In vivo biodistribution and toxicity of intravesical administration of quantum dots for optical molecular imaging of bladder cancer.
In vivo biodistribution and toxicity of intravesical administration of quantum dots for optical molecular imaging of bladder cancer.
复制标题
体内生物分布和静脉内施用量子点的毒性，用于膀胱癌的光学分子成像。
DOI：
10.1038/s41598-017-08591-w
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发表时间：
2017-08-24
影响因子：
4.6
通讯作者：
Liao JC
中科院分区：
文献类型：
--
作者：
Pan Y;Chang T;Marcq G;Liu C;Kiss B;Rouse R;Mach KE;Cheng Z;Liao JC
光学分子成像具有改善癌症诊断的潜力。与有机染料相比，诸如量子点（QD）的荧光纳米颗粒提供了上级光学特性，但是它们的体内应用受到来自全身给药的潜在毒性的限制。局部给药为靶向纳米颗粒提供了一种有吸引力的途径，可以最大限度地减少暴露和减少剂量。以前，我们证明了成功的离体内窥镜成像的人膀胱癌局部（即膀胱内）管理的量子点结合的抗CD 47。在此，我们研究了膀胱内滴注的游离QD和抗CD 47-QD在小鼠中的体内生物分布和毒性。采用电感耦合等离子体质谱法评估抗CD 47-QD的体内生物分布。使用血液检查、器官重量和组织学评估局部和全身毒性。平均而言，QD在膀胱外无显著蓄积，但在一些小鼠中，我们检测到QD的膀胱外生物分布，表明在某些条件下存在全身暴露途径。滴注后7天内无急性毒性迹象。靶向纳米颗粒的膀胱内给药可以减少全身暴露，但对于临床使用，应使用具有既定生物安全性特征的纳米颗粒，以减少发生全身暴露的情况下的长期毒性。
Optical molecular imaging holds the potential to improve cancer diagnosis. Fluorescent nanoparticles such as quantum dots (QD) offer superior optical characteristics compared to organic dyes, but their in vivo application is limited by potential toxicity from systemic administration. Topical administration provides an attractive route for targeted nanoparticles with the possibility of minimizing exposure and reduced dose. Previously, we demonstrated successful ex vivo endoscopic imaging of human bladder cancer by topical (i.e. intravesical) administration of QD-conjugated anti-CD47. Herein we investigate in vivo biodistribution and toxicity of intravesically instilled free QD and anti-CD47-QD in mice. In vivo biodistribution of anti-CD47-QD was assessed with inductively coupled plasma mass spectrometry. Local and systemic toxicity was assessed using blood tests, organ weights, and histology. On average, there was no significant accumulation of QD outside of the bladder, although in some mice we detected extravesical biodistribution of QD suggesting a route for systemic exposure under some conditions. There were no indications of acute toxicity up to 7 days after instillation. Intravesical administration of targeted nanoparticles can reduce systemic exposure, but for clinical use, nanoparticles with established biosafety profiles should be used to decrease long-term toxicity in cases where systemic exposure occurs.
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影响因子：
3.7
作者：
Liu J;Wang L;Zhao F;Tseng S;Narayanan C;Shura L;Willingham S;Howard M;Prohaska S;Volkmer J;Chao M;Weissman IL;Majeti R
通讯作者：
Majeti R
影响因子：
6.4
作者：
Johnson, JR;Brown, JJ
通讯作者：
Brown, JJ
影响因子：
4.6
作者：
Ang, Wei Xia;Zhao, Ying;Wang, Shu
通讯作者：
Wang, Shu
影响因子：
15.3
作者：
Daneshmand, Siamak;Schuckman, Anne K.;Steinberg, Gary D.
通讯作者：
Steinberg, Gary D.
DOI：
10.1146/annurev-anchem-060908-155136
发表时间：
2013
期刊：
Annual review of analytical chemistry (Palo Alto, Calif.)
影响因子：
--
作者：
Kairdolf BA;Smith AM;Stokes TH;Wang MD;Young AN;Nie S
通讯作者：
Nie S