Pramanik Prithankar, Halder Debdatta, Jana Siddhartha Sankar, Ghosh Suhrit
Polymer Science Unit, Indian Association for the Cultivation of Science, Jadavpur, Kolkata, 700032, India.
Department of Biological Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata, 700032, India.
Macromol Rapid Commun. 2016 Sep;37(18):1499-506. doi: 10.1002/marc.201600260. Epub 2016 Jul 22.
The synthesis, micellar aggregation, and pH-triggered intracellular drug delivery ability of an amphiphilic statistical copolymer (P2) are studied. Two methacrylate derivatives, one containing a hydrophilic pendant and the other containing a hydrophobic pendant chain, are copolymerized to produce P2. The hydrophobic pendant chain is linked to the polymer backbone by a β-thiopropionate linkage, known to undergo slow hydrolysis at mild acidic pH. P2 forms a multimicellar cluster in water with a critical aggregation concentration of 0.02 mg mL(-1) and encapsulates a hydrophobic guest such as pyrene, Nile red, or the anti-cancer drug doxorubicin (Dox). Sustained release of the entrapped Dox (80% after 100 h) is noticed at pH 5.2, while release is significantly slower (35% after 100 h) at pH 7.4. Acidic hydrolysis of the β-thiopropionate linkage leading to the reduction of the hydrophobicity is established as the cause for micellar disassembly and triggered drug release. Cell-culture studies with the human breast cancer cell line, MCF-7, reveal biocompatibility of P2 (below 150 μg mL(-1) ). It is further tested for intracellular delivery of Dox. MCF-7 cells remain healthy at pH 7.4 but become unhealthy at pH 5.2 when treated with a Dox-loaded P2 micelles.
研究了一种两亲性无规共聚物（P2）的合成、胶束聚集以及pH触发的细胞内药物递送能力。将两种甲基丙烯酸酯衍生物进行共聚以制备P2，其中一种含有亲水性侧基，另一种含有疏水性侧链。疏水性侧链通过β-硫代丙酸酯键连接到聚合物主链上，已知该键在温和酸性pH下会缓慢水解。P2在水中形成多胶束聚集体，临界聚集浓度为0.02 mg mL⁻¹，并包封了诸如芘、尼罗红或抗癌药物阿霉素（Dox）等疏水性客体。在pH 5.2时，包封的Dox会持续释放（100小时后释放80%），而在pH 7.4时释放明显较慢（100小时后释放35%）。β-硫代丙酸酯键的酸性水解导致疏水性降低，这被确定为胶束解体和触发药物释放的原因。用人乳腺癌细胞系MCF-7进行的细胞培养研究表明P2具有生物相容性（低于150 μg mL⁻¹）。进一步测试了其对Dox的细胞内递送能力。在pH 7.4时，MCF-7细胞保持健康，但在用负载Dox的P2胶束处理时，在pH 5.2时会变得不健康。
