Harnessing light and ultrasonic vibration: efficient amphiphilic phthalocyanine-based sensitizers for combined sono-photodynamic therapy of breast cancer.

Authors

Hilal Çakmak, Aysegul Turkkol, Göknur Yaşa Atmaca, Umut Kerem Kolac, Fernando Aguilar-Galindo, Lukasz Sobotta, Mehmet Dincer Bilgin, Ali Erdoğmuş, Emre Güzel

Published in

Journal of materials chemistry. B. Aug 21, 2026. Epub Aug 21, 2026.

Abstract

The heterogeneity and global burden of breast cancer necessitate novel therapeutic strategies to circumvent resistance and mitigate systemic toxicity. Amphiphilic phthalocyanines have emerged as highly effective photosensitizers in photodynamic therapy, uniquely balancing aqueous solubility with lipid membrane affinity to overcome traditional aggregation quenching. By integrating structural features that promote selective subcellular accumulation, these amphiphilic phthalocyanine-based sensitizers significantly amplify targeted oxidative stress when exposed to combined light and ultrasonic stimuli. In this study, amphiphilic zinc- and indium-based phthalocyanine sensitizers are prepared. Notably, comprehensive photochemical investigations revealed that all phthalocyanine derivatives exhibit a pronounced enhancement in singlet oxygen generation under SPDT conditions (Φ_Δ = 0.89-0.98) compared to PDT (Φ_Δ = 0.39-0.49), highlighting the superior performance of InPc-based systems as highly efficient photosensitizers. The remarkable enhancement in Φ_Δ values under SPDT conditions (reaching up to 0.98) can be attributed to the synergistic interplay between ultrasonic cavitation-induced monomerization, which prevents self-aggregation of the amphiphilic macrocycles, and the sonoluminescence-triggered re-excitation of the photosensitizers, further amplified by the heavy-atom effect in InPc derivatives. Quantum Chemistry calculations reveal how electronically excited states and enhanced spin-orbit coupling promote efficient intersystem crossing and singlet oxygen formation in zinc(II) and indium(III) phthalocyanines. The in vitro sono-photodynamic potential of the phthalocyanine derivatives 3a and 4a was assessed in MCF-7 and MDA-MB-231 breast cancer cells. In both lines, SPDT significantly reduced cell viability while elevating intracellular ROS levels and apoptotic cell populations. Remarkably, the combined SPDT treatment elicited stronger cytotoxic and oxidative stress responses than either SDT or PDT alone. Furthermore, SPDT activated inflammasome-related pathways, as indicated by increased caspase-1 activity and higher release of pro-inflammatory cytokines. These findings highlight the enhanced efficacy of SPDT over single-modality therapies and underscore the promising potential of phthalocyanine-based 3a and 4a as sonophotodynamic sensitizers for breast cancer.

PMID:
42627930
Bibliographic data and abstract were imported from PubMed on 22 Aug 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.