Micelles of zinc protoporphyrin conjugated to N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer for imaging and light-induced antitumor effects in vivo

Hyaluronic Acid-zinc Protoporphyrin Conjugates for Photodynamic Antitumor Therapy

“…At 24 h after the intravenous administration of free ZnPP, ZnPP was accumulated in the spleen and much less in the tumor tissue, and mostly eliminated from the blood circulation ( Figure 4). Such poor pharmacokinetics of free ZnPP was also confirmed in our previous studies [7,13]. Tumor tissue possesses the leaky vasculature and lack the functional lymph vessel, therefore long-circulating biocompatible polymer gradually accumulate in the tumor by enhanced permeability and retention (EPR) effect [18].…”

“…We also reported that the cellular uptake of ZnPP decreased by conjugation to PEG and PHPMA [13,16]. Under physiological conditions, high molecular weight HA (≈1 × 10 6 ) is cleaved with hyaluronidase 2 into its fragments (≈1 × 10 4 ), and HA fragments produced are internalized by receptor-mediated endocytosis (CD44, RHAMM, LYVE-1 and HARE), and/or non-receptor mediated endocytosis (macro-pinocytosis) [17].…”

“…To overcome such drawbacks, we have reported water-soluble ZnPP derivatives using synthetic biocompatible polymers such as poly (styrene-co-maleic acid) (PSMA), poly(ethylene glycol) (PEG) and poly(N-(2-hydroxypropyl) methacrylamide) (PHPMA) [7,12,13]. These polymer conjugates of ZnPP derivatives were water-soluble, and were accumulated in the tumor tissue by EPR effect followed by tumor regression with or without light irradiation.…”

S-Nitrosated human serum albumin dimer as novel nano-EPR enhancer applied to macromolecular anti-tumor drugs such as micelles and liposomes

“…HPMA-ZnPP was prepared according to a previous report [22]. When the C26 tumors Asahi Spectra) at 400-800 nm (20 mW/cm 2 ) for 5 min as previously described [22].…”

pH-responsive metallo-supramolecular nanogel for synergistic chemo-photodynamic therapy

“…In particular, some metalloporphyrins, such as zinc-porphyrins, have been used as a kind of photosensitizer in clinical photodynamic therapy because of the effective generation of cytotoxic reactive oxygen species, such as singlet oxygen [16]. Several examples of dual effect combining the photodynamic action with a known therapeutic agent are reported [17][18][19][20].…”