74.7% after releasing for 72 h. PHBHHx-PEG is a kind of promising material as a carrier for the entrapment and delivery of hydrophobic drugs especially for those drugs with high molecular weight.
