Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, India.
Sci Rep. 2018 Feb 8;8(1):2624. doi: 10.1038/s41598-018-21084-8.
Recently, liposomes-microbubble conjugates have emerged as a promising ultrasound (US)-responsive platform for cancer therapeutics. However, these are limited by their size in terms of tumor penetration. Additionally, there have been no attempts to enhance the smartness of such conjugates which have been used only as passive carriers. The present study explores submicron sized (756 ± 180.0 nm), US-responsive, phosphatidylserine (PS)-based paclitaxel-liposomes-nanobubble conjugates (PSPLBC) with an additional pro-apoptotic effect towards enhanced anti-cancer efficacy and image-guidance. The developed PSPLBC underwent cavitation in response to US-trigger, exhibiting in vitro pulsatile release with a 10-fold increase in cellular internalization as compared to control. The PS-containing formulations were found to be pro-apoptotic and exhibited strong synergism between PS and paclitaxel (Combination Index, CI < 0.1). This resulted in significantly high anti-tumor efficacy both in vitro and in vivo conditions (98.3 ± 0.8% tumor growth inhibition, TGI). Significant reduction in tumor proliferation index and MVD, as well as significant increase in apoptosis, were observed for the treated tumor sections. Further, the intravenous (i.v.) administration of PSPLBC enhanced the tumor US-contrast by 2-fold as compared to SonoVue. These results, show the potential of PSPLBC as a promising non-invasive, pro-apoptotic, smart DDS for US-responsive, image-guided cancer therapeutics.
近年来，脂质体-微泡缀合物已成为一种很有前途的超声（US）响应平台，可用于癌症治疗。然而，这些载体在肿瘤穿透方面受到其大小的限制。此外，目前还没有人试图增强这些缀合物的智能性，因为它们仅被用作被动载体。本研究探索了亚微米大小（756±180.0nm）、超声响应、基于磷脂酰丝氨酸（PS）的紫杉醇脂质体-纳米泡缀合物（PSPLBC），具有额外的促凋亡作用，以增强抗癌疗效和图像引导。所开发的 PSPLBC 在超声触发下发生空化，表现出体外脉动释放，与对照相比，细胞内化增加了 10 倍。含有 PS 的制剂被发现具有促凋亡作用，并表现出 PS 和紫杉醇之间的强烈协同作用（组合指数，CI<0.1）。这导致体外和体内条件下的抗肿瘤疗效显著提高（肿瘤生长抑制率 98.3±0.8%，TGI）。处理过的肿瘤切片中观察到肿瘤增殖指数和 MVD 的显著降低，以及凋亡的显著增加。此外，与 SonoVue 相比，PSPLBC 的静脉内（i.v.）给药使肿瘤 US 对比增强了 2 倍。这些结果表明，PSPLBC 作为一种有前途的非侵入性、促凋亡、智能 DDS，可用于超声响应、图像引导的癌症治疗。
