Solubilization of Poorly Soluble PDT Agent, Meso-tetraphenylporphin, in Plain or Immunotargeted PEG-PE Micelles Results in Dramatically Improved Cancer Cell Killing in Vitro

Overview

Journal Eur J Pharm Biopharm

Specialty Pharmacology

Date 2005 Dec 6

PMID 16326084

Citations 17

Authors

Aruna Roby

Suna Erdogan

Vladimir P Torchilin

Affiliations

Soon will be listed here.

Abstract

Poorly soluble photodynamic therapy (PDT) agent, meso-tetratphenylporphine (TPP), was effectively solubilized using non-targeted and tumor-targeted polymeric micelles prepared of polyethylene glycol/phosphatidyl ethanolamine conjugate (PEG-PE). Encapsulation of TPP into PEG-PE-based micelles and immunomicelles (bearing an anti-cancer monoclonal 2C5 antibody) resulted in significantly improved anticancer effects of the drug at PDT conditions against murine (LLC, B16) and human (MCF-7, BT20) cancer cells in vitro. For this purpose, the cells were incubated for 6 or 18 h with the TPP or TPP-loaded PEG-PE micelles/immunomicelles and then light-irradiated for 30 min. The phototoxic effect depended on the TPP concentration and specific targeting by immunomicelles. An increased level of apoptosis was shown in the PDT-treated cultures. The attachment of the anti-cancer 2C5 antibodies to TPP-loaded micelles provided the maximum level of cell killing at a given time. The results of this study showed that TPP-containing PEG-PE micelles may represent a useful formulation of the photosensitizer for practical PDT.

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References

Sibata M, Tedesco A, Marchetti J . Photophysicals and photochemicals studies of zinc(II) phthalocyanine in long time circulation micelles for photodynamic therapy use. Eur J Pharm Sci. 2004; 23(2):131-8. DOI: 10.1016/j.ejps.2004.06.004. View

Weishaupt K, Gomer C, Dougherty T . Identification of singlet oxygen as the cytotoxic agent in photoinactivation of a murine tumor. Cancer Res. 1976; 36(7 PT 1):2326-9. View

Ito T . Cellular and subcellular mechanisms of photodynamic action: the 1O2 hypothesis as a driving force in recent research. Photochem Photobiol. 1978; 28(4-5):493-508. DOI: 10.1111/j.1751-1097.1978.tb06957.x. View

Keene J, Kessel D, Land E, Redmond R, Truscott T . Direct detection of singlet oxygen sensitized by haematoporphyrin and related compounds. Photochem Photobiol. 1986; 43(2):117-20. DOI: 10.1111/j.1751-1097.1986.tb09501.x. View

Lukyanov A, Torchilin V . Micelles from lipid derivatives of water-soluble polymers as delivery systems for poorly soluble drugs. Adv Drug Deliv Rev. 2004; 56(9):1273-89. DOI: 10.1016/j.addr.2003.12.004. View

Bochaton-Piallat M, Gabbiani F, Redard M, Desmouliere A, Gabbiani G . Apoptosis participates in cellularity regulation during rat aortic intimal thickening. Am J Pathol. 1995; 146(5):1059-64. PMC: 1869281. View

Iakoubov L, Rokhlin O, Torchilin V . Anti-nuclear autoantibodies of the aged reactive against the surface of tumor but not normal cells. Immunol Lett. 1995; 47(1-2):147-9. DOI: 10.1016/0165-2478(95)00066-e. View

Statius van Eps R, LaMuraglia G . Photodynamic therapy inhibits transforming growth factor beta activity associated with vascular smooth muscle cell injury. J Vasc Surg. 1997; 25(6):1044-52; discussion 1052-3. DOI: 10.1016/s0741-5214(97)70128-9. View

Hadjur C, Wagnieres G, Ihringer F, Monnier P, van den Bergh H . Production of the free radicals O2.- and .OH by irradiation of the photosensitizer zinc(II) phthalocyanine. J Photochem Photobiol B. 1997; 38(2-3):196-202. DOI: 10.1016/s1011-1344(96)07440-4. View

10.

Statius van Eps R, Adili F, LaMuraglia G . Photodynamic therapy inactivates cell-associated basic fibroblast growth factor: a silent way of vascular smooth muscle cell eradication. Cardiovasc Res. 1997; 35(2):334-40. DOI: 10.1016/s0008-6363(97)00120-x. View

11.

Iakoubov L, Torchilin V . A novel class of antitumor antibodies: nucleosome-restricted antinuclear autoantibodies (ANA) from healthy aged nonautoimmune mice. Oncol Res. 1997; 9(8):439-46. View

12.

Dougherty T, Gomer C, Henderson B, Jori G, Kessel D, Korbelik M . Photodynamic therapy. J Natl Cancer Inst. 1998; 90(12):889-905. PMC: 4592754. DOI: 10.1093/jnci/90.12.889. View

13.

Iakoubov L, Torchilin V . Nucleosome-releasing treatment makes surviving tumor cells better targets for nucleosome-specific anticancer antibodies. Cancer Detect Prev. 1998; 22(5):470-5. DOI: 10.1046/j.1525-1500.1998.00055.x. View

14.

MCCAUGHAN Jr J . Photodynamic therapy: a review. Drugs Aging. 1999; 15(1):49-68. DOI: 10.2165/00002512-199915010-00005. View

15.

Torchilin V, Rammohan R, Weissig V, Levchenko T . TAT peptide on the surface of liposomes affords their efficient intracellular delivery even at low temperature and in the presence of metabolic inhibitors. Proc Natl Acad Sci U S A. 2001; 98(15):8786-91. PMC: 37513. DOI: 10.1073/pnas.151247498. View

16.

Morgan J, Oseroff A . Mitochondria-based photodynamic anti-cancer therapy. Adv Drug Deliv Rev. 2001; 49(1-2):71-86. DOI: 10.1016/s0169-409x(01)00126-0. View

17.

Torchilin V, Levchenko T, Lukyanov A, Khaw B, Klibanov A, Rammohan R . p-Nitrophenylcarbonyl-PEG-PE-liposomes: fast and simple attachment of specific ligands, including monoclonal antibodies, to distal ends of PEG chains via p-nitrophenylcarbonyl groups. Biochim Biophys Acta. 2001; 1511(2):397-411. DOI: 10.1016/s0005-2728(01)00165-7. View

18.

Schmidt-Erfurth U, Hasan T . Mechanisms of action of photodynamic therapy with verteporfin for the treatment of age-related macular degeneration. Surv Ophthalmol. 2000; 45(3):195-214. DOI: 10.1016/s0039-6257(00)00158-2. View

19.

Maeda H, Wu J, Sawa T, Matsumura Y, Hori K . Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Control Release. 2000; 65(1-2):271-84. DOI: 10.1016/s0168-3659(99)00248-5. View

20.

Statius van Eps R, Mark L, Schiereck J, LaMuraglia G . Photodynamic therapy inhibits the injury-induced fibrotic response of vascular smooth muscle cells. Eur J Vasc Endovasc Surg. 1999; 18(5):417-23. DOI: 10.1053/ejvs.1999.0911. View