In situ forming implants for local chemotherapy and hyperthermia of bone tumors

Abstract

Hyperthermia, an established adjuvant in cancer treatment, potentiates the effects of anticancer drugs and synergetic combination can be obtained improving the therapeutic outcome. Bone metastases may benefit from this combination when treated through in situ forming implants. Once loaded with magnetizable (nano-) particles and antineoplastic agents, these implants allow for the local application of magnetically-induced hyperthermia and the release of an anticancer drug. The implant can be heated applying an external magnetic field, sensitizing the surrounding tumoral tissues, while releasing the chemotherapeutic agent.Moreover, bone implants provide mechanical support to the weakened bone and consequently relieve pain.This review gives an overview of the current knowledge as well as the rationale of combining locally both magnetic hyperthermia and chemotherapy using in situ forming implants in the field of bone metastases treatment. KeywordsInduced hyperthermia, chemotherapy, drug delivery systems, in situ forming implants, iron oxide nanoparticles, bone metastases, cementoplasty, vertebroplasty 3

PMMA-Fe 3 O 4 for internal mechanical support and magnetic thermal ablation of bone tumors

“…It has been reported that irreversible cellular damage occurs when heating tissues at 43 °C for several hours, and cell death arises with continuous heat for 4-6 min at 50-55 °C. When the temperature reaches 60-100 °C, tissue coagulation occurs nearly immediately, while at temperatures greater than 100 °C, tissue becomes vaporized and carbonized 47-50. Our results are consistent with the literature, and our target temperature is greater than 60 °C, which can effectively and quickly induce tumor necrosis and stimulate the immune system through the expression of heat shock proteins (HSPs).…”

PMMA-Fe 3 O 4 for internal mechanical support and magnetic thermal ablation of bone tumors

“…It has been reported that irreversible cellular damage occurs when heating tissues at 43 °C for several hours, and cell death arises with continuous heat for 4-6 min at 50-55 °C. When the temperature reaches 60-100 °C, tissue coagulation occurs nearly immediately, while at temperatures greater than 100 °C, tissue becomes vaporized and carbonized 47-50. Our results are consistent with the literature, and our target temperature is greater than 60 °C, which can effectively and quickly induce tumor necrosis and stimulate the immune system through the expression of heat shock proteins (HSPs).…”

Magnetic Hyperthermia Ablation of Tumors Using Injectable Fe3O4/Calcium Phosphate Cement

“…The injectability study showed the injectable percentage of the 10% MCPC was 90.68 ± 0.92%, which guaranteed the local injection of the MCPC in a minimally invasive manner. The exotherm during the setting reaction was considerably low for the 10% MCPC, which was 1.36 ± 0.14 °C and should be much safer than PMMA, which has a much higher exotherm of 95 °C in polymerization . The degradability test showed that the MCPC was degraded with time.…”

“…The reason might owe to the heterogeneity between tumor tissue and excised bovine liver tissue, which leads to a nonuniform response to heat treatment. The tumor cells were reported to be more sensitive to heat than the normal cells; thus, the tumor tissue could be completely ablated in a shorter time and lower temperature …”

“…The exotherm during the setting reaction was considerably low for the 10% MCPC, which was 1.36 ± 0.14 °C and should be much safer than PMMA, which has a much higher exotherm of 95 °C in polymerization. 29 The degradability test showed that the MCPC was degraded with time. The in vitro magnetic heating efficiency study showed that the MCPC could quickly heat the PBS and the excised bovine liver under an alternating magnetic field, and the ablation efficiency increased with the time, the MCPC weight, and the iron content, which means the ablation volume is controllable.…”

“…The tumor cells were reported to be more sensitive to heat than the normal cells; thus, the tumor tissue could be completely ablated in a shorter time and lower temperature. 29 For the future clinical translation, the safety issue of MCPC has to be a concern, especially the degradability of the MCPC. Some research in the literature has shown that the CPC implant could be biodegraded in soft tissues.…”

PMMA-Fe 3 O 4 for internal mechanical support and magnetic thermal ablation of bone tumors

“…It has been reported that irreversible cellular damage occurs when heating tissues at 43 °C for several hours, and cell death arises with continuous heat for 4-6 min at 50-55 °C. When the temperature reaches 60-100 °C, tissue coagulation occurs nearly immediately, while at temperatures greater than 100 °C, tissue becomes vaporized and carbonized 47-50. Our results are consistent with the literature, and our target temperature is greater than 60 °C, which can effectively and quickly induce tumor necrosis and stimulate the immune system through the expression of heat shock proteins (HSPs).…”

Magnetic Hyperthermia Ablation of Tumors Using Injectable Fe3O4/Calcium Phosphate Cement

“…The injectability study showed the injectable percentage of the 10% MCPC was 90.68 ± 0.92%, which guaranteed the local injection of the MCPC in a minimally invasive manner. The exotherm during the setting reaction was considerably low for the 10% MCPC, which was 1.36 ± 0.14 °C and should be much safer than PMMA, which has a much higher exotherm of 95 °C in polymerization . The degradability test showed that the MCPC was degraded with time.…”

“…The reason might owe to the heterogeneity between tumor tissue and excised bovine liver tissue, which leads to a nonuniform response to heat treatment. The tumor cells were reported to be more sensitive to heat than the normal cells; thus, the tumor tissue could be completely ablated in a shorter time and lower temperature …”

“…The exotherm during the setting reaction was considerably low for the 10% MCPC, which was 1.36 ± 0.14 °C and should be much safer than PMMA, which has a much higher exotherm of 95 °C in polymerization. 29 The degradability test showed that the MCPC was degraded with time. The in vitro magnetic heating efficiency study showed that the MCPC could quickly heat the PBS and the excised bovine liver under an alternating magnetic field, and the ablation efficiency increased with the time, the MCPC weight, and the iron content, which means the ablation volume is controllable.…”

“…The tumor cells were reported to be more sensitive to heat than the normal cells; thus, the tumor tissue could be completely ablated in a shorter time and lower temperature. 29 For the future clinical translation, the safety issue of MCPC has to be a concern, especially the degradability of the MCPC. Some research in the literature has shown that the CPC implant could be biodegraded in soft tissues.…”

PMMA-Fe 3 O 4 for internal mechanical support and magnetic thermal ablation of bone tumors

“…It has been reported that irreversible cellular damage occurs when heating tissues at 43 °C for several hours, and cell death arises with continuous heat for 4-6 min at 50-55 °C. When the temperature reaches 60-100 °C, tissue coagulation occurs nearly immediately, while at temperatures greater than 100 °C, tissue becomes vaporized and carbonized 47-50. Our results are consistent with the literature, and our target temperature is greater than 60 °C, which can effectively and quickly induce tumor necrosis and stimulate the immune system through the expression of heat shock proteins (HSPs).…”

Magnetic Hyperthermia Ablation of Tumors Using Injectable Fe3O4/Calcium Phosphate Cement

“…The injectability study showed the injectable percentage of the 10% MCPC was 90.68 ± 0.92%, which guaranteed the local injection of the MCPC in a minimally invasive manner. The exotherm during the setting reaction was considerably low for the 10% MCPC, which was 1.36 ± 0.14 °C and should be much safer than PMMA, which has a much higher exotherm of 95 °C in polymerization . The degradability test showed that the MCPC was degraded with time.…”

“…The reason might owe to the heterogeneity between tumor tissue and excised bovine liver tissue, which leads to a nonuniform response to heat treatment. The tumor cells were reported to be more sensitive to heat than the normal cells; thus, the tumor tissue could be completely ablated in a shorter time and lower temperature …”

“…The exotherm during the setting reaction was considerably low for the 10% MCPC, which was 1.36 ± 0.14 °C and should be much safer than PMMA, which has a much higher exotherm of 95 °C in polymerization. 29 The degradability test showed that the MCPC was degraded with time. The in vitro magnetic heating efficiency study showed that the MCPC could quickly heat the PBS and the excised bovine liver under an alternating magnetic field, and the ablation efficiency increased with the time, the MCPC weight, and the iron content, which means the ablation volume is controllable.…”

“…The tumor cells were reported to be more sensitive to heat than the normal cells; thus, the tumor tissue could be completely ablated in a shorter time and lower temperature. 29 For the future clinical translation, the safety issue of MCPC has to be a concern, especially the degradability of the MCPC. Some research in the literature has shown that the CPC implant could be biodegraded in soft tissues.…”