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Synthesis, Photo-Characterizations, and Pre-Clinical Studies on Advanced Cellular and Animal Models of Zinc(II) and Platinum(II) Sulfonyl-Substituted Phthalocyanines for Enhanced Vascular-Targeted Photodynamic Therapy.
- Source :
-
ACS applied materials & interfaces [ACS Appl Mater Interfaces] 2024 Sep 18; Vol. 16 (37), pp. 48937-48954. Date of Electronic Publication: 2024 Sep 06. - Publication Year :
- 2024
-
Abstract
- Two phthalocyanine derivatives tetra-peripherally substituted with tert -butylsulfonyl groups and coordinating either zinc(II) or platinum(II) ions have been synthesized and subsequently investigated in terms of their optical and photochemical properties, as well as biological activity in cellular, tissue-engineered, and animal models. Our research has revealed that both synthesized phthalocyanines are effective generators of reactive oxygen species (ROS). PtSO <subscript> 2 </subscript> t Bu demonstrated an outstanding ability to generate singlet oxygen (Φ <subscript>Δ</subscript> = 0.87-0.99), while ZnSO <subscript> 2 </subscript> t Bu in addition to <superscript>1</superscript> O <subscript>2</subscript> (Φ <subscript>Δ</subscript> = 0.45-0.48) generated efficiently other ROS, in particular ·OH. Considering future biomedical applications, the affinity of the tested phthalocyanines for biological membranes (partition coefficient; log P <subscript>ow</subscript> ) and their primary interaction with serum albumin were also determined. To facilitate their biological administration, a water-dispersible formulation of these phthalocyanines was developed using Pluronic triblock copolymers to prevent self-aggregation and improve their delivery to cancer cells and tissues. The results showed a significant increase in cellular uptake and phototoxicity when phthalocyanines were incorporated into the customizable polymeric micelles. Moreover, the improved distribution in the body and photodynamic efficacy of the encapsulated phthalocyanines were investigated in hiPSC-delivered organoids and BALB/c mice bearing CT26 tumors. Both photosensitizers exhibit strong antitumor activity. Notably, vascular-targeted photodynamic therapy (V-PDT) led to complete tumor eradication in 84% of ZnSO <subscript> 2 </subscript> t Bu and 100% of PtSO <subscript> 2 </subscript> t Bu- treated mice, and no recurrence has so far been observed for up to five months after treatment. In the case of PtSO <subscript>2</subscript> t Bu, the effect was significantly stronger, offering a wider range of light doses suitable for achieving effective PDT.
- Subjects :
- Animals
Humans
Mice
Platinum chemistry
Platinum pharmacology
Reactive Oxygen Species metabolism
Mice, Inbred BALB C
Cell Line, Tumor
Singlet Oxygen metabolism
Antineoplastic Agents chemistry
Antineoplastic Agents pharmacology
Antineoplastic Agents chemical synthesis
Photochemotherapy
Indoles chemistry
Indoles pharmacology
Isoindoles
Photosensitizing Agents chemistry
Photosensitizing Agents pharmacology
Photosensitizing Agents chemical synthesis
Zinc chemistry
Zinc pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1944-8252
- Volume :
- 16
- Issue :
- 37
- Database :
- MEDLINE
- Journal :
- ACS applied materials & interfaces
- Publication Type :
- Academic Journal
- Accession number :
- 39241197
- Full Text :
- https://doi.org/10.1021/acsami.4c04138