电荷翻转型药物载体用于肿瘤细胞核靶向药物输送的研究

Targeted Charge-Reversal Nanocarriers for Nuclear Drug Delivery

大多数的抗癌药物属于DNA毒化物,它们只有作用于细胞核中的DNA或与之相关的酶才能发挥药效。但是,癌细胞先天和后天获得的耐药机制能够有效地限制抗癌药物进入细胞核。目前研制的大多数药物载体只靶向细胞中的溶酶体、不能进入细胞核。最近,β-羧基酰胺化的阳离子聚合物如聚乙烯亚胺(PEI)和聚L-赖氨酸(PLL)被发展为从负电向正电翻转的新型细胞核靶向的药物载体,用于将药物直接输送到癌细胞的细胞核中,从而使药物避开肿瘤细胞膜及细胞浆中的多种耐药机制。在生理环境中,β-羧基酰胺化的阳离子聚合物带负电荷,抑制了阳离子聚合物与血液中蛋白质及细胞之间的非特异性相互作用。而当载体被癌细胞内吞并进入其酸性的溶酶体后,β-羧基酰胺键很快水解为胺基,载体又变为带正电荷,使载体能够逃离溶酶体并进入细胞核,将药物释放到细胞核中。实验结果表明,肿瘤靶向电荷翻转型药物载体能够有效地将药物输送到细胞核中,从而使药物避开癌细胞的耐药机制,提高药物疗效。本文就电荷翻转药物载体的进展做了简述。

Most anticancer drugs are DNA-toxins eliciting their pharmaceutical effects on nuclear DNA.However,the intrinsic and acquired drug resistance mechanisms of cancer cells efficiently limit their nuclear localization.Most current drug delivery systems target the cytoplasmic organelles,e.g.lysosomes,rather than nuclei.Recently,charge-reversal drug carriers based on β-carboxyl acid amidized cationic polymers,such as PEI and PLL,have been developed to deliver drugs into cancer cell nuclei.The β-carboxyl amidized ...