Biodistribution and antitumour efficacy of long-circulating N-(2-hydroxypropyl)methacrylamide copolymer–doxorubicin conjugates in nude mice

Noninvasive Optical Imaging of Nanomedicine Biodistribution

“…As can be clearly seen, 3D CT-FMT realistically depicted probe accumulation in liver, kidney and bladder. Both absolute (%ID) and relative (organs-to-organ) values were relatively well in line with those reported in the literature for radiolabeled polymeric nanomedicines 12,34,[36][37][38][39] . Furthermore, as for tumors ( Figure 5), also the time-dependent trends in liver, kidney and bladder accumulation were in line with previous studies, with liver remaining relatively constant over time, and kidney and bladder decreasing 12,34,36 .…”

“…Taking previous results obtained with regard to the biodistribution of radiolabeled HPMA-based polymeric drug carriers into account, 12,34,[36][37][38][39] however, also 3D FMT did not properly reflect tumor and healthy organ accumulation. As exemplified by the lower panels in Figure 2B, apart from significant accumulation in tumors and some residual signal that could be allocated to the heart (i.e.…”

Prodrug Strategies in Anticancer Chemotherapy

“…As a negative result, PK1 does not display optimal tumor targeting: Cross-linked high-molecular-weight homologues of PK1 with molecular weights ranging from 22-1230 kDa were synthesized by Kopecek et al with the aim of enhancing the circulatory retention. [244,245] To circumvent accumulation in various organs of the body, enzymatically cleavable cross-links were incorporated in the architecture of the polymer which render the polymer biodegradable. After evaluating the body distribution of the cross-linked HPMA copolymerdoxorubicin conjugates, Kopecek et al found that the half-life of a 1230-kDa conjugate in the blood was 5-fold higher than for a 22-kDa conjugate.…”

Sequential combination therapy of ovarian cancer with degradable N -(2-hydroxypropyl)methacrylamide copolymer paclitaxel and gemcitabine conjugates

“…Consequently, tumors were not exposed to effective drug concentrations. For prolonged plasma circulation and enhanced tumor accumulation, it is imperative to use polymeric carriers with increased Mw, which makes high-Mw biodegradable polymeric conjugates the most attractive candidates for future clinical applications (8,9). Thus, we designed second-generation HPMA copolymer carriers that contain enzymatically degradable oligopeptide sequences in the linear main chain by combining reversible addition-fragmentation chain transfer (RAFT) polymerization and click reactions (10)(11)(12).…”