Background: Platinum(IV) complexes with inflammation inhibitory properties are much favored in improving antitumor activities. Nanodrug-delivery system as a preferable measure for antitumor therapy are widely explored in platinum(IV) drug delivery.
Purpose: The aim for this study was to develop novel bovine serum albumin (BSA) nanoparticles (NPs) based on naproxen platinum(IV) complexes to display a synergistic antitumor mechanism targeting cyclooxygenase-2 (COX-2), metalloproteinase-9 (MMP-9) and inducible nitric oxide synthase (iNOS).
Methods: Herein, we reported the preparation of two BSA NPs of naproxen platinum(IV) complexes, and their antitumor activities were investigated in vitro and in vivo.
Results: Both NPs possessed relatively uniform size and good stability for 30 days in aqueous solution. They exhibited prominent antitumor activities in vitro, and showed great potential in reversing drug resistance. Furthermore, these two NPs played superior tumor growth suppression in vivo in contrast to the free compounds, which were comparable to that of cisplatin and oxaliplatin, but induced lower toxic influences than platinum(II) drugs especially to spleen and liver. Moreover, the naproxen platinum(IV) NPs could decrease tumor inflammation targeting COX-2, MMP-9 and iNOs, and decreasing NO production, which would be in favor of enhancing the antitumor competence, and reducing toxicity.
Conclusion: Taken together, BSA NPs of naproxen platinum(IV) complexes demonstrated a powerful antitumor efficacy in vitro and in vivo. The platinum(IV) NPs with inflammation inhibitory competence targeting multiple enzymes reported in this work afford a new strategy for the development of antitumor therapy to overcome drawbacks of clinical platinum(II) drugs.



中文翻译：

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具有炎症抑制能力的白蛋白封装的奈普生铂 (IV) 复合物纳米颗粒在体外和体内表现出有效的抗肿瘤活性


背景：具有炎症抑制特性的铂（IV）络合物在提高抗肿瘤活性方面备受青睐。纳米药物输送系统作为抗肿瘤治疗的优选措施在铂（IV）药物输送中得到了广泛的探索。

目的：本研究的目的是开发基于萘普生铂（IV）复合物的新型牛血清白蛋白（BSA）纳米颗粒（NP），以展示针对环加氧酶-2（COX-2）、金属蛋白酶-9（MMP）的协同抗肿瘤机制-9) 和诱导型一氧化氮合酶 (iNOS)。

方法：本文报道了两种萘普生铂(IV)配合物BSA NPs的制备，并研究了它们的体外和体内抗肿瘤活性。

结果：两种纳米粒子均具有相对均匀的尺寸和在水溶液中30天的良好稳定性。它们在体外表现出显着的抗肿瘤活性，并在逆转耐药性方面显示出巨大的潜力。此外，与游离化合物相比，这两种纳米粒子在体内发挥了更优异的肿瘤生长抑制作用，与​​顺铂和奥沙利铂相当，但比铂(II)药物引起的毒性影响更低，尤其是对脾和肝的毒性影响。此外，萘普生铂(IV)纳米粒可以减轻针对COX-2、MMP-9和iNOs的肿瘤炎症，减少NO的产生，有利于增强抗肿瘤能力，降低毒性。

结论：综上所述，萘普生铂（IV）配合物的BSA NPs在体外和体内表现出强大的抗肿瘤功效。本研究报道的具有针对多种酶的炎症抑制能力的铂（IV）纳米颗粒为抗肿瘤治疗的发展提供了新的策略，以克服临床铂（II）药物的缺点。