Frontiers in Boron-based Medicinal Chemistry

The following sections are included:

• Preface
• About the Editor
• Contents

Boron is a unique element with electron-deficient properties. In nature, it appears as boric acid and inorganic borates rather than in elemental form. Boron chemistry has been well developed, and a tremendous amount of new boron-containing compounds and materials have been reported. Consequently, boron has found a wide range of applications in fine chemistry, material science, new energy generation and drug development. In particular, boron-based small molecule drugs have attracted enormous attention in recent decades, of which some have been approved by the FDA for clinical use. As a result, boron-containing compounds have been employed in both chemotherapy and radiotherapy to treat different types of patients. Naturally, boron has two main isotopes, boron-11 and boron-10. Boron-10 is capable of absorbing thermal neutrons and initiating a nuclear fission reaction. The reaction generates and releases linear high-energy alpha (α) particles that can destroy tumor cells, so the concept has been utilized in boron neutron capture therapy and nuclear power plants, to treat cancer patients and reduce neutron leakage, respectively. Since the book aims to update and analyze advances in boron-based medicinal chemistry, this chapter first introduces basic boron chemistry and provides a brief overview of the clinical applications and perspectives of organoboron compounds typically involved in disease treatments.

Boron Neutron Capture Therapy (BNCT) is one of the most promising treatments among NCTs due to its long-term clinical application and unequivocal success in clinical trials. Nevertheless, current clinically used boronophenylalanine suffers from large uptake dose and low blood-to-tumor selectivity, and that initiated an overwhelming screening of next-generation BNCT drugs. Various boron agents, such as small molecules and macro/nano-vehicles, have been explored to greater success. In this chapter, different types of agents are rationally analyzed and compared, and the feasible targets are shared to present a perspective for the future of BNCT in cancer treatment.

Boron-conjugated polymers are the most promising of the polymeric systems studied, especially since some polymer–drug conjugate therapies like PEGylated Doxorubicin have previously been licensed. While more research and insights are required for the most part, some studies are quite encouraging, particularly in terms of clinical translatability. FDA has approved a variety of nanoparticle delivery routes, with an emphasis on the intravenous route, which has advantages in the treatment of metastasized tumors. Because of their biodegradable and biocompatible behavior inside the human body, polymeric nanoparticles are garnering increased interest for the treatment of malignant gliomas. Over the years, a wide range of drugs have been synthesized to improve boron administration for boron neutron capture therapy (BNCT). Numerous small molecules were synthesized from natural products that provided a better tumor-to-blood ratio of boron in the in vivo studies. In the same way, many macromolecules have been synthesized with various secondary functions. This chapter will describe some of the dendrimers and nanoparticles developed for BNCT.

Boron neutron capture therapy (BNCT) is a highly targeted, selective and effective technique to cure various types of cancers with reduced harm to the healthy cells. BNCT treatment needs to selectively and homogeneously distribute the ¹⁰boron (B) atoms inside the tumor tissues as well as capture sufficient neutrons to initiate a nuclear fission reaction with release of the high linear energy particles to kill the tumor cells. Similar to chemotherapy and other radiotherapies for tumor treatment, theranostics are vital in BNCT. Particularly, in vivo localization and quantification of ¹⁰B concentrations is critical for the success of BNCT. However, currently both instrumentation and technology do not fulfill accurate measurement and time requirements, so more effectual strategies are desired. This chapter summarizes the currently used diagnostic technologies in BNCT such as magnetic resonance imaging, positron emission tomography, and fluorescence imaging, and discusses emerging imaging techniques as well as boron carriers for BNCT application.

This chapter describes the development of boron neutron capture therapy (BNCT) from several technical aspects, including the neutron source, dosimetry and the treatment process. The principle of BNCT to kill tumor cells is mainly based on the nuclear reaction between thermal neutrons and boron. The energy generated by this nuclear reaction will destroy the double helix structure of DNA in the nucleus, making it impossible to repair and causing apoptosis of the whole cell. While the boron drug is the protagonist, the development and application of neutron sources and nuclear-related technologies are also a crucial aspect. The differences between the two types of neutron source, reactor-based and accelerator-based, as well as the key components and related technologies of these neutron sources are discussed. Three typical BNCT facilities in the world are also introduced. An entire section is dedicated to dosimetry, as accurate dose assessment and calculation are the key to the success of BNCT. The chapter is completed by a step-by-step explanation of the treatment planning system and treatment process.

The following section is included:

• Index