| Autor: |
Kadhim A; Department of Chemistry , University of Sheffield , Sheffield S3 7HF , U.K., McKenzie LK; Department of Chemistry , University of Sheffield , Sheffield S3 7HF , U.K.; Department of Oncology and Metabolism , University of Sheffield , Sheffield S10 2RX , U.K., Bryant HE; Department of Oncology and Metabolism , University of Sheffield , Sheffield S10 2RX , U.K., Twyman LJ; Department of Chemistry , University of Sheffield , Sheffield S3 7HF , U.K. |
| Jazyk: |
angličtina |
| Zdroj: |
Molecular pharmaceutics [Mol Pharm] 2019 Mar 04; Vol. 16 (3), pp. 1132-1139. Date of Electronic Publication: 2019 Feb 12. |
| DOI: |
10.1021/acs.molpharmaceut.8b01119 |
| Abstrakt: |
Macromolecules are potentially useful delivery systems for cancer drugs, as their size allows them to utilize the enhanced permeability and retention effect (EPR), which facilitates selective delivery to (and retention within) tumors. In addition, macromolecular delivery systems can prolong circulation times as well as protect and solubilize toxic and hydrophobic drug moieties. Overall, these properties and abilities can result in an enhanced therapeutic effect. Photodynamic therapy (PDT) combines the use of oxygen and a photosensitizer (PS), which become toxic upon light irradiation. We proposed that a PS encapsulated within a water-soluble macromolecule could exploit the EPR effect and safely and selectively deliver the PS to a tumor. In this paper, we describe the synthesis of a porphyrin-cored hyperbranched polymer that aggregated into larger micellar structures. DLS and TEM indicated that these aggregated structures had diameters of 45 and 20 nm for the solvated and nonsolvated species, respectively. The porphyrin-cored HBP (PC-HBP), along with the nonencapsulated porphyrin (THPP), were screened against EJ bladder carcinoma cells in the dark and light. Both THPP and PC-HBP displayed good toxicity in the light, with LD50 concentrations of 0.5 and 1.7 μM, respectively. However, in the dark, the nonincorporated porphyrin (THPP) displayed significant toxicity, generating an LD50 of 4 μM. On the other hand, no dark toxicity was observed for the polymer system (PC-HBP) at concentrations of 100 μM or less. As such, incorporation within the large polymer aggregate serves to eliminate dark toxicity while maintaining excellent toxicity when irradiated. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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