Local Delivery of Nimustine Hydrochloride against Brain Tumors: Basic Characterization Study

Area of Science:

• Neuro-oncology
• Drug Delivery Systems
• Immunotherapy

Background:

• Convection-enhanced delivery (CED) is a promising technique for direct tumor drug delivery.
• Clinical efficacy of CED is often limited by insufficient treatment outcomes.
• Nimustine hydrochloride (ACNU) is a water-soluble nitrosourea with potential for local delivery.

Purpose of the Study:

• To characterize the local distribution and clearance of nimustine hydrochloride (ACNU) after CED in the rodent brain.
• To investigate the effects of ACNU on the tumor microenvironment, specifically on immune-modulating factors.
• To evaluate the potential of ACNU as an agent for CED in intracranial tumors.

Main Methods:

• Mass spectrometry imaging to assess ACNU distribution in rodent brain post-CED.
• Radiolabeling (¹⁴C) to study ACNU clearance in the striatum.
• In vitro assessment of ACNU's effect on Fas and transforming growth factor-β1 (TGF-β1) secretion.
• Immunofluorescence to evaluate CD4/CD8 lymphocyte infiltration in xenografted intracranial tumors after ACNU-CED.

Main Results:

• ACNU demonstrated robust distribution in the rodent brain, comparable to hydrophilic dyes.
• Locally delivered ACNU persisted at the delivery site for over 24 hours.
• ACNU significantly inhibited TGF-β1 secretion and reduced Fas expression in vitro.
• CED of ACNU in intracranial tumors led to the infiltration of CD4/CD8 lymphocytes.

Conclusions:

• ACNU exhibits favorable distribution and delayed clearance characteristics when delivered via CED in the brain.
• Local ACNU delivery modulates the tumor microenvironment and promotes immune cell infiltration.
• ACNU is a promising candidate agent for convection-enhanced delivery strategies in treating brain tumors.