Treatment of pancreatic ductal adenocarcinoma with tumor antigen specific-targeted delivery of paclitaxel loaded PLGA nanoparticles.
Treatment of pancreatic ductal adenocarcinoma with tumor antigen specific-targeted delivery of paclitaxel loaded PLGA nanoparticles.
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DOI：
10.1186/s12885-018-4393-7
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发表时间：
2018-04-23
期刊：
影响因子：
3.8
通讯作者：
Mukherjee P
中科院分区：
文献类型：
--
作者：
Wu ST;Fowler AJ;Garmon CB;Fessler AB;Ogle JD;Grover KR;Allen BC;Williams CD;Zhou R;Yazdanifar M;Ogle CA;Mukherjee P
胰腺导管腺癌（PDA）仍然是最具侵袭性的癌症，5年生存率低于10%。化疗药物全身给药对PDA患者有严重的副作用，不能显著提高总生存率。非常期望通过靶向化疗药物的递送并增加其在肿瘤部位的积累来提高化疗药物的治疗功效。MUC 1是一种膜系糖蛋白，在> 80%的PDA中异常过表达，因此使其成为有吸引力的抗原靶标。将与肿瘤特异性MUC 1抗体TAB 004缀合的聚乳酸-共-乙醇酸纳米颗粒（PLGA NPs）用作纳米载体，用于体外靶向递送到人PDA细胞系中和体内靶向递送到PDA肿瘤中。PLGA NP装载有荧光成像剂，荧光素二乙酸酯（FDA）和尼罗红（NR）或异氰绿绿色（ICG），分别用于体外和体内成像，或装载有化疗药物紫杉醇（PTX），用于体外细胞毒性测定。使用共聚焦显微镜观察纳米载体在具有高和低MUC 1表达的PDA细胞中的体外内化。使用体内成像系统（IVIS）来可视化纳米载体的体内肿瘤靶向。使用MTT（3-（4，5-二甲基噻唑-2-基）-2，5-二苯基四唑溴化物）测定来确定用装载PTX的纳米载体处理的细胞的体外细胞存活。单侧t检验比较各浓度下的处理组，双因素ANOVA比较抗体和PLGA纳米颗粒的内化。在体外，TAB 004缀合的ICG纳米载体在PDA细胞中的内化显著优于其非缀合的对应物。类似地，TAB 004缀合的PTX纳米载体在体外对PDA细胞的细胞毒性显著高于其非缀合的对应物。在体内，与未结合的纳米载体相比，TAB 004结合的ICG纳米载体在PDA肿瘤中的蓄积增加，同时保留正常器官。该研究为未来开发新型MUC 1靶向纳米载体提供了有希望的数据，用于将成像剂或药物直接递送到肿瘤微环境中。本文的在线版本（10.1186/s12885-018-4393-7）包含补充材料，可供授权用户使用。
Pancreatic ductal adenocarcinoma (PDA) remains the most aggressive cancers with a 5-year survival below 10%. Systemic delivery of chemotherapy drugs has severe side effects in patients with PDA and does not significantly improve overall survival rate. It is highly desirable to advance the therapeutic efficacy of chemotherapeutic drugs by targeting their delivery and increasing accumulation at the tumor site. MUC1 is a membrane-tethered glycoprotein that is aberrantly overexpressed in > 80% of PDA thus making it an attractive antigenic target. Poly lactic-co-glycolic acid nanoparticles (PLGA NPs) conjugated to a tumor specific MUC1 antibody, TAB004, was used as a nanocarrier for targeted delivery into human PDA cell lines in vitro and in PDA tumors in vivo. The PLGA NPs were loaded with fluorescent imaging agents, fluorescein diacetate (FDA) and Nile Red (NR) or isocyanine green (ICG) for in vitro and in vivo imaging respectively or with a chemotherapeutic drug, paclitaxel (PTX) for in vitro cytotoxicity assays. Confocal microscopy was used to visualize internalization of the nanocarrier in vitro in PDA cells with high and low MUC1 expression. The in vivo imaging system (IVIS) was used to visualize in vivo tumor targeting of the nanocarrier. MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay was used to determine in vitro cell survival of cells treated with PTX-loaded nanocarrier. One-sided t-test comparing treatment groups at each concentration and two-way ANOVAs comparing internalization of antibody and PLGA nanoparticles. In vitro, TAB004-conjugated ICG-nanocarriers were significantly better at internalizing in PDA cells than its non-conjugated counterpart. Similarly, TAB004-conjugated PTX-nanocarriers were significantly more cytotoxic in vitro against PDA cells than its non-conjugated counterpart. In vivo, TAB004-conjugated ICG-nanocarriers showed increased accumulation in the PDA tumor compared to the non-conjugated nanocarrier while sparing normal organs. The study provides promising data for future development of a novel MUC1-targeted nanocarrier for direct delivery of imaging agents or drugs into the tumor microenvironment. The online version of this article (10.1186/s12885-018-4393-7) contains supplementary material, which is available to authorized users.
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DOI：
10.1016/j.bbrc.2009.08.059
发表时间：
2009-10-30
影响因子：
3.1
作者：
Hisatsune, Akinori;Kawasaki, Mitsuru;Kim, Kwang Chul
通讯作者：
Kim, Kwang Chul
影响因子：
2.9
作者：
Dréau D;Moore LJ;Alvarez-Berrios MP;Tarannum M;Mukherjee P;Vivero-Escoto JL
通讯作者：
Vivero-Escoto JL
DOI：
10.1016/j.jconrel.2013.06.039
发表时间：
2013-11-28
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Hollis CP;Weiss HL;Leggas M;Evers BM;Gemeinhart RA;Li T
通讯作者：
Li T
影响因子：
10.8
作者：
Fonseca, C;Simoes, S;Gaspar, R
通讯作者：
Gaspar, R
影响因子：
11.2
作者：
Kamphorst JJ;Nofal M;Commisso C;Hackett SR;Lu W;Grabocka E;Vander Heiden MG;Miller G;Drebin JA;Bar-Sagi D;Thompson CB;Rabinowitz JD
通讯作者：
Rabinowitz JD