Albumin-encapsulated Nanoparticles of Naproxen Platinum(IV) Complexes with Inflammation Inhibitory Competence Displaying Effective Antitumor Activities in vitro and in vivo

Abstract

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.

The potential of naproxen and its derivatives in inhibiting the processes of initiation, promotion and progression of cancerogenesis

“…Spadek aktywności PGE2w badaniu nad wysoce inwazyjnymi komórkami raka piersi MDA-MB-231, spowodowany inkubacją tych komórek in vitro z pochodną '4' nowo zsyntetyzowanych pochodnych naproksenu, skutkował opóźnieniem całkowitego tempa migracji komórek MDA-MB-231 [9]. Podobne właściwości antymigracyjne zaobserwowano w badaniach z udziałem nanocząsteczki platyny (IV) naproksenu in vitro oraz in vivo przeprowadzonych na czterech nowotworowych liniach komórkowych, w tym ludzkiego raka płuc (A549), ludzkiego raka jajnika (SKOV-3), mysiego raka okrężnicy (CT-26) i oporną na cisplatynę linię komórkową A549R raka wątroby [10].…”

“…Co więcej, MMP pełnią funkcję synergiczną z COX w promowaniu stanu zapalnego. MMP zostały uznane za potencjalne biomarkery diagnostyczne i prognostyczne w wielu typach i stadiach nowotworów [14,10].…”

“…Podobną zależność zaobserwowano w badaniu nad enkapsulowanymi w albuminie nanocząsteczkami kompleksów naproksenu platyny (IV) i ich aktywnością względem nowotworowych linii komórkowych in vitro i in vivo. Wykazano, że wspomniana pochodna naproksenu zmniejszała migrację komórek guza przez hamowanie aktywności MMP-9 [10].…”

Development of a series of flurbiprofen and zaltoprofen platinum(iv) complexes with anti-metastasis competence targeting COX-2, PD-L1 and DNA

“…1) and have displayed effective antitumor activities by arousing significant inhibition of cycloxygenases (COXs) to control the inflammatory response in tumor tissues besides causing serious DNA damage. 19–25…”

Hepatoprotective Effects of Albumin-Encapsulated Nanoparticles of a Curcumin Derivative COP-22 against Lipopolysaccharide/D-Galactosamine-Induced Acute Liver Injury in Mice

“…This can increase the targeted accumulation of drugs in the liver, and improve the bioavailability of free drugs, so as to significantly improve the therapeutic effect of ALI. Serum albumin nanocarriers have become one of the most promising carriers, because of their good biocompatibility, low immunogenicity, biodegradability, and good toxicological profiles [26][27][28][29]. Bovine serum albumin (BSA) has been widely studied, because of its high sequence homology (76.52%) with human serum albumin (HSA), wide sources, and low cost [30][31][32][33].…”