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

Abstract

Background: 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. Methods: 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 in vivo and in vitro studies. Results: 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. Conclusions: 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.

Nanoformulations in Pharmaceutical and Biomedical Applications: Green Perspectives

“…Vegetable oils, including soybean oil and palm oil, together with fatty acids and medium-chain triglycerides, are optimal selections for the oily core of nanocapsules due to their capacity to break down lipophilic medications and the safety they offer to the oil phase. The oil serves as a medicine solvent and provides therapeutic advantages, making it a good option for the core of nanocapsules [ 211 , 212 ].…”

“…Gemcitabine hydrochloride and doxorubicin, hydrophilic anti-cancer drugs, have been efficiently encapsulated in polymeric nanocapsules containing an aqueous core. Nanocapsules containing drugs showed better effectiveness in fighting cancer than the medicine alone [ 212 ]. Polymeric nanocapsules containing an aqueous core can efficiently enclose and safeguard hydrophilic bioactive compounds.…”