Boron-containing folate receptor-targeted liposomes as potential delivery agents for neutron capture therapy
Boron-containing folate receptor-targeted liposomes as potential delivery agents for neutron capture therapy
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DOI：
10.1021/bc015557y
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发表时间：
2002-05-01
影响因子：
4.7
通讯作者：
Lee, RJ
中科院分区：
文献类型：
--
作者：
Pan, XQ;Wang, HQ;Lee, RJ
硼中子俘获疗法（BNCT）依赖于选择性地向肿瘤细胞递送足够数量的B-10原子，以维持致命的B-10(n, α)Li-7反应。FR在人类肿瘤中的表达频繁扩增。本研究的目的是研究叶酸受体（FR）靶向脂质体作为一系列含硼剂的潜在载体。将Na-2[B12H11SH]和Na-3 （B20H17NH3）两种高离子化硼化合物通过被动负载的方式掺入脂质体，包封率分别为6%和15%。此外，还研究了5种弱碱性硼化多胺。其中两种是亚精胺衍生物：N-5-（4-碳硼基丁基）亚精胺- 3hcl （SPD-5）、N-5-[4-（2-氨基乙基-o-碳硼基）丁基]亚精胺。4盐酸(ASPD-5)。三种是精胺衍生物：N-5-（4-碳硼基丁基）精胺。4HCl (SPM-5), N-5-[4-（2-氨基乙基-o-碳硼基）丁基]精胺。（NN10）- n -5-双（4-碳硼基丁基）精胺盐酸(SPM-5, 10)。通过ph梯度驱动的远程加载方法将这些化合物加入脂质体中，其加载效率受特定捕获剂和硼化合物结构的影响。与柠檬酸钠相比，以硫酸铵为捕集剂的低分子量硼衍生物获得了更高的装载效率。用扩增FR表达的人KB鳞状上皮癌细胞研究了叶酸衍生的硼化脂质体的体外摄取。无论硼的化学形式和脂质体制备方法如何，fr靶向脂质体比非靶向对照脂质体（每10(9)个细胞高达1584马克）观察到更高的细胞硼摄取（每10(9)个细胞高达154马克）。fr靶向脂质体的KB细胞结合是饱和的，可被1mm游离叶酸阻断。我们的研究结果表明，有必要进一步评估fr靶向脂质体作为中子捕获治疗硼载体的潜力。
Boron neutron capture therapy (BNCT) depends on the selective delivery of a sufficient number of B-10 atoms to tumor cells to sustain a lethal B-10(n,alpha)Li-7 reaction. Expression of FR frequently is amplified among human tumors. The goal of the present study was to investigate folate receptor (FR)-targeted liposomes as potential carriers for a series of boron-containing agents. Two highly ionized boron compounds, Na-2[B12H11SH] and Na-3 (B20H17NH3), were incorporated into liposomes by passive loading with encapsulation efficiencies of 6% and 15%, respectively. In addition, five weakly basic boronated polyamines were investigated. Two were the spermidine derivatives: N-5-(4-carboranylbutyl)spermidine-3HCl (SPD-5), N-5-[4-(2-aminoethyl-o-carboranyl)butyl]spermidine.4HCl (ASPD-5). Three were the spermine derivatives: N-5-(4-carboranylbutyl)spermine.4HCl (SPM-5), N-5-[4-(2-aminoethyl-o-carboranyl)butyl]spermine.5HCl (ASPM-5), and (NN10)-N-5-bis(4-carboranylbutyl)spermine.4 HCl (SPM-5,10). These were incorporated into liposomes by a pH-gradient-driven remote-loading method with varying loading efficiencies, which were influenced by the specific trapping agent and the structure of the boron compound. Greater loading efficiencies were obtained with lower molecular weight boron derivatives, using ammonium sulfate as the trapping agent, compared to those obtained with sodium citrate. The in vitro uptake of folate-derivatized, boronated liposomes was investigated using human KB squamous epithelial cancer cells, which have amplified FR expression. Higher cellular boron uptake (up to 1584 mug per 10(9) cells) was observed with FR-targeted liposomes than with nontargeted control liposomes (up to 154 mug per 10(9) cells), irrespective of the chemical form of the boron and the method used for liposomal preparation. KB cell binding of the FR-targeted liposomes was saturable and could be blocked by 1 mM free folic acid. Our findings suggest that further evaluation of FR-targeted liposomes is warranted to assess their potential as boron carriers for neutron capture therapy.