用于肿瘤的光声成像和光热治疗的诊疗酞菁和萘菁纳米粒子。

Theranostic Phthalocyanine and Naphthalocyanine Nanoparticles for Photoacoustic Imaging and Photothermal Therapy of Tumors.

机构信息

Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA.

Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.

出版信息

Nanotheranostics. 2024 Jan 1;8(1):100-111. doi: 10.7150/ntno.88892. eCollection 2024.

Abstract

Phthalocyanine (PC) and naphthalocyanine (NC) dyes have long garnered interest as theranostic agents for optical imaging and phototherapy due to their near-infrared absorbance, photostability, imaging contrast, and proven safety in clinical trials. Yet, only a small fraction of these dyes has been evaluated as photothermal therapy (PTT) agents for cancer treatment. Nearly 40 distinct NC and PC dyes were encapsulated within polymeric PEG-PCL micelles via oil-in-water emulsions. The optimal NC/PC-loaded micelle formulations for PTT and photoacoustic (PA) imaging were identified through and studies. The most promising candidate, CuNC(Octa)-loaded micelles, demonstrated a strong PA signal with a peak absorbance at ~870 nm, high photothermal efficiency, and photostability. The CuNC(Octa)-loaded micelles exhibited heat generation as good or better than gold nanorods/nanoshells and >10-fold higher photoacoustic signals. Micelle preparation was reproducible/scalable, and the CuNC(Octa)-loaded micelles are highly stable under physiological conditions. The CuNC(Octa)-loaded micelles localize within tumors via enhanced permeability and retention and are readily detectable by PA imaging. In a syngeneic murine tumor model of triple-negative breast cancer, CuNC(Octa)-loaded micelles demonstrate efficient heat generation with PTT, leading to the complete eradication of tumors. CuNC(Octa)-loaded micelles represent a promising theranostic agent for PA imaging and PTT. The ability to utilize conventional ultrasound in combination with PA imaging enables the simultaneous acquisition of information about tumor morphology and micelle accumulation. PTT with CuNC(Octa)-loaded micelles can lead to the complete eradication of highly invasive tumors.

摘要

酞菁(PC)和萘菁(NC)染料由于其近红外吸收、光稳定性、成像对比度以及在临床试验中的安全性已被长期研究作为光学成像和光疗的治疗试剂。然而,只有一小部分这些染料被评估为用于癌症治疗的光热疗法(PTT)试剂。将近 40 种不同的 NC 和 PC 染料通过油包水乳液被包裹在聚合物 PEG-PCL 胶束内。通过和研究,确定了用于 PTT 和光声(PA)成像的最佳 NC/PC 负载胶束制剂。最有前途的候选物是负载 CuNC(Octa)的胶束,其具有约 870nm 处的强 PA 信号、高光热效率和光稳定性。负载 CuNC(Octa)的胶束表现出与金纳米棒/纳米壳相当或更好的发热性能,并且光声信号高 10 倍以上。胶束制备具有重现性/可扩展性,并且负载 CuNC(Octa)的胶束在生理条件下高度稳定。负载 CuNC(Octa)的胶束通过增强的渗透性和保留作用在肿瘤内定位,并可通过 PA 成像轻易检测到。在三阴性乳腺癌的同种异体小鼠肿瘤模型中,负载 CuNC(Octa)的胶束通过 PTT 实现高效发热,导致肿瘤完全消除。负载 CuNC(Octa)的胶束是一种很有前途的用于 PA 成像和 PTT 的治疗试剂。能够结合传统超声和 PA 成像的能力使得能够同时获取关于肿瘤形态和胶束积累的信息。负载 CuNC(Octa)的胶束的 PTT 可以导致高度侵袭性肿瘤的完全消除。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d16f/10750118/4b4fa09c6bae/ntnov08p0100g001.jpg

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