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Nature Communications Oct 2023Gadolinium (Gd)-coordinated texaphyrin (Gd-Tex) is a promising radiosensitizer that entered clinical trials, but temporarily fails largely due to insufficient...
Gadolinium (Gd)-coordinated texaphyrin (Gd-Tex) is a promising radiosensitizer that entered clinical trials, but temporarily fails largely due to insufficient radiosensitization efficacy. Little attention has been given to using nanovesicles to improve its efficacy. Herein, Gd-Tex is transformed into building blocks "Gd-Tex-lipids" to self-assemble nanovesicles called Gd-nanotexaphyrins (Gd-NTs), realizing high density packing of Gd-Tex in a single nanovesicle and achieving high Gd-Tex accumulation in tumors. To elucidate the impact of O concentration on Gd-Tex radiosensitization, myoglobin (Mb) is loaded into Gd-NTs (Mb@Gd-NTs), resulting in efficient relief of tumor hypoxia and significant enhancement of Gd-Tex radiosensitization, eventually inducing the obvious long-term antitumor immune memory to inhibit tumor recurrence. In addition to Gd, the versatile Mb@Gd-NTs can also chelate Lu (Mb@Lu/Gd-NTs), enabling SPECT/MRI dual-modality imaging for accurately monitoring drug delivery in real-time. This "one-for-all" nanoplatform with the capability of chelating various trivalent metal ions exhibits broad clinical application prospects in imaging-guided radiosensitization therapy.
Topics: Humans; Gadolinium; Myoglobin; Oxygen; Radiation-Sensitizing Agents; Neoplasms; Magnetic Resonance Imaging
PubMed: 37794000
DOI: 10.1038/s41467-023-41782-w -
European Journal of Medicinal Chemistry Mar 2024Radiotherapy (RT) stands as a cornerstone in the clinical armamentarium against various cancers due to its proven efficacy. However, the intrinsic radiation resistance... (Review)
Review
Radiotherapy (RT) stands as a cornerstone in the clinical armamentarium against various cancers due to its proven efficacy. However, the intrinsic radiation resistance exhibited by cancer cells, coupled with the adverse effects of RT on normal tissues, often compromises its therapeutic potential and leads to unwanted side effects. This comprehensive review aims to consolidate our understanding of how radiosensitizers inhibit the thioredoxin (Trx) system in cellular contexts. Notable radiosensitizers, including gold nanoparticles (GNPs), gold triethylphosphine cyanide ([Au(SCN) (PEt)]), auranofin, ceria nanoparticles (CONPs), curcumin and its derivatives, piperlongamide, indolequinone derivatives, micheliolide, motexafin gadolinium, and ethane selenide selenidazole derivatives (SeDs), are meticulously elucidated in terms of their applications in radiotherapy. In this review, the sensitization mechanisms and the current research progress of these radiosensitizers are discussed in detail, with the overall aim of providing valuable insights for the judicious application of Trx system inhibitors in the field of cancer radiosensitization therapy.
Topics: Humans; Gold; Metal Nanoparticles; Neoplasms; Radiation-Sensitizing Agents; Thioredoxins; Cyanates
PubMed: 38387331
DOI: 10.1016/j.ejmech.2024.116218 -
Discover Oncology Apr 2024Radiation therapy (RT) plays an important role in the treatment of glioblastoma multiforme (GBM). However, inherent intrinsic resistance of tumors to radiation, coupled...
PURPOSE
Radiation therapy (RT) plays an important role in the treatment of glioblastoma multiforme (GBM). However, inherent intrinsic resistance of tumors to radiation, coupled with the need to consider the tolerance of normal tissues and the potential effects on neurocognitive function, impose constraints on the amount of RT that can be safely delivered. A strategy for augmenting the effectiveness of RT involves the utilization of radiation sensitizers (RS). Directly implanting RS-loaded fibrin glue (FG) into the tumor resection cavity would by-pass the blood brain barrier, potentially enhancing the impact of RT on tumor recurrence. This study investigated the ability of FG to incorporate and release, in non-degraded form, the radiation sensitizers 5-Fluorouracil (5FU) and Motexafin gadolinium (MGd).
METHODS
FG layers were created in a 24-well plate by combining thrombin, fibrinogen, and 5FU or MGd. Supernatants from these layers were collected at various intervals and added to F98 glioma spheroid cultures in 96-well plates. Radiation was applied either before or after RS application as single or fractionated dosages. Spheroid growth was monitored for 14 days.
RESULTS
Combined treatment of FG-released 5FU and RT significantly inhibited spheroid growth compared to RS or RT as a single treatment. As a free drug, MGd demonstrated its efficacy in reducing spheroid volume, but had diminished potency as a released RS. Fractionated radiation was more effective than single dose radiation.
CONCLUSION
Non-degraded RS was released from the FG for up to 72 h. FG-released 5FU greatly increased the efficacy of radiation therapy.
PubMed: 38573401
DOI: 10.1007/s12672-024-00953-x