Methotrexate-coupled nanoparticles and magnetic nanochemothermia for the relapse-free treatment of T24 bladder tumors

Abstract

Heat-based approaches have been considered as promising tools due to their ability to directly eradicate tumor cells and/or increase the sensitivity of tumors to radiation- or chemotherapy. In particular, the heating of magnetic nanoparticles (MNPs) via an alternating magnetic field can provide a handy alternative for a localized tumor treatment. To amplify the efficacy of magnetically induced thermal treatments, we elucidated the superior tumor-destructive effect of methotrexate-coupled MNPs (MTX/MNPs) in combination with magnetic heating (nanochemothermia) over the thermal treatment alone. Our studies in a murine bladder xenograft model revealed the enormous potential of nanochemothermia for a localized and relapse-free destruction of tumors which was superior to the thermal treatment alone. Nanochemothermia remarkably fostered the reduction of tumor volume. It impaired proapoptotic signaling (eg, p-p53), cell survival (eg, p-ERK1/2), and cell cycle (cyclins) pathways. Additionally, heat shock proteins (eg, HSP70) were remarkably affected. Moreover, nanochemothermia impaired the induction of angiogenic signaling by decreasing, for example, the levels of VEGF-R1 and MMP9, although an increasing tumor hypoxia was indicated by elevated Hif-1α levels. In contrast, tumor cells were able to recover after the thermal treatments alone. In conclusion, nanochemothermia on the basis of MTX/MNPs was superior to the thermal treatment due to a modification of cellular pathways, particularly those associated with the cellular survival and tumor vasculature. This allowed very efficient and relapse-free destruction of tumors.

Chemotherapeutic Drug Functionalized Nanoparticles are Beneficial When Treating Breast Cancer Via Magnetic Hyperthermia

“…After magnetic hyperthermia treatment, BT474 cells were allowed to grow for additionally 24 h or 48 h in cell culture flasks before they were harvested, washed and lysed with RIPA lysis buffer containing protease inhibitors as described previously [52].…”

“…in tumor tissue, blood count and protein expression. Tumor volume was monitored every three or four days as described elsewhere [52]. The assessment of temperature distribution within tumor area was determined as previously described [50].…”

Magnetic Nanoparticles Behavior in Biological Solutions; The Impact of Clustering Tendency on Sedimentation Velocity and Cell Uptake

“…Various techniques for characterization of MNPs and utilization, advantages, and disadvantages of biomedical applications of MNPs, such as imaging, magnetic hyperthermia, and drug delivery, have recently been adequately discussed in a review article [1]. Many researchers have investigated nanoparticles for their applications in drug delivery [2][3][4][5][6][7] as well as diagnostic imaging and treatment [8][9][10][11]. MNPs with superparamagnetic magnetization have been widely used in disease imaging techniques such as magnetic resonance imaging (MRI) [12][13][14][15].…”

“…This technique, known as hyperthermia, is usually used to kill tumor cells by raising the temperature up to 41-47 • C [16][17][18]. Several studies have presented promising results using the magnetic hyperthermia approach [4,5,19].…”

“…On the basis of the surface coating and reactive groups present, nanoparticles can be functionalized with various ligands or coupled to chemotherapeutics through covalent binding directly or with the aid of cross-linker molecules, electrostatically, or by encapsulation [5,[20][21][22]. Hence, many researchers have employed nanoparticles to develop a drug delivery system for chemotherapeutic drugs in order to reduce the toxic side effects of the free drugs on healthy tissues and organs during treatment [4,[23][24][25].…”