Abstract

Photodynamic therapy (PDT) is a promising treatment for malignancy. However, the low molecular solubility of photosensitizers (PSs) with a low accumulation at borderline malignant potential lesions results in the tardy and ineffective management of recurrent urothelial carcinoma. Herein, we used tannic acid (TNA), a green precursor, to reduce HAuCl4 in order to generate Au@TNA core-shell nanoparticles. The photosensitizer methylene blue (MB) was subsequently adsorbed onto the surface of the Au@TNA nanoparticles, leading to the incorporation of a PS within the organic shell of the Au nanoparticle nanosupport, denoted as Au@TNA@MB nanoparticles (NPs). By modifying the surface of the Au@TNA@MB NPs with the ligand folate acid (FA) using NH2-PEG-NH2 as a linker, we demonstrated that the targeted delivery strategy achieved a high accumulation of PSs in cancer cells. The cell viability of T24 cells decreased to 87.1%, 57.1%, and 26.6% upon treatment with 10 ppm[Au] Au@TNA/MB NPs after 45 min, 2 h, and 4 h of incubation, respectively. We also applied the same targeted PDT treatment to normal urothelial SV-HUC-1 cells and observed minor phototoxicity, indicating that this safe photomedicine shows promise for applications aiming to achieve the local depletion of cancer sites without side effects.

Highlights

  • Bladder cancer is the 10th most common cancer worldwide, with an estimated 549,000 new cases and 200,000 deaths each year [1]

  • Focal surgical intervention combined with minimally invasive therapeutic techniques for bladder cancer would alleviate the adverse effects and inconvenience caused by the long-term course of treatment [7]

  • The amount of methylene blue (MB) adsorbed onto the surface of Au@tannic acid (TNA) nanoparticles was calculated from the difference between the initial optical density of MB and each supernatant collected from centrifugation

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Summary

Introduction

Bladder cancer is the 10th most common cancer worldwide, with an estimated 549,000 new cases and 200,000 deaths each year [1]. 55% of NMIBC patients develop recurrence with limited treatment options, and 20% progress to muscle-invasive bladder cancer (MIBC) within 5 years [5]. Selectively targeting antibody-conjugated photosensitizers to tumors can protect normal urothelium cells and avert adverse events, the amount of drug delivered remains lower than those obtained using designed carriers based on polymerases, micelles, and high surface-to-volume ratio nanoparticles (NPs). Noncytotoxic materials such as gold, iron oxide, and silica NPs are becoming promising drug carrier platforms for biomedical applications [14,15]. Our approach used a targeted PS to deliver PDT and indicates that the promising next-generation development of selective PDT could be combined with photoimmunotherapy [10] for bladder tumor treatment

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