A Laser-Activated Biocompatible Theranostic Nanoagent for Targeted Multimodal Imaging and Photothermal Therapy

Abstract

Multifunctional nanoparticles have been reported for cancer detection and treatment currently. However, the accurate diagnosis and efficient treatment for tumors are still not satisfied. Here we report on the development of targeted phase change multimodal polymeric nanoparticles for the imaging and treatment of HER2-positive breast cancer.Methods: We evaluated the multimodal imaging capabilities of the prepared nanoparticles in vitro using agar-based phantoms. The targeting performance and cytotoxicity of the nanoparticles were examined in cell culture using SKBR3 (over-expressing HER2) and MDA-MB-231 (HER2 negative) cells. We then tested the magnetic resonance (MR)/ photoacoustic (PA)/ ultrasound (US)/ near-infrared fluorescence (NIRF) multimodal imaging properties and photothermal effect of the nanoparticles in vivo using a SKBR3 breast xenograft model in nude mice. Tissue histopathology and immunofluorescence were also conducted.Results: Both in vitro and in vivo systematical studies validated that the hybrid nanoparticles can be used as a superb MR/US/PA/NIRF contrast agent to simultaneously diagnose and guide tumor photothermal therapy (PTT). When irradiated by a near infrared laser, the liquid PFP vaporizes to a gas, rapidly expelling the contents and damaging surrounding tissues. The resulting micro-sized bubbles provide treatment validation through ultrasound imaging. Localization of DIR and SPIO in the tumor region facilitate photothermal therapy for targeted tumor destruction. The mice treated with HER2 targeted nanoparticles had a nearly complete response to treatment, while the controls showed continued tumor growth.Conclusion: This novel theranostic agent may provide better diagnostic imaging and therapeutic potential than current methods for treating HER2-positive breast cancer.

Photothermal therapy and photoacoustic imaging via nanotheranostics in fighting cancer

“…Other imaging techniques, such as OCT, ultrasound imaging or CT, have also been used to guide the PTT. 27,99,218,219,[243][244][245] Each imaging technique has its own pros and cons. For example, MRI is mainly used for soft tissues, but its resolution is lower than CT.…”

GSH-sensitive Pt(IV) prodrug-loaded phase-transitional nanoparticles with a hybrid lipid-polymer shell for precise theranostics against ovarian cancer

“…Alternatively, nanosized UCAs containing drugs or genes have been steadily developed as a new generation of UCAs to overcome these limitations and to treat tumors, because of the phase-transition behavior of the nanosized UCAs 21-24. Nanosized UCAs typically consist of a perfluorocarbon core in the form of a liquid and a shell made from materials such as proteins 25, lipids 26-28, polymers 29, 30, and silica 31, 32. However, there are still some challenges in the development of UCAs.…”

Dual-mode imaging and therapeutic effects of drug-loaded phase-transition nanoparticles combined with near-infrared laser and low-intensity ultrasound on ovarian cancer

“…Various photosensitizer nano-composites have been used for PA imaging (Cho et al., 2010 ; Liu et al., 2016b ; Zhang et al., 2016 ; Lemaster & Jokerst, 2017 ). Among them, ICG-based nanoparticles can be used as PA contrast agents due to their intense and stable signal (Chen et al., 2016 ; Gao et al., 2016 ; Deng et al., 2017 ). After being vaporized via optical irradiation and acoustic pressure, PFC can change its phase and subsequently generate gas (Krafft, 2001 ).…”