具有肿瘤靶向递送和光触发肽药物释放的DNA水凝胶基纳米复合物,用于肿瘤特异性治疗。
DNA Hydrogel-Based Nanocomplexes with Cancer-Targeted Delivery and Light-Triggered Peptide Drug Release for Cancer-Specific Therapeutics.
发表日期:2023 Mar 31
作者:
Mohzibudin Z Quazi, Nokyoung Park
来源:
BIOMACROMOLECULES
摘要:
基于化疗药物递送的癌症治疗已经得到最大程度的研究;最近,由于与其他合成药物相比较少的免疫原性和更低的生产成本,肽类药物已经成为抗癌药物。然而,仍然存在这些化疗药物对健康组织的副作用是一个需要处理的重大问题,这些副作用通常是由于没有定位的传递和意外泄漏造成的。此外,在传递过程中,肽类药物易于被酶攻击而被降解。为了解决这些问题,我们研制了一种稳健的、针对癌症的肽类药物递送系统,其在体外具有微不足道的细胞毒性。通过在纳米尺度的DNA水凝胶(Dgel)上逐步功能化,构建了一个肽类药物递送载体(Dgel-PD-AuNP-YNGRT)。通过静电吸引,负载了穿透细胞壁的抗癌肽药物Buforin IIb在Dgel网络内部,并通过AuNP组装而实现。这些AuNP作为光热反应剂,用于光触发的肽类药物释放。此外,一种癌细胞定向递送的肽也被绑定在Dgel上。经过用癌细胞和正常细胞进行的研究,发现Dgel-PD-AuNP-YNGRT纳米复合物可以特异性地递送至癌细胞,并通过光刺激激活,释放抗癌肽药物以杀死癌细胞,并且对正常细胞系没有明显的有害影响。通过细胞存活率实验得出的结果显示,在高强度(15 W/cm2)的光热触发释放下,肽药物的杀伤能力比仅肽药物治疗提高了44%。同样,Bradford分析表明,通过我们设计的Dgel-PD-AuNP-YNGRT纳米复合物,肽类药物的释放率可以高达90%。Dgel-PD-AuNP-YNGRT纳米复合物可能是一种理想的抗癌肽药物递送平台,可以实现安全、特异性的癌症靶向和高效的肽类药物递送。
Cancer therapies based on chemotherapeutic drug delive ries have been the most facilitated studies. Recently, peptide drugs have emerged as anticancer drugs due to their less immunogenicity and lower production costs compared with other synthetics. However, still, the side effects of these chemotherapeutics on healthy tissues have been a great concern to deal with, and these side effects are usually caused by off-targeted delivery and unwanted leakage. In addition, peptides are easily degraded by enzyme attacks during delivery. To address these concerns, here, we developed a robust, cancer-specific peptide drug delivery system with negligible cytotoxicity in in vitro. A peptide drug delivery vehicle (Dgel-PD-AuNP-YNGRT) was constructed by stepwise functionalization on a nanoscale DNA hydrogel (Dgel). A cell-penetrating anticancer peptide drug, Buforin IIb, was loaded within the Dgel network via electrostatic attraction followed by AuNP assembly. The AuNPs were employed as photothermal reagents for light-triggered peptide drug release. An additional peptide, including a cancer-targeting YNGRT sequence, was also bound on the Dgel for cancer-cell-targeted delivery. According to the results obtained from the studies employing cancer cells as well as normal cells, Dgel-PD-AuNP-YNGRT nanocomplexes could be delivered specifically to cancer cells, activated by light illumination, and release anticancer peptide drugs to kill cancer cells with no cytotoxicity and negligible hazardous effect on normal cell lines. The obtained cell viability assay suggests that at a high intensity (15 W/cm2), photothermally triggered released peptide drug has shown up to 44% higher kill than only peptide drug treatments in cancer cells. Similarly, the Bradford assay demonstrated that up to 90% of peptide drugs were released with our engineered Dgel-PD-AuNP-YNGRT nanocomplex. The Dgel-PD-AuNP-YNGRT nanocomplex may serve as an ideal anticancer peptide drug delivery platform for safe, cancer-specific targeting and efficient peptide drug delivery in cancer therapy.