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目的:制备2种正电化修饰的N-(2-羟丙基)甲基丙烯酰胺(HPMA)聚合物-阿霉素接合物并表征,分别考察2种接合物的正电基团含量对肿瘤细胞摄取的影响。方法:制备侧链带伯胺基的HPMA聚合物-阿霉素接合物(pHPMA-DOX-APMA)和侧链带胍基的HPMA聚合物-阿霉素接合物(pHPMA-DOX-GPMA),对其药剂学性质如正电基团含量,载药量,Zeta电位和分子量进行表征,进一步考察不同正电基团含量的接合物对MCF-7细胞摄取和毒性的影响。结果:通过自由基聚合反应,2种接合物成功合成。其中pHPMA-DOX-APMA伯胺基含量为0.44~1.57 mmol·g-1,载药量为7.15%~9.25%;pHPMA-DOX-GPMA胍基含量为0.11~0.54 mmol·g-1,载药量为7.55%~9.07%;相对分子质量分别为33~38 kDa和32~37kDa。通过BCA法和MTT法研究分别发现在pHPMA-DOX-APMA中的伯胺基团含量为1.570 mmol·g-1及pHPMA-DOXGPMA中的胍基含量为0.260 mmol·g-1时,肿瘤细胞对阿霉素的摄取量显著增加,二者的IC50与pHPMA-DOX相比显著降低(P<0.05)。结论:成功制备了2种正电化修饰的HPMA聚合物-阿霉素接合物;适当的正电化修饰对阿霉素的肿瘤细胞摄取有促进作用。
OBJECTIVE: To prepare and characterize two kinds of electrochemically modified N- (2-hydroxypropyl) methacrylamide (HPMA) polymer doxorubicin conjugates and investigate the effect of the positive group content of the two conjugates on tumor Effects of cellular uptake. Methods: HPMA polymer-doxorubicin conjugate (pHPMA-DOX-GPMA) with side-chain primary amino groups and doxorubicin conjugate (pHPMA-DOX-GPMA) The pharmacological properties such as the positive group content, drug loading, Zeta potential and molecular weight were characterized. Further investigation was made on the influence of the conjugates with different positive groups on the uptake and toxicity of MCF-7 cells. Results: Two kinds of conjugates were successfully synthesized by free radical polymerization. The content of primary amino group of pHPMA-DOX-APMA was 0.44-1.57 mmol · g-1, and the drug loading was 7.15% -9.25%. The content of guanidine in pHPMA-DOX-GPMA was 0.11-0.54 mmol · g-1, The amount of 7.55% ~ 9.07%; relative molecular mass of 33 ~ 38 kDa and 32 ~ 37kDa. The results of BCA assay and MTT assay showed that when the content of primary amine group in pHPMA-DOX-APMA was 1.570 mmol · g-1 and the content of guanidine in pHPMA-DOXGPMA was 0.260 mmol · g-1, The uptake of doxorubicin increased significantly, and the IC50 of both groups was significantly lower than that of pHPMA-DOX (P <0.05). CONCLUSION: Two positively charged modified HPMA polymers, doxorubicin conjugates, were successfully prepared. Appropriate electroporation could promote the uptake of doxorubicin into tumor cells.