Miot-Noirault Elisabeth, Vidal Aurélien, Morlieras Jessica, Bonazza Pauline, Auzeloux Philippe, Besse Sophie, Dauplat Marie-Mélanie, Peyrode Caroline, Degoul Françoise, Billotey Claire, Lux François, Rédini Françoise, Tillement Olivier, Chezal Jean-Michel, Kryza David, Janier Marc
UMR 990 INSERM, Université d'Auvergne, 63000 Clermont-Ferrand, France.
UMR 990 INSERM, Université d'Auvergne, 63000 Clermont-Ferrand, France.
Nanomedicine. 2014 Nov;10(8):1887-95. doi: 10.1016/j.nano.2014.06.011. Epub 2014 Jun 25.
This work takes place in the "cartilage targeting strategy", consisting in using the quaternary ammonium (QA) function as a vector to proteoglycans (PGs) of extracellular matrix (ECM). The objective was to demonstrate that QA could address gadolinium based small rigid platforms (SRP) to PG-rich tumors. SRP were functionalized with QA, radiolabeled with (111)Indium and evaluated for biodistribution in vivo, respectively to non functionalized SRP, in two experimental models: (i) the HEMCSS human xenograft model; (ii) the Swarm rat chondrosarcoma (SRC) orthotopic model. The contribution of cellular uptake to tumoral accumulation of nano-objects was also determined from in vitro binding. In the SRC model expressing a highly and homogeneously distributed PG content, tumor accumulation and retention of SRP@QA were increased by 40% as compared to non-functionalized SRP. When considering the radiosensitizing potential of gadolinium based SRP, these results provide hopes for the radiobiological approach of highly resistant tumor such as chondrosarcoma.
In this study, gadolinium-based complexing DOTA-surfaced small polysiloxane nanoparticles were functionalized with quaternary ammonium derivatives that target the extracellular matrix of chondrosarcoma. The authors demonstrate in a rat model that the use of these constructs results in a 40% increase of tumor accumulation and retention compared to non-functionalized (and otherwise same) platforms. Similar approaches would be welcome additions to the clinical armamentarium addressing chondrosarcoma.
本研究基于“软骨靶向策略”展开，该策略利用季铵（QA）官能团作为细胞外基质（ECM）中蛋白聚糖（PGs）的载体。目的是证明QA能够将基于钆的小型刚性平台（SRP）靶向富含PG的肿瘤。用QA对SRP进行功能化修饰，用（111）铟进行放射性标记，并分别在两种实验模型中评估其在体内的生物分布，以与未功能化的SRP进行比较：（i）HEMCSS人异种移植模型；（ii）群体大鼠软骨肉瘤（SRC）原位模型。还通过体外结合确定了细胞摄取对纳米物体肿瘤蓄积的贡献。在PG含量高度且均匀分布的SRC模型中，与未功能化的SRP相比，SRP@QA的肿瘤蓄积和滞留增加了40%。考虑到基于钆的SRP的放射增敏潜力，这些结果为软骨肉瘤等高度耐药肿瘤的放射生物学治疗带来了希望。
在本研究中，基于钆的络合DOTA表面的小型聚硅氧烷纳米颗粒用靶向软骨肉瘤细胞外基质的季铵衍生物进行功能化修饰。作者在大鼠模型中证明，与未功能化（其他方面相同）的平台相比，使用这些构建体可使肿瘤蓄积和滞留增加40%。类似的方法将是治疗软骨肉瘤的临床手段中的受欢迎补充。
