Intracellular uptake and behavior of two types zinc protoporphyrin (ZnPP) micelles, SMA-ZnPP and PEG-ZnPP as anticancer agents; unique intracellular disintegration of SMA micelles

HPMA Copolymer-Conjugated Pirarubicin in Multimodal Treatment of a Patient with Stage IV Prostate Cancer and Extensive Lung and Bone Metastases

“…We previously reported that vascular mediators such as nitroglycerin enhanced tumorselective drug delivery 2-to 3-fold in tumors in mice [3,4,21,22]. Nitrite compounds produce NO by converting NO 2 − to NO far more in hypoxic tumor tissues than in normoxic tissues [4,12,[21][22][23]. NO opens the endothelial cell-cell gap of blood vessels and increases the leakage of blood plasma and macromolecules into tumor tissues, as described earlier [3][4][5], thereby accomplishing augmentation of the EPR effect-driven drug delivery to tumors [3-9, 21, 22].…”

“…THP and the polymer are conjugated via a hydrazone bond, which liberates the free drug (THP) in acidic tumor environments [2]. Another advantage of THP is the cellular uptake rate: tumor cells incorporate free THP much more rapidly than they do other anthracyclines such as doxorubicin (DOX) and epirubicin, e.g., the rate is 30-100 times faster than that for DOX [2,5,12]. Many tumor cells have a highly upregulated cell membrane transporter system, i.e., nucleotide and glucose transporters, which appears applicable to pirarubicin, as opposed to other anthracyclines (e.g., DOX).…”

“…Many tumor cells have a highly upregulated cell membrane transporter system, i.e., nucleotide and glucose transporters, which appears applicable to pirarubicin, as opposed to other anthracyclines (e.g., DOX). However, in normal cells, this transporter system is not upregulated [5,12,13]. Thus far, this P-THP conjugate demonstrates many advantages.…”

HO-1/CO system in tumor growth, angiogenesis and metabolism — Targeting HO-1 as an anti-tumor therapy

“…Another possibility might be the use of styrene-maleic acid copolymermicelle-encapsulated ZnPP (SMA-ZnPP). In some studies the effectiveness of SMA-PEG was better and faster in comparison to PEG-ZnPP [125,126], however in ALL cells the results were similar and both compounds inhibited cell growth with comparable IC 50 values. What is more, those inhibitors synergized with other conventionally used drugs like imatinib in growth retardation in ALL cells [45].…”

Water soluble PEG-conjugate of xanthine oxidase inhibitor, PEG–AHPP micelles, as a novel therapeutic for ROS related inflammatory bowel diseases

“…And polymeric micelles could also be taken up by cells through endocytosis [49]. So we considered both mechanisms, i.e., reaching colon to exert therapeutic effect locally or entering the circulation through the intestine to exert therapeutic effect systemically may be involved in A C C E P T E D M A N U S C R I P T…”