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Tumor-targeted/reduction-triggered composite multifunctional nanoparticles for breast cancer chemo-photothermal combinational therapy

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Acta Pharmaceutica Sinica B 2022年第6期12卷 2710-2730页

作者： Yun Yang Danrong Hu Yi Lu bingyang chu Xinlong He Yu Chen Yao Xiao Chengli Yang Kai Zhou Liping Yuan Zhiyong Qian State Key Laboratory of Biotherapy and Cancer Center West China HospitalSichuan UniversityCollaborative Innovation Center of BiotherapyChengdu 610041China West China School of Pharmacy Sichuan UniversityChengdu 610041China

Breast cancer has become the most commonly diagnosed cancer type in the world.A combination of chemotherapy and photothermal therapy(PTT) has emerged as a promising strategy for breast cancer therapy.However,the intricacy of precise delivery and the ability to initiate drug release in specific tumor sites remains a challenging puzzle.Therefore,to ensure that the therapeutic agents are synchronously delivered to the tumor site for their synergistic effect,a multifunctional nanoparticle system(PCRHNs) is developed,which is grafted onto the prussian blue nanoparticles(PB NPs) by reductionresponsive camptothecin(CPT) prodrug copolymer,and then modified with tumor-targeting peptide cyclo(Asp-D-Phe-Lys-Arg-Gly)(cRGD) and hyaluronic acid(HA).PCRHNs exhibited nano-sized structure with good monodispersity,high load efficiency of CPT,triggered CPT release in response to reduction environment,and excellent photothermal conversion under laser irradiation.Furthermore,PCRHNs can act as a photoacoustic imaging contrast agent-guided PTT.In vivo studies indicate that PCRHNs exhibited excellent bio compatibility,prolonged blood circulation,enhanced tumor accumulation,allow tumor-specific che mo-photo thermal therapy to achieve synergistic antitumor effects with reduced systemic toxicity.Moreover,hyperthermia-induced upregulation of heat shock protein 70 in the tumor cells could be inhibited by CPT.Collectively,PCRHNs may be a promising therapeutic way for breast cancer therapy.

关键词： Breast cancer Chem-photothermal combinational therapy Camptothecin Prussian blue nanoparticles Reduction-responsive prodrugs

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Macrophage Membrane-Camouflaged shRNA and Doxorubicin:A pH-Dependent Release System for Melanoma Chemo-Immunotherapy

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Research 2022年第2期2022卷 161-178页

作者： Chengli Yang Yang Ming Kai Zhou Ying Hao Danrong Hu bingyang chu Xinlong He Yun Yang Zhiyong Qian State Key Laboratory of Biotherapy and Cancer Center West China HospitalSichuan Universityand Collaborative Innovation Center of BiotherapyChengduSichuan 610041China Departiment of Pharmacy The Affiliated Hospital of Guizhon Medical UniversityGuiyangGuizhou 550000China

mproving the eficacy of melanoma treatment remains an important global challenge.Here,we combined chemotherapy with protein tyrosine phosphatase nonreceptor type 2(Ptpn2)based immunotherapy in an effort to address this challenge.Shorthairpin RNA(shRNA)targeting Ptpn2 was coencapsulated with doxorubicin(DOX)in the cell membrane of MI macrophages(MIHD@RPR).The prepared nanoparticles(NPs)were effectively phagocytosed by B16F10 cells and MI macrophages,but not by MOmacrophages.Hence,NPevasion from the reticuloendothelial system(RES)was improved and NPenrichment in tumor sites increased.MIHD@RPR can directly kill tumor cells and stimulate immunogenic cell death(ICD)by DOX and downregulate Ptpn2.It can promote Ml macrophage polarization and dendritic cell maturation and increase the proportion of CD8+T cells.MIHD@RPR killed and inhibited the growth of primary melanoma and lung metastatic tumor celis without harming the surrounding tssue.These findings establish MIHD@RPR as a safe multifunctional nanoparticle capable of effectively combining chemotherapy and gene immunotherapies against melanoma.

关键词： chemotherapy inhibited melanoma

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Biomineralized polymer matrix composites for bone tissue repair:a review

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Science China Chemistry 2018年第12期61卷 1553-1567页

作者： Lin Zhong Ying Qu Kun Shi bingyang chu Minyi Lei Kangkang Huang Yingchun Gu Zhiyong Qian State Key Laboratory of Biotherapy and Cancer Center West China Hospital West China Medical School Sichuan University Department of Textile Engineering College of Light Industry & Textile & Food Engineering Sichuan University

Bone defects caused by trauma, infection or bone tumor resection, are highly prevalent. A small number(5%–10%) of these injuries fail to heal due to non-union and require surgical intervention. Currently, the principal treatment options for these defects are autografts, allografts, xenografts or synthetic grafts. The main problems associated with these therapies include pain,infection and donor site morbidity. Bone tissue engineering is a diverse field that focuses on the regeneration of bone by combining cells, scaffolds, growth factors and dynamic forces. There have been many recent studies utilizing biomineralized polymer matrix composites which mimic the natural structure of bone. The principal focus of this review is on recent advances in the synthesis of various types of biomineralized polymer matrix composite. Examples of the biomineralization of naturallyderived and synthetic polymers widely used for bone engineering are also summarized.

关键词： bomineralization natural-based materials synthetic polymers bone engineering

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Camptothecin@HMSNs/thermosensitive hydrogel composite for applications in preventing local breast cancer recurrence

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Chinese Chemical Letters 2018年第12期29卷 1819-1823页

作者： Jing Wu Ying Qu Kun Shi bingyang chu Yanpeng Jia Xue Xiao Qianjun He Zhiyong Qian Department of Hematology and Research Laboratory of Hematology State Key Laboratory of BiotherapyWest China HospitalSichuan University and Collaborative Innovation Center Department of Gynecology and Obstetrics West China Second University HospitalSichuan University Key Laboratory of Birth Defects and Related Diseases of Women and Children Sichuan UniversityMinistry of Education National-Regional Key Technology Engineering Laboratory for Medical Ultrasound Guangdong Key Laboratory for Biomedical Measurements and Ultrasound ImagingSchool of Biomedical EngineeringShenzhen University

Camptothecin has a strong tumor killing ability for a variety of tumor cells with its special anti-cancer mechanism including the breast cancer. However, because of its infinite hydrophobic property, its clinical application has been greatly limited. Early prevention of loco regional recurrence for the breast cancer is critical for patients who have undergone breast-conserving therapy. In the study,CPT was used for the inhibition of the recurrence after the operation. The hollow mesoporous silica nanoparticles were used as the carrier to improve the hydrophilic property and increase its bioavailability with the high loading capacity. The ability of the cellular uptake and antitumor activity was increased. Hydrogel was the ideal carrier for local therapy, so the CPT@HMSNs were loaded into the PLEL thermo sensitive hydrogel to be injected into the tumor sites after the tumor was resected. The recurrence was reduced in the group of CPT-HMSNs-PLEL and the side effect of CPT was decreased. They exhibit distinguished potential as drug carrier for local delivery.

关键词： Camptothecin Hollow mesoporous silica nanoparticles Breast cancer recurrence Thermosensitive hydrogel Local delivery

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Spatiotemporal variation and driving factors of water yield services on the Qingzang Plateau

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Geography and Sustainability 2021年第1期2卷 31-39页

作者： Xiaofeng Wang bingyang chu Xiaoming Feng Yuehao Li Bojie Fu Shirong Liu Jiming Jin College of Land Engineering Chang’an UniversityXi’an 710054China Shaanxi Provincial Key Laboratory of Land Engineering Xi’an 710054China National key laboratory of urban and regional ecology Chinese academy of sciencesBeijing 100085China Institute of land surface system science and sustainable development Beijing normal universityBeijing 100875China Key Laboratory of Forest Ecology and Environment China’s National Forestry and Grassland AdministrationInstitute of Forest EcologyEnvironment and ProtectionChinese Academy of ForestryNo.2 DongxiaofuHaidian DistrictBeijing 100091China Department of Watershed Sciences Utah State UniversityLoganUT 84322USA

Water resources are a basic need for social sustainable development and human existence.As an important national strategy for water resources security,spatial and temporal patterns and driving mechanisms of water yield ecosystem services on the Qingzang Plateau(QP)are critical for water resources management,optimal water allocation and the improvement of ecological water protection efficiency.However,only a few relevant studies are currently available.In this study,we simulated the water yield(WY)of the QP over 34 years,from 1982 to 2015,using the InVEST model and analyzed the spatiotemporal dynamic relationships between WY and climate change as well as between WY and vegetation change,using geographically weighted regression(GWR)models.The results showed that:1)from 1982 to 2015,the WY of the QP increased at an average rate of 3.8 mm/yr;2)WY presented a reduced spatial pattern from southeast to northwest;and 3)the WY driving factors have individual and spatial differences.In terms of the area percentage in promoting WY when analyzing each driving factor,precipitation(99.8%)and air pressure(53.3%)played the major roles in promoting WY,while temperature(71.9%),wind speed(57.2%),net primary productivity(87.2%),radiation(68.3%)and lake(87.7%)played negative roles.The areas where WY are dominated by temperature are the largest(41.1%),and followed by areas dominated by pressure(19.7%)and precipitation(18.5%).The results of this study provide scientific support for formulating regional water resources policy,social and economic development planning and other macro decisions for the QP.

