A novel treatment for metastatic lymph nodes using lymphatic delivery and photothermal therapy

Adewale O Oladipo,Oluwatobi S Oluwafemi,Ariunbuyan Sukhbaatar,Atsuki Komiya,Junnosuke Okajima,Tetsuya Kodama,Shigenao Maruyama,Shiro Mori,Sandile P Songca

doi:10.1038/srep45459

Abstract

Systemic delivery of an anti-cancer agent often leads to only a small fraction of the administered dose accumulating in target sites. Delivering anti-cancer agents through the lymphatic network can achieve more efficient drug delivery for the treatment of lymph node metastasis. We show for the first time that polymeric gold nanorods (PAuNRs) can be delivered efficiently from an accessory axillary lymph node to a tumor-containing proper axillary lymph node, enabling effective treatment of lymph node metastasis. In a mouse model of metastasis, lymphatic spread of tumor was inhibited by lymphatic-delivered PAuNRs and near-infrared laser irradiation, with the skin temperature controlled by cooling. Unlike intravenous injection, lymphatic injection delivered PAuNRs at a high concentration within a short period. The results show that lymphatic administration has the potential to deliver anti-cancer agents to metastatic lymph nodes for inhibition of tumor growth and could be developed into a new therapeutic method.

Highlights

Near-infrared (NIR) laser radiation to nanoparticles causes strong light absorption and subsequent rapid and efficient conversion of photon energy into heat, leading to irreversible thermal damage to proteins and DNA13–16
In our model of lymph nodes (LNs) metastasis, tumor cells were inoculated into the SiLN to induce metastasis in the PALN via lymphatic vessels, and PAuNRs were injected into the AALN to deliver them to the PALN
The mechanism underlying metastasis in this model differs from that underlying metastasis from a solid tumor in a physiological system, the reproducibility of the model allowed us to focus on the main aim of our study, namely to investigate the therapeutic effects of combining PAuNRs delivered by a lymphatic drug delivery system with NIR laser light irradiation

Summary

Introduction

Near-infrared (NIR) laser radiation to nanoparticles causes strong light absorption and subsequent rapid and efficient conversion of photon energy into heat, leading to irreversible thermal damage to proteins and DNA13–16. We use an in vivo mouse model of LN metastasis to demonstrate the lymphatic delivery of polyethylene glycol (PEG)-modified gold nanorods (PAuNRs) and investigate the effects of NIR laser irradiation on tumor growth in the PALN (Fig. 1A). To treat deeply embedded tumor cells and prevent skin burns, the laser intensity needed for hyperthermia was adjusted to heat the PALN to 45 °C while the surface temperature of the overlying skin was cooled with water (Fig. 1B). This procedure differs from established local/systemic delivery methods as it can deliver a high concentration of gold nanorods (AuNRs) to metastatic LNs within a short time

Methods

Results

Conclusion