脂质体递药系统的靶向修饰

Targeting Modification of Liposome Drug Delivery System

作为药物递送载体,脂质体(LPs)由于免疫原性低、稳定性好、毒性低和成本低而被认为是有前途的纳米药物递送系统。然而,LPs的靶向递送效果并不理想,往往会对正常的机体细胞造成伤害,因此,如何优化LPs药物,使其具有靶向性仍然是当前研究的重点。本文结合近年来国内外相关研究进展,重点介绍了多肽、抗体、糖类、配体,以及核酸适配体等靶向修饰物对LPs功能的影响,并归纳总结了各种靶向修饰目前存在的优势与挑战,以期对LPs给药系统的进一步研究提供科学参考及新药研发提供理论依据。

Liposomes are hollow spheres composed of lipids bilayer membranes,which can encapsulate and deliver hydrophilic and hydrophobic substances.Liposomes are promising nano-drug delivery systems due to low immunogenicity,good stability,low toxicity and cost.Currently,a variety of liposome drugs for tumor treatment have been listed.Liposomes can accumulate in tumor tissues via enhanced permeability and retention effect(EPR)and are internalized into tumor cells by endocytosis or pinocytosis.Subsequently,liposomes are intracellularly cleaved to release drugs,thereby killing tumor cells.Liposomes that rely on the EPR effect are called passive targeting liposomes,which lack the ability to specifically recognize target tissues.However,active targeting liposomes can achieve targeting delivery via the specific binding between the targeting modifiers on the surface of liposomes and receptors on the surface of tumor cells.These receptors such as peptides,carbohydrates,ligands,antibodies and nucleic acid aptamers on the surface of tumor cells overexpress due to rapid growth of tumor cells and needs of nutrients and related growth factors.Thus,liposomes can be reasonably designed according to these specific receptors.Recent years,some studies have reported biomimetic liposomes by coating the cell membrane on the surface of liposomes,however,the research on biomimetic liposomes is still in its infancy,and there are still many problems to be solved.Additionally,since the length is limited,biomimetic liposomes are not reviewed in this paper.Taken together,liposomes as potential drug carriers,not only protect drugs,but also reduce side effects,importantly,they can precisely target tumor tissues through introducing targeting modifiers.In this work,we review the improvement of targeting function of liposome by five targeting modifiers including peptides,carbohydrates,ligands,antibodies and nucleic acid aptamers,and summarize the existing advantages and challenges of various targeted modifications.Finally,this review is expected to provide scientific reference for the LPs drug delivery system study and theoretical basis for the drug development.