Smart Human Serum Albumin-Indocyanine Green Nanoparticles Generated by Programmed Assembly for Dual-Modal Imaging-Guided Cancer Synergistic Phototherapy

TLDR

Phototherapy, including photodynamic and photothermal approaches, is a light‑activated local treatment modality currently under intensive preclinical and clinical investigation for cancer. The study aims to improve phototherapy efficacy and reduce light‑associated side effects by enhancing drug accumulation and enabling precision‑guided conversion of absorbed light into reactive oxygen species and hyperthermia. A programmed assembly strategy was employed to fabricate human serum albumin–indocyanine green nanoparticles through intermolecular disulfide conjugation. These nanoparticles accumulated highly in tumors (T/N ratio 36.12±5.12 at 24 h) and persisted for over seven days, allowing clear dual‑modal NIR fluorescence and photoacoustic imaging, while simultaneously generating ROS and hyperthermia under a single NIR laser to achieve complete tumor ablation without recurrence or toxicity, highlighting their potential as imaging‑guided synergistic PDT/PTT theranostics.

Abstract

Phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), is a light-activated local treatment modality that is under intensive preclinical and clinical investigations for cancer. To enhance the treatment efficiency of phototherapy and reduce the light-associated side effects, it is highly desirable to improve drug accumulation and precision guided phototherapy for efficient conversion of the absorbed light energy to reactive oxygen species (ROS) and local hyperthermia. In the present study, a programmed assembly strategy was developed for the preparation of human serum albumin (HSA)-indocyanine green (ICG) nanoparticles (HSA-ICG NPs) by intermolecular disulfide conjugations. This study indicated that HSA-ICG NPs had a high accumulation with tumor-to-normal tissue ratio of 36.12±5.12 at 24 h and a long-term retention with more than 7 days in 4T1 tumor-bearing mice, where the tumor and its margin, normal tissue were clearly identified via ICG-based in vivo near-infrared (NIR) fluorescence and photoacoustic dual-modal imaging and spectrum-resolved technology. Meanwhile, HSA-ICG NPs efficiently induced ROS and local hyperthermia simultaneously for synergetic PDT/PTT treatments under a single NIR laser irradiation. After an intravenous injection of HSA-ICG NPs followed by imaging-guided precision phototherapy (808 nm, 0.8 W/cm2 for 5 min), the tumor was completely suppressed, no tumor recurrence and treatments-induced toxicity were observed. The results suggest that HSA-ICG NPs generated by programmed assembly as smart theranostic nanoplatforms are highly potential for imaging-guided cancer phototherapy with PDT/PTT synergistic effects.