Multifunctional biocompatible Ni/Ni–P nanospheres for anti-tumor “neoadjuvant phototherapy” combining photothermal therapy and photodynamic therapy

Abstract

Gastric cancer, a gastrointestinal tumor with high morbidity and lethality, is often treated using strategies that are not as effective as they could be due to the locally advanced stage. Although pre-operative neoadjuvant chemotherapy can degrade the tumor stage to afford the possibility of surgery, it still possesses the problems of high systemic toxicity and low selectivity. In this work, we constructed an intelligent multi-functional nanoplatform (NNPIP NPs) with synergistic effects of photothermal therapy (PTT) and photodynamic therapy (PDT), which consisted of the nickel/nickel phosphide (Ni/Ni–P) nanosphere as the core, polyethyleneimine (PEI) as the shell, and the loaded indocyanine green (ICG). The mutual reinforcement of heat generated by the core and photosensitizer under 808 nm NIR laser irradiation is highly effective in the synergistic action of PTT. And co-delivery of ICG with nanoparticles into the cell enhances the PDT effect by reducing the consumption of singlet oxygen (¹O₂). Ultimately, this therapeutic strategy in vivo not only shrunk tumors but even eliminated tumors completely in a quarter of samples, which may be considered as a potential alternative to neoadjuvant chemotherapy and called “neoadjuvant phototherapy”. In addition, as a nanoplatform based on transition metal nickel, NNPIP NPs could also be considered as a potential contrast agent for T₁-weighted magnetic resonance imaging (MRI). Herein, we can diagnose and achieve pre-surgical downstaging of tumors and hope to improve R0 resection rates with lower toxicity and higher selectivity.