Photosensitizer targeting in photodynamic therapy II. Conjugates of haematoporphyrin with serum lipoproteins

Hamblin, Michael R.; Newman, E. L.

doi:10.1016/1011-1344(94)07036-9

Cited by 84 publications

(55 citation statements)

References 50 publications

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“…If the cationic conjugates are taken up by i.p. tumour cells via endocytosis and degraded in lysosomes where the 1251 was released and the ce6 retained, this would explain the higher tumour to normal ratios of ce6 compared with 1251, and would also be consistent with in vitro data using these OC125F(ab)2 PICs (Hamblin et al, 1996) and previous work using conjugates between'251 labelled low-density lipoprotein and haematoporphyrin (Hamblin and Newman, 1994). The high ratios but low absolute content of ce6 found for the cationic and anionic rabbit IgG PICs are also consistent with this hypothesis.…”

Section: Discussionsupporting

confidence: 77%

Biodistribution of charged F(ab')2 photoimmunoconjugates in a xenograft model of ovarian cancer

Duska

Hamblin²,

Bamberg³

et al. 1997

Br J Cancer

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Summary The effect of charge modification of photoimmunoconjugates (PICs) on their biodistribution in a xenograft model of ovarian cancer was investigated. Chlorin.6 e6 was attached site specifically to the F(ab')2 fragment of the murine monoclonal antibody OC125, directed against human ovarian cancer cells, via poly-1-lysine linkers carrying cationic or anionic charges. Preservation of immunoreactivity was checked by enzyme-linked immunosorbent assay (ELISA). PICs were radiolabelled with 1251 and compared with non-specific rabbit IgG PICs after intraperitoneal (i.p.) injection into nude mice. Samples were taken from normal organs and tumour at 3 h and 24 h. Tumour to normal 1251 ratios showed that the cationic OC1 25F(ab')2 PIC had the highest tumour selectivity. Ratios for ce6 were uniformly higher than for 1251, indicating that ce6 became separated from 1251. OC1 25F(ab')2 gave highest tissue values of 1251, followed by cationic OC1 25F(ab')2 PIC; other species were much lower. The amounts of cee delivered per gram of tumour were much higher for cationic OC125F(ab')2 PIC than for other species. The results indicate that cationic charge stimulates the endocytosis and lysosomal degradation of the OC1 25F(ab')2-pl-cee that has bound to the i.p. tumour. Positively charged PICs may have applications in the i.p. photoimmunotherapy of minimal residual ovarian cancer.

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Section: Discussionsupporting

confidence: 77%

Biodistribution of charged F(ab')2 photoimmunoconjugates in a xenograft model of ovarian cancer

Duska

Hamblin²,

Bamberg³

et al. 1997

Br J Cancer

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“…However, covalently linked LDL-PS conjugates have rarely been used in PDT. There has been one report of covalent conjugates between LDL and the PS haematoporphyrin (Hamblin and Newman, 1994). These authors found that LDL-HP showed some apoB/E receptor-mediated uptake in HT29 colorectal tumour cells and in fibroblasts, but a dramatic increase in uptake via the apoB/E receptor-mediated phagocytosis pathway, which is characteristic of macrophage-type cells (Suits et al, 1989).…”

mentioning

confidence: 99%

“…Endothelial cells do not express the type I and II scavenger receptors (Itakura et al, 1993) found on macrophages, which recognize acetyl-LDL and highly oxidized LDL (Naito et al, 1992), but nevertheless their interaction with acetyl-LDL is well known (Voyta, 1984 (Hamblin and Newman, 1994) that complex formation between PS and LDL in vivo modifies the behaviour of the LDL (perhaps with some oxidative event), so that the PS-LDL complex behaves similarly to mildly oxidized LDL, being transcytosed by the tumour microvasculature endothelium and accumulated in tumour-associated macrophages. Allison et al (1994) found that the photosensitizer BPD-MA was better delivered to tumours in vivo associated with native LDL than with acetylated LDL.…”

Section: Photodynamic Targeting Using Ldl Conjugates 59mentioning

confidence: 99%

“…Better methods of localization in which sensitizers are combined with carriers that recognize the target tissue may therefore be useful in certain instances in order to increase the selective accumulation of the PS within the tumour (Jori, 1990;Hasan, 1992;Hamblin and Newman, 1994). Such delivery systems include monoclonal antibodies (MAbs) (Mew et al, 1983;Oseroff et al, 1986;Jiang et al, 1991), liposomes (Jori, 1990;Jori and Reddi, 1990), low-density lipoproteins (LDLs) (Mosley et al, 1981;Jori et al, 1984;SchmidtErfurth et al, 1994) and microspheres (Bachor et al,199 la).…”

mentioning

confidence: 99%

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Photodynamic targeting of human retinoblastoma cells using covalent low-density lipoprotein conjugates

Schmidt-Erfurth

Diddens²,

Birngruber³

et al. 1997

Br J Cancer

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“…These targeting species include monoclonal antibodies (Duska et al, 1997), lipoproteins (Hamblin and Newman, 1994b), microspheres (Bachor et al, 1991), liposomes (Cuomo et al, 1990) and polymers (Krinick et al, 1994). The latter may be either natural polymers such as dextran (Rakestraw et al, 1990) and polyamino-acids (Goff et al, 1991;Soukos et al, 1997) or synthetic polymers such as N-(2-hydroxypropyl)-methacrylamide (Seymour et al, 1987) and polyvinyl alcohol (Davis et al, 1993).…”

mentioning

confidence: 99%

In vivo fluorescence imaging of the transport of charged chlorin e6 conjugates in a rat orthotopic prostate tumour

et al. 1999

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Summary Polymeric drug conjugates are used in cancer therapy and, varying their molecular size and charge, will affect their in vivo transport and extravasation in tumours. Partitioning between tumour vasculature and tumour tissue will be of particular significance in the case of photosensitizer conjugates used in photodynamic therapy, where this partitioning can lead to different therapeutic effects. Poly-l-lysine chlorin e6 conjugates (derived from polymers of average M r 5000 and 25 000) were prepared both in a cationic state and by poly-succinylation in an anionic state. A fluorescence scanning laser microscope was used to follow the pharmacokinetics of these conjugates in vivo in an orthotopic rat prostate cancer model obtained with MatLyLu cells. Fluorescence was excited with the 454-528 nm group of lines of an argon laser and a 570 nm long pass filter used to isolate the emission. Results showed that the conjugates initially bound to the walls of the vasculature, before extravasating into the tissue, and eventually increasing in fluorescence. The anionic conjugates produced tissue fluorescence faster than the cationic ones, and surprisingly, the larger M r conjugates produced tissue fluorescence faster than the smaller ones with the same charge. These results are consistent with differences in aggregation state between conjugates.

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Photosensitizer targeting in photodynamic therapy II. Conjugates of haematoporphyrin with serum lipoproteins

Cited by 84 publications

References 50 publications

Biodistribution of charged F(ab')2 photoimmunoconjugates in a xenograft model of ovarian cancer

Biodistribution of charged F(ab')2 photoimmunoconjugates in a xenograft model of ovarian cancer

Photodynamic targeting of human retinoblastoma cells using covalent low-density lipoprotein conjugates

In vivo fluorescence imaging of the transport of charged chlorin e6 conjugates in a rat orthotopic prostate tumour

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