Carborane Derivatives Loaded into Liposomes as Efficient Delivery Systems for Boron Neutron Capture Therapy

Abstract

Boron neutron capture therapy (BNCT) is an anticancer therapy based on the incorporation of (10)B in tumors, followed by neutron irradiation. Recently, the synthesis and delivery of new boronated compounds have been recognized as some of the main challenges in BNCT application. Here, we report on the use of liposomes as carriers for BNCT active compounds. Two carborane derivatives, i.e., o-closocarboranyl beta-lactoside (LCOB) and 1-methyl-o-closocarboranyl-2-hexylthioporphyrazine (H(2)PzCOB), were loaded into liposomes bearing different surface charges. The efficacy of these formulations was tested on model cell cultures, that is, DHD/K12/TRb rat colon carcinoma and B16-F10 murine melanoma. These induce liver and lung metastases, respectively, and are used to study the uptake of standard BNCT drