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

Repetowski P., Warszynska M., Kostecka A., Pucelik B., Barzowska A., EMAMI A., ...Daha Fazla

ACS APPLIED MATERIALS & INTERFACES, cilt.16, sa.37, ss.48937-48954, 2024 (SCI-Expanded, Scopus)

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 16 Sayı: 37
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1021/acsami.4c04138
  • Dergi Adı: ACS APPLIED MATERIALS & INTERFACES
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, Compendex, EMBASE, INSPEC, MEDLINE
  • Sayfa Sayıları: ss.48937-48954
  • Anahtar Kelimeler: advanced cellular models, anticancer activity, organoids, photodynamic therapy (PDT), phthalocyanines, reactive oxygen species (ROS), vascular-targeted photodynamic therapy (V-PDT)
  • Acıbadem Mehmet Ali Aydınlar Üniversitesi Adresli: Evet

Özet

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(2)tBu demonstrated an outstanding ability to generate singlet oxygen (Phi(Delta) = 0.87-0.99), while ZnSO(2)tBu in addition to O-1(2) (Phi(Delta) = 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-ow) 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(2)tBu and 100% of PtSO(2)tBu-treated mice, and no recurrence has so far been observed for up to five months after treatment. In the case of PtSO(2)tBu, the effect was significantly stronger, offering a wider range of light doses suitable for achieving effective PDT.