Poly-amino acids coated gold nanorod and doxorubicin for synergistic photodynamic therapy and chemotherapy in ovarian cancer cells.

Jinying Liu,Wei Kou,Wei Ma,Rui Huang,Jin Zhao,Lina Shang

doi:10.1042/bsr20192521

Abstract

In this work, we have successfully designed and formulated a doxorubicin-loaded polypeptide-based multilayer assembled gold nanorod (DH-GNR). We have hypothesized that near-infrared (NIR) laser irradiation of DH-GNR will combine the benefits of chemotherapy and photothermal therapy. The GNR was surface functionalized with poly-glutamic acid (PGA) and poly-l-Lysine (PLL) with a final layer of hyaluronic acid (HA) that could also serve as a targeting ligand toward the overexpressed CD44 receptors in ovarian cancer cells. The zigzag ζ potential of nanoparticle is a proof of successful assembly of alternative polymers on the GNR surface. NIR irradiation exhibited a burst release of drug in pH 7.4 and pH 5.0 buffer conditions. The combination of doxorubicin (DOX)-based chemotherapy and GNR-based photothermal therapy exhibited a synergistic effect in killing the SKOV3 cancer cells. DH-GNR(+NIR) induced a 82.5% apoptosis (combined early and late apoptosis) compared with only 35.2 and 38.5% for DOX or DH-GNR(−NIR) treated cell group. Results clearly suggest that the excessive reactive oxygen species (ROS) generation in DH-GNR (+NIR) might be responsible for the cell apoptosis and cell death. The promising anticancer effect of DH-GNR will be of great potential in the treatment of ovarian cancers and worth further development for treating other malignant tumors.

Highlights

Ovarian cancer is a leading cause of gynecologic cancer-related deaths and second most cause of cancer-related deaths after breast cancer in women [1,2]
Third poly-glutamic acid (PGA) layer and fourth PLL layer was deposited and a characteristic zigzag ζ potential clearly reflect the alternative deposition of polymer materials on the gold nanorod (GNR) surface indicating the assembly of a definite polymer mass on the metallic nanoparticles
The results indicate that the high cytotoxicity induced by doxorubicin-loaded hyaluronic acid (HA)-coated gold nanorod (DH-GNR) might be strongly mediated by apoptosis induction

Summary

Introduction

Ovarian cancer is a leading cause of gynecologic cancer-related deaths and second most cause of cancer-related deaths after breast cancer in women [1,2]. Surgical resection is very effective, it is limited to the accessible tumors and complete removal is not possible in most of the cases [4,5]. The residual tumors pose a severe danger in the relapse of cancer. Systemic administration of chemotherapeutic drugs though effective in complete cancer cure after surgery, 90% of patients develop chemotherapy resistance and eventually fall for the cancer death [6]. Chemotherapeutic results in severe organ-related toxicity due to the non-specific distribution results in below-par therapeutic concentrations in the tumor tissues. Doxorubicin (DOX), an anthracycline moiety is one such drug indicated in the treatment of ovarian and many other cancers, DOX itself has toxicity concerns such as cardiotoxicity, nephrotoxicity, and myelosuppression [7,8]. It is important to design strategy to improve the anticancer effect of DOX and at the same time to decrease its side effects

Methods

Results

Conclusion