Abstract
Novel tumor-targeting titanium dioxide (TiO2) nanoparticles modified with hyaluronic acid (HA) were developed to explore the feasibility of exploiting the pH-responsive drug release property ofTiO2and the tumor-targeting ability of HA to construct a tumor-targeting cisplatin (CDDP) delivery system (HA-TiO2) for potential neoadjuvant chemotherapy of ovarian cancer. The experimental results indicated that CDDP release from the HA-TiO2nanoparticles was significantly accelerated by decreasing pH from 7.4 to 5.0, which is of particular benefit to cancer therapy. CDDP-loaded HA-TiO2nanoparticles increased the accumulation of CDDP in A2780 ovarian cancer cells via HA-mediated endocytosis and exhibited superior anticancer activityin vitro.In vivoreal-time imaging assay revealed that HA-TiO2nanoparticles possessed preferable tumor-targeting ability which might potentially minimize the toxic side effects of CDDP in clinical application.
Highlights
Ovarian cancer is a commonly fatal disease which is responsible for 4% of deaths from cancer in women
Our results indicated that the Hyaluronic acid (HA)-TiO2 nanoparticles had dimensions suitable for escaping rapid renal excretion, as well as avoiding components of the reticular endothelial system
TiO2 group remained almost the same level. These results clearly suggest that C6-loaded HA-TiO2 nanoparticles were internalized into cells via HA-mediated endocytosis
Summary
Ovarian cancer is a commonly fatal disease which is responsible for 4% of deaths from cancer in women. Conventional chemotherapeutic agents were distributed nonspecifically in the body when given intravenously They affect both cancerous and normal cells, thereby limiting the dose achievable within the tumor and resulting in suboptimal treatment due to excess toxicity [2]. Among various clinical applied chemotherapy drugs, cisplatin (cis-diamminedichloroplatinum (II), CDDP) has been demonstrated to be a promising one which shows preferable anticancer effect on ovarian cancer and has already been adopted in neoadjuvant chemotherapy of ovarian cancer for many years [18, 19]. With the aim of effectively delivering CDDP to the ovarian cancer site, we employed TiO2 NPs as a solid nano-sized vector. The HA-TiO2 nanoparticles were loaded with CDDP to construct a tumor-targeted delivery system with the hope to achieve preferable neoadjuvant chemotherapy of ovarian cancer
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