# Targeted nano-boron based boron neutron capture therapy for glioma treatment

> **NIH NIH R21** · LOMA LINDA UNIVERSITY · 2024 · $158,828

## Abstract

Project Summary
Gliomas represent one of the most fatal and difficult to treat cancers. Despite the aggressive therapies,
including surgical resection, radiotherapy and chemotherapy the median survival time for patients remains very
poor. Boron neutron capture therapy (BNCT) is a noninvasive therapy for treating locally invasive malignant
tumors such as glioma. BNCT is a robust therapy with clear advantages as it relies on the nuclear capture and
fission reactions. Despite clear advantages, BNCT have not been as effective in the clinic due to inability to
achieve adequate amounts of Boron-10 (an active drug) concentration selectively in the target cancer cells,
which remains an unsolved problem. The studies proposed here are intended to fill a critical void using a
nanomedicine-based approach, which is uniquely poised to offer a solution to this unsolved problem. We have
developed nanodrugs for imaging and treatment of the primary and metastatic brain tumors. Here we propose
a novel nanodrug (Nano-10Boron), based on a natural, nontoxic and biodegradable polymer carrying in excess
of 300 molecules of Boron-10 enriched 4-boronophenylalanine (BPA) to cross blood-brain barrier (BBB) and
actively target and deliver high Bopron-10 concentration to glioma cells for effective BNCT. In Aim 1, we will
establish optimum functionating lead Nano-10Boron. This will be achieved by synthesizing next-generation
Nano-10Borons with varied loading of BPA and a tumor targeting and BBB transport peptide Angiopep-2 (Ap2).
In our preliminary studies, we used 12 Ap2 molecules and 300 BPA molecules covalently attached to PMLA
to form a first-generation Nano-10Boron. Our goal is to prepare a lead Nano-10Boron with maximum allowable
number of BPA molecules to enhance intracellular Boron-10 concentrations to boost the treatment outcome.
Aim 2 will focus on establishing an ideal time window for neutron flux irradiation for greater BNCT effect. PK
of our first-generation Nano-10Boron is about 1.44 h (see preliminary results for details) whereas, PK of free
BPA used in clinical studies ranges in few minutes. Additionally, PMLA based nanodrugs utilizes active
targeting and remains in tumor for relatively longer period, while clearing out from the systemic circulation
providing grater tumor uptake. Studies outlines in this aim will determine the optimum time window when we
have the highest Boron-10 concentrations in tumor vs surrounding healthy brain, facilitating effective BNCT
response while minimizing any potential off targeting toxicity to the healthy brain. Aim 3 will utilize the lead
Nano-10Boron to treat glioma baring mice to improve the survival. Lead Nano-10Boron will be injected at the
optimum dose developed in the previous aim followed by irradiation with low energy neutrons to treat glioma
baring animals and improve the survival time. The proposed work will solve the long-standing problem of
Boron-10 delivery, thereby making BNCT a practical therapy for glioma treatme...

## Key facts

- **NIH application ID:** 10600003
- **Project number:** 5R21CA259911-03
- **Recipient organization:** LOMA LINDA UNIVERSITY
- **Principal Investigator:** Rameshwar Tukaram Patil
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $158,828
- **Award type:** 5
- **Project period:** 2023-05-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10600003

## Citation

> US National Institutes of Health, RePORTER application 10600003, Targeted nano-boron based boron neutron capture therapy for glioma treatment (5R21CA259911-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10600003. Licensed CC0.

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