To enhance the therapeutic effects and reduce the damage to normal tissues in cancer chemotherapy, it is indispensable to develop drug delivery carriers with controllable release and good biocompatibility. In this work, acid-responsive and degradable polyphosphazene (PPZ) nanoparticles were synthesized by the reaction of hexachlorotripolyphosphonitrile (HCCP) with 4-hydroxy-benzoic acid (4-hydroxy-benzylidene)-hydrazide (HBHBH) and anticancer drug doxorubicin (DOX). The controlled release of DOX could be realized based on the acid responsiveness of acylhydrazone in HBHBH. Experimental results showed that polyphosphazene nanoparticles remained stable in the body’s normal fluids (pH ∼ 7.4), while they were degraded and controllable release of DOX in an acidic environment such as tumors (pH ∼ 6.8) and lysosome and endosome (∼5.0) in cancer cells In particular, the doxorubicin (DOX)-loading ratio was fair high and could be tuned from 10.6 to 52.6% by changing the dosing ratio of DOX to HBHBH. Meanwhile, the polyphosphazene nanodrugs showed excellent toxicity to tumor cells and reduced the side effect to normal cells both in vitro and in vivo due to their enhanced permeability and retention (EPR) effect and pH-sensitive degradation properties. Therefore, the constructed pH-sensitive drug delivery system has great potential for cancer chemotherapy.

中文翻译：

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酸响应性和可生物降解的聚磷腈纳米药物，可有效递送药物。

为了增强癌症化疗中的治疗效果并减少对正常组织的损害，开发具有可控释放和良好生物相容性的药物递送载体是必不可少的。在这项工作中，通过六氯三聚磷腈（HCCP）与4-羟基苯甲酸（4-羟基亚苄基）-酰肼（HBHBH）和抗癌药阿霉素（DOX）的反应合成了酸响应性和可降解的聚磷腈（PPZ）纳米颗粒。 。根据乙hydr对乙肝HBH的酸反应性，可以实现DOX的控释。实验结果表明，聚磷腈纳米颗粒在人体的正常体液（pH约为7.4）中保持稳定，而在酸性环境（例如肿瘤（pH约为6.8），溶酶体和内体（约5））中降解并可以受控地释放DOX。0）在癌细胞中，尤其是阿霉素（DOX）的负载率相当高，可以通过更改DOX与HBHBH的剂量比例从10.6调整到52.6％。同时，由于聚磷腈纳米药物具有增强的渗透性和保留（EPR）效果以及对pH敏感的降解特性，因此在体外和体内对肿瘤细胞均显示出优异的毒性，并减少了对正常细胞的副作用。因此，构建的pH敏感药物递送系统具有用于癌症化学疗法的巨大潜力。由于聚磷腈纳米药物具有增强的渗透性和保留（EPR）效果以及对pH敏感的降解特性，因此在体外和体内对肿瘤细胞均显示出优异的毒性，并减少了对正常细胞的副作用。因此，构建的pH敏感药物递送系统具有用于癌症化学疗法的巨大潜力。由于聚磷腈纳米药物具有增强的渗透性和保留（EPR）效果以及对pH敏感的降解特性，因此在体外和体内对肿瘤细胞均显示出优异的毒性，并减少了对正常细胞的副作用。因此，构建的pH敏感药物递送系统具有用于癌症化学疗法的巨大潜力。