■目前的免疫疗法具有意想不到的严重副作用和治疗阻力,并没有导致黑色素瘤患者的预期结果,需要发现更有效的药物。来自眼镜蛇毒液的细胞毒素(CTX)已被确定具有良好的细胞溶解活性和抗肿瘤功效,被认为是一种有前途的新型抗癌剂。然而,具有优异阴离子磷脂酰丝氨酸脂质结合能力的两亲性CTX也可能损害正常细胞。
■我们开发了具有高CTX载量(CTX@PSL)的pH响应性脂质体,用于肿瘤微环境中药物的靶向酸性刺激释放。形态学,尺寸,zeta电位,药物释放动力学,并对保存稳定性进行了表征。细胞摄取,促凋亡作用,使用MTT法和流式细胞术评估细胞毒性。最后,使用体内成像系统系统评估CTX@PSL的组织分布和抗肿瘤作用.
■CTX@PSL表现出高药物包封率,药物装载,稳定性,和在酸性条件下的快速释放曲线。这些纳米粒子,不规则球形,尺寸小,可以有效地在肿瘤部位积聚(比游离CTX高六倍),并迅速内化到癌细胞中(细胞摄取效率高2.5倍)。CTX@PSL显示出明显更强的细胞毒性(IC50为0.25μg/mL),并且比其他制剂中的细胞凋亡增加(凋亡率71.78±1.70%)。CTX@PSL的抑瘤效果明显优于游离CTX或常规脂质体(抑瘤率79.78±5.93%)。
■我们的结果表明,CTX@PSL改善了肿瘤位点的积累和细胞内的摄取,从而持续和靶向地释放CTX。通过结合CTX和刺激响应纳米技术的优势,新型CTX@PSL纳米制剂是癌症治疗的有希望的治疗候选药物.
UNASSIGNED: Current immunotherapies with unexpected severe side effects and treatment resistance have not resulted in the desired outcomes for patients with melanoma, and there is a need to discover more effective medications. Cytotoxin (CTX) from Cobra Venom has been established to have favorable cytolytic activity and antitumor efficacy and is regarded as a promising novel anticancer agent. However, amphiphilic CTX with excellent anionic phosphatidylserine lipid-binding ability may also damage normal cells.
UNASSIGNED: We developed pH-responsive liposomes with a high CTX load (CTX@PSL) for targeted acidic-stimuli release of drugs in the tumor microenvironment. The morphology, size, zeta potential, drug-release kinetics, and preservation stability were characterized. Cell uptake, apoptosis-promoting effects, and cytotoxicity were assessed using MTT assay and flow cytometry. Finally, the tissue distribution and antitumor effects of CTX@PSL were systematically assessed using an in vivo imaging system.
UNASSIGNED: CTX@PSL exhibited high drug entrapment efficiency, drug loading, stability, and a rapid release profile under acidic conditions. These nanoparticles, irregularly spherical in shape and small in size, can effectively accumulate at tumor sites (six times higher than free CTX) and are rapidly internalized into cancer cells (2.5-fold higher cell uptake efficiency). CTX@PSL displayed significantly stronger cytotoxicity (IC50 0.25 μg/mL) and increased apoptosis in than the other formulations (apoptosis rate 71.78±1.70%). CTX@PSL showed considerably better tumor inhibition efficacy than free CTX or conventional liposomes (tumor inhibition rate 79.78±5.93%).
UNASSIGNED: Our results suggest that CTX@PSL improves tumor-site accumulation and intracellular uptake for sustained and targeted CTX release. By combining the advantages of CTX and stimuli-responsive nanotechnology, the novel CTX@PSL nanoformulation is a promising therapeutic candidate for cancer treatment.