Innovative Targeting Group, Laboratory Experimental Surgical Oncology, Section Surgical Oncology, Department of Surgery, Erasmus Medical Center , Room Ee151b, PO Box 2040, 3000 CA Rotterdam , The Netherlands
Expert Opin Drug Deliv. 2014 Jan;11(1):83-100. doi: 10.1517/17425247.2014.866650. Epub 2013 Dec 10.
Currently available chemotherapy is hampered by a lack in tumor specificity and resulting toxicity. Small and long-circulating liposomes can preferentially deliver chemotherapeutic drugs to tumors upon extravasation from tumor vasculature. Although clinically used liposomal formulations demonstrated significant reduction in toxicity, enhancement of therapeutic activity has not fully met expectations.
Low drug bioavailability from liposomal formulations and limited tumor accumulation remain major challenges to further improve therapeutic activity of liposomal chemotherapy. The aim of this review is to highlight strategies addressing these challenges. A first strategy uses hyperthermia and thermosensitive liposomes to improve tumor accumulation and trigger liposomal drug bioavailability. Image-guidance can aid online monitoring of heat and drug delivery and further personalize the treatment. A second strategy involves tumor-specific targeting to enhance drug delivery specificity and drug internalization. In addition, we review the potential of combinations of the two in one targeted thermosensitive-triggered drug delivery system.
Heat-triggered drug delivery using thermosensitive liposomes as well as the use of tumor vasculature or tumor cell-targeted liposomes are both promising strategies to improve liposomal chemotherapy. Preclinical evidence has been encouraging and both strategies are currently undergoing clinical evaluation. A combination of both strategies rendering targeted thermosensitive liposomes (TTSL) may appear as a new and attractive approach promoting tumor drug delivery.
目前可用的化疗受到肿瘤特异性和由此产生的毒性缺乏的限制。小而长循环的脂质体可以在从肿瘤血管外渗后优先将化疗药物递送到肿瘤中。尽管临床使用的脂质体制剂显示出毒性显著降低,但治疗活性的增强并未完全达到预期。
脂质体制剂中的药物生物利用度低和肿瘤积累有限仍然是进一步提高脂质体化疗治疗活性的主要挑战。本文综述的目的是强调解决这些挑战的策略。第一种策略使用热疗和热敏脂质体来提高肿瘤积累并触发脂质体药物生物利用度。图像引导可以帮助在线监测热量和药物输送,并进一步实现治疗个体化。第二种策略涉及肿瘤特异性靶向,以增强药物传递的特异性和药物内化。此外,我们还综述了两种策略在一个靶向热敏触发药物传递系统中的联合应用潜力。
使用热敏脂质体的热触发药物输送以及使用肿瘤血管或肿瘤细胞靶向脂质体都是提高脂质体化疗的有前途的策略。临床前证据令人鼓舞,这两种策略都正在进行临床评估。使靶向热敏脂质体(TTSL)的两种策略相结合可能成为一种新的有吸引力的方法,促进肿瘤药物输送。