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首页> 外文期刊>Cancer letters >Selective biophysical interactions of surface modified nanoparticles with cancer cell lipids improve tumor targeting and gene therapy
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Selective biophysical interactions of surface modified nanoparticles with cancer cell lipids improve tumor targeting and gene therapy

机译：表面修饰的纳米粒子与癌细胞脂质的选择性生物物理相互作用改善了肿瘤靶向和基因治疗

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Targeting gene- or drug-loaded nanoparticles (NPs) to tumors and ensuring their intratumoral retention after systemic administration remain key challenges to improving the efficacy of NP-based therapeutics. Here, we investigate a novel targeting approach that exploits changes in lipid metabolism and cell membrane biophysics that occur during malignancy. We hypothesized that modifications to the surface of NPs that preferentially increase their biophysical interaction with the membrane lipids of cancer cells will improve intratumoral retention and in vivo efficacy upon delivery of NPs loaded with a therapeutic gene. We have demonstrated that different surfactants, incorporated onto the NPs' surface, affect the biophysical interactions of NPs with the lipids of cancer cells and normal endothelial cells. NPs surface modified with didodecyldimethylammoniumbromide (DMAB) demonstrated greater interaction with cancer cell lipids, which was 6.7-fold greater than with unmodified NPs and 5.5-fold greater than with endothelial cell lipids. This correlated with increased uptake of DMAB-modified NPs with incubation time by cancer cells compared to other formulations of NPs and to uptake by endothelial cells. Upon systemic injection, DMAB-NPs demonstrated a 4.6-fold increase in tumor accumulation compared to unmodified NPs which also correlated to improved efficacy of p53 gene therapy. Characterization of the biophysical interactions between NPs and lipid membranes of tumors or other diseased tissues/organs may hold promise for engineering targeted delivery of therapeutics.
机译：将负载基因或药物的纳米颗粒（NPs）靶向肿瘤并确保其在全身性给药后在肿瘤内的保留仍然是提高基于NP的治疗剂疗效的关键挑战。在这里，我们研究了一种新颖的靶向方法，该方法利用了在恶性肿瘤期间发生的脂质代谢和细胞膜生物物理变化。我们假设对NP表面进行修饰，优先增加其与癌细胞膜脂的生物物理相互作用，这将改善肿瘤内滞留性和递送载有治疗基因的NP后的体内功效。我们已经证明，结合到NPs表面的不同表面活性剂会影响NPs与癌细胞和正常内皮细胞脂质的生物物理相互作用。经十二烷基二甲基溴化铵（DMAB）表面修饰的NPs与癌细胞脂质的相互作用更大，比未修饰的NPs高6.7倍，比内皮细胞脂质高5.5倍。与其他NP制剂相比，这与癌细胞温育时间增加了对DMAB修饰的NP的摄取以及内皮细胞的摄取有关。全身注射后，与未修饰的NPs相比，DMAB-NPs的肿瘤蓄积增加了4.6倍，这也与p53基因治疗的疗效提高相关。 NP或肿瘤或其他患病组织/器官的脂膜之间的生物物理相互作用的表征可能为工程靶向治疗提供前景。

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