关键词： Qingzang Plateau Water yield GWR models

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Melphalan-loaded methoxy poly(ethylene glycol)-poly(D,L-lactide)copolymer nanomicelles in the treatment of multiple myeloma

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中国化学快报:英文版 2023年第9期34卷 193-198页

作者： Yingying Chen Qiang Zeng bingyang chu Zhigang Liu Xue Wei Mengran Chen Peipei Yang Minghai Tang Ting Niu Yongqian Jia Ying Qu Zhiyong Qian Department of Hematology and Institute of Hematology State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China

Multiple myeloma(MM)is the second most common hematological tumor characterized by the proliferation of monoclonal plasma cells.Melphalan(MEL)is commonly used in the treatment of MM and is especially essential for patients undergoing autologous stem cell transplantation(ASCT).Although many drugs for MM have been developed in recent years,chemotherapy followed by ASCT remains the optimal option.Melphalan,the backbone of the conditioning regimen,brings severe toxicities at a high dose.Nanodrug delivery systems enable drugs to be highly effective and have low toxicity.In this study,methoxy poly(ethylene glycol)-poly(D,L-lactide)copolymer(MPEG-PDLLA)was chosen to encapsulate melphalan,and the characteristics,effectiveness,and safety of MEL/MPEG-PDLLA in vitro and in vivo were investigated.MEL/MPEG-PDLLA showed slow release and was easily engulfed by MM cells despite a result of the antitumor assay comparable to that of free melphalan in vitro.The in vivo results showed that MEL/MPEG-PDLLA could significantly alleviate tumor burden and prolong survival time without increasing the toxicity to vital organs.In addition,MEL/MPEG-PDLLA could significantly reduce the damage to the intestinal mucosa caused by melphalan.In conclusion,MEL/MPEG-PDLLA shows improved antitumor activity and has the potential to alleviate pains of MM patients undergoing ASCT.

关键词： Melphalan Multiple myeloma MPEG-PDLLA Nanomicelle

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青藏高原生态屏障生态系统时空演变及驱动机制

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生态学报 2022年第21期42卷 8581-8593页

作者：李月皓王晓峰楚冰洋牛泽鹏符鑫鑫延雨长安大学土地工程学院西安710054 陕西省土地工程重点实验室西安710054 长安大学地球科学与资源学院西安710054

青藏高原生态屏障是我国生态安全战略格局的重要组成部分,对我国乃至亚洲生态安全具有重要的屏障作用。研究青藏高原生态屏障生态格局的演变规律,探究影响生态系统变化的驱动机制,对青藏高原生态屏障建设和保障国家生态安全具有重要的... 详细信息

青藏高原生态屏障是我国生态安全战略格局的重要组成部分,对我国乃至亚洲生态安全具有重要的屏障作用。研究青藏高原生态屏障生态格局的演变规律,探究影响生态系统变化的驱动机制,对青藏高原生态屏障建设和保障国家生态安全具有重要的意义。利用多源遥感数据,分析了2000—2015年国家屏障区生态格局演变规律,选取了自然和社会经济等驱动要素,采用冗余分析等方法解析了青藏高原生态屏障生态系统演变机制。结果表明:(1)2000—2015年间,青藏高原生态屏障生态系统格局发生明显变化,草地生态系统减少了1792 km^(2),主要转化为荒漠生态系统和河流生态系统,转换面积分别为1088 km^(2)和832 km^(2);河流生态系统增加了1600 km^(2),主要由荒漠生态系统和草地生态系统转换而来,分别转换了1152 km^(2)和832 km^(2)。(2)2000—2015年青藏高原生态屏障生态系统格局演变驱动机制中以社会经济因子为主。冗余分析结果显示国内生产总值(83%)和人口数量(72%)贡献率最大;方差分析结果中国内生产总值和人口数量的共同贡献率达到了77%;地理加权回归结果显示生态系统演变受社会经济因子主导的区域面积比例为60.41%。(3)青藏高原生态屏障内人口数量的总贡献率达到了72%,在人口数量作用下生态系统呈正向转换的面积占比达到了86.24%,且人口数量与河流、森林生态系统的相关程度较高,综合说明了青藏高原生态屏障内生态保护政策的实施、生态工程的建设卓有成效。

关键词：青藏高原生态屏障生态系统时空演变驱动机制

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生物沥浸含锰烟粉尘中的锰及其浸出机理研究

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环境污染与防治 2023年第2期45卷 151-156页

作者：崔延超田炳阳贾纯友褚会超王佳辛宝平北京建筑大学环境与能源工程学院北京100044 北京理工大学材料学院北京100081

含锰烟粉尘是钢铁行业产生的一类含有锰、锌、铅和硅等元素的工业固废,既存在一定的环境风险,又具有潜在的资源回收价值。对含锰烟粉尘分别用生物酸和无机酸进行沥浸,分析锰的浸出机理,进一步通过响应面法确定生物酸沥浸锰的最佳工艺条... 详细信息

含锰烟粉尘是钢铁行业产生的一类含有锰、锌、铅和硅等元素的工业固废,既存在一定的环境风险,又具有潜在的资源回收价值。对含锰烟粉尘分别用生物酸和无机酸进行沥浸,分析锰的浸出机理,进一步通过响应面法确定生物酸沥浸锰的最佳工艺条件。结果表明,锰的浸出机理为酸溶和生物酸还原的复合机理,生物酸中的还原性物质和沥浸过程中产生的Fe^(2+)能够将高价锰还原为Mn^(2+),使生物酸体系锰的浸出率比无机酸体系高。生物酸浸出锰的最佳工艺条件:固液比为1.22 g∶100 mL,初始pH为0.81,温度为29.14℃,转速为152.29 r/min,此条件下实际锰浸出率为76.51%。

关键词：生物沥浸含锰烟粉尘机理分析响应面优化浸出率

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脑积水易被忽略的原因:Blake’s囊肿

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中国中西医结合影像学杂志 2023年第4期21卷 448-450页

作者：张鸣初迎幸卞冰阳山东省威海市妇幼保健院医学影像科山东威海264200 吉林大学第一医院放射线科吉林长春130021

目的:分析Blake’s囊肿所致脑积水的MRI表现,以提高临床对该病的诊断水平。方法:搜集30例Blake’s囊肿患者的临床资料,其中Blake’s囊肿所致脑积水11例(脑积水组),均出现嗜睡、呕吐、头痛、头晕等颅压增高表现;19例无脑积水(无脑积水组)... 详细信息

目的:分析Blake’s囊肿所致脑积水的MRI表现,以提高临床对该病的诊断水平。方法:搜集30例Blake’s囊肿患者的临床资料,其中Blake’s囊肿所致脑积水11例(脑积水组),均出现嗜睡、呕吐、头痛、头晕等颅压增高表现;19例无脑积水(无脑积水组)。30例均行MRI检查。结果:30例Blake’s囊肿MRI T2WI或T1WI正中矢状位均显示小脑后下方囊肿,并与扩张的第四脑室交通;小脑蚓部完整,但其下方有受压改变;T1WI或T2WI轴位示小脑半球间隙增宽,小脑幕及窦汇位置正常。11例伴中、重度脑积水,无室旁水肿,小脑蚓部腹侧最下缘切线与脑干背侧切线之间的夹角(BV角)(68±3)°,明显大于无脑积水患者。结论:Blake’s囊肿所致脑积水临床相对少见,易被忽略。MRI在Blake’s囊肿伴脑积水的诊断及鉴别诊断方面有明显优势,尤其是矢状位成像序列,应作为Blake’s囊肿首选的检查方法。

关键词： Blake’s囊肿磁共振检查脑积水

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化学—生物两段浸出锰烟尘中的锰

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环境污染与防治 2023年第6期45卷 791-795页

作者：崔延超田炳阳李志华褚会超王旭王佳辛宝平北京建筑大学环境与能源工程学院北京100044 北京理工大学材料学院北京100081

单一的化学沥浸或者生物沥浸达不到目标金属高效浸出的效果,所以需要考虑两种工艺结合的方式。第一段用化学酸对锰烟尘进行化学沥浸,然后第二段用生物酸对化学沥浸渣进行生物沥浸,对比原样和沥浸渣中锰的赋存形态和浸出液中锰的含量,得... 详细信息

单一的化学沥浸或者生物沥浸达不到目标金属高效浸出的效果,所以需要考虑两种工艺结合的方式。第一段用化学酸对锰烟尘进行化学沥浸,然后第二段用生物酸对化学沥浸渣进行生物沥浸,对比原样和沥浸渣中锰的赋存形态和浸出液中锰的含量,得到化学—生物沥浸的机理。结果表明:固液比10 g∶100 mL、pH 0.8、温度35℃、转速135 r/min的条件下,第一段化学沥浸锰的浸出率为67.36%;第二段生物沥浸锰的浸出率为22.45%,化学—生物两段整体锰浸出率为89.81%。

关键词：涉重危废锰烟尘化学沥浸生物沥浸两段浸出浸出率

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