Development and characteristics of novel sonosensitive liposomes for vincristine bitartrate

The aim of drug delivery is to increase therapeutic efficacy. Externally triggered drug delivery systems enable site-specific and time-controlled drug release. To achieve this goal, our strategy was based on ultrasound-triggered release of an anticancer agent from sonosensitive liposomes (SL). To realize the ultrasound-triggered drug release, a lipophilic sonosensitizer, hematoporphyrin monomethyl ether (HMME) was incorporated into the lipid bilayer of liposomes. Once irradiated by the ultrasound in tumor tissues, the sonodynamic effect generated by HMME could lead to an efficient disruption of the lipid bilayer in the SL. After encapsulating vincristine bitartrate (VIN) as the model drug, the ultrasound-triggered lipid bilayer breakdown can trigger the instant release of VIN, enabling ultrasound-controlled chemotherapy with great specificity. In the <i>in vitro</i> and <i>in vivo</i> studies, by integrating tumor-specific targeting and stimuli-responsive controlled release into one system, VIN-loaded SL showed excellent antitumor efficacy. The SL could potentially produce viable clinical strategies for improved targeting efficiency of VIN for the treatment of related cancer. More importantly, this report provides an example of controlled release by means of a novel class of ultrasound triggering system.

药物递送的核心目标在于提升治疗疗效。外触发型药物递送系统可实现位点特异性与时间可控的药物释放。为达成该目标，本研究采用的策略基于超声触发声敏脂质体（sonosensitive liposomes，SL）释放抗癌剂。为实现超声触发的药物释放，我们将亲脂性声敏剂单甲基卟啉醚（hematoporphyrin monomethyl ether，HMME）嵌入脂质体的脂质双分子层中。当肿瘤组织内的声敏脂质体受到超声辐照时，HMME产生的声动力效应可高效破坏其脂质双分子层。以重酒石酸长春新碱（vincristine bitartrate，VIN）作为模型药物完成包载后，超声触发的脂质双分子层破裂可引发VIN的即时释放，从而实现特异性极强的超声调控化疗。在体外（in vitro）与体内（in vivo）实验中，将肿瘤靶向特异性与刺激响应型控释整合于单一系统的载VIN声敏脂质体展现出优异的抗肿瘤疗效。该声敏脂质体有望为提升VIN的靶向递送效率以治疗相关癌症提供可行的临床策略。更为重要的是，本研究为利用新型超声触发系统实现药物控释提供了范例。