# Liposome-Encapsulated Carfilzomib as a Radiosensitizer in Solid Tumors

## TL;DR

This study shows that liposome-encapsulated carfilzomib improves radiation therapy effectiveness in solid tumors by disrupting DNA repair.

## Contribution

A novel liposomal formulation of carfilzomib is developed as a radiosensitizer with improved solubility and tumor-specific effects.

## Key findings

- CFZ-loaded liposomes reduced clonogenic survival and impaired DNA repair in breast cancer cells.
- Local administration of CFZ followed by radiation suppressed primary tumor growth without systemic toxicity.
- The combination treatment reduced pulmonary metastatic burden compared to controls.

## Abstract

Chemoradiotherapy
is a common treatment option for many
cancers.
Carfilzomib (CFZ) is an effective chemotherapeutic drug with a multitude
of cellular effects. However, CFZ has yet to be studied in the context
of chemoradiotherapy. To study the application of CFZ in chemoradiotherapy,
we synthesized CFZ-loaded liposomes. We report a novel liposomal formulation
of the proteasome inhibitor CFZ designed to enhance tumor radiosensitivity
while improving drug solubility and tolerability. CFZ-loaded PEGylated
liposomes were synthesized via thin-film hydration and probe sonication,
achieving an average diameter of ∼127 nm and an encapsulation
efficiency of 64%. In murine 4T1 breast carcinoma cells, CFZ treatment
prior to irradiation significantly reduced clonogenic survival (dose
enhancement factor = 1.26) and increased γ-H2AX foci retention,
indicating impaired DNA double-strand break repair. In a dual-flank
Balb/cJ allograft model, local intratumoral administration of CFZ
followed by ionizing radiation (8 Gy × 2) markedly suppressed
primary tumor growth compared with monotherapies without inducing
systemic toxicity. Although a strong abscopal effect on distant tumors
was not observed, the combination treatment reduced the pulmonary
metastatic burden relative to controls. Collectively, these results
demonstrate that liposomal carfilzomib can act as an effective radiosensitizer,
functioning through perturbation of DNA repair and modulation of the
tumor response to radiation. This study highlights a translationally
relevant nanotherapeutic approach for enhancing chemoradiotherapy
outcomes in solid malignancies.