Effect of radiotherapy and hyperthermia on the tumor accumulation of HPMA copolymer-based drug delivery systems.
Copolymers of N-(2-hydroxypropyl)methacrylamide (HPMA) are prototypic and well-characterized polymeric drug carriers that have been broadly implemented in the delivery of anticancer therapeutics. In an attempt to improve the tumor accumulation of HPMA copolymer-based drug delivery systems, their in vivo application was combined with radiotherapy and hyperthermia. As the effects of radiotherapy and hyperthermia were considered to depend significantly on the tumor model used, we first analyzed the accumulation of two differently sized HPMA copolymers in three different types of tumors, based on the syngeneic Dunning rat prostate carcinoma model. Subsequently, in these three models, the effects of different doses of radiotherapy and hyperthermia on the tumor accumulation of 31 kDa poly(HPMA), 65 kDa poly(HPMA) and 28 kDa poly(HPMA)-GFLG-doxorubicin were evaluated. It was found that the polymeric drug delivery systems accumulated effectively in all three tumor models. In addition, as opposed to hyperthermia, radiotherapy was found to improve the concentrations of the copolymers independent of the tumor model used. Based on these findings, we conclude that radiotherapy is an effective means for increasing the tumor accumulation of (polymeric) drug delivery systems, and we propose that the combination of carrier-based chemotherapy with radiotherapy holds significant potential for improving the treatment of advanced solid malignancies.
Lammers
Twan
T
Department of Innovative Cancer Diagnosis and Therapy, Clinical Cooperation Unit Radiotherapeutic Oncology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. T.Lammers@dkfz.de
Peschke
Peter
P
Kühnlein
Rainer
R
Subr
Vladimir
V
Ulbrich
Karel
K
Debus
Jürgen
J
Huber
Peter
P
Hennink
Wim
W
Storm
Gert
G
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D004337:Drug Carriers; D016503:Drug Delivery Systems; D006979:Hyperthermia, Induced; D007150:Immunohistochemistry; D007457:Iodine Radioisotopes; D008297:Male; D008689:Methacrylates; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy*; D011471:Prostatic Neoplasms / Q000188:drug therapy; D011878:Radiotherapy; D051381:Rats; D014018:Tissue Distribution
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D004337:Drug Carriers; D007457:Iodine Radioisotopes; D008689:Methacrylates; D004317:Doxorubicin; C032802:hydroxypropyl methacrylate