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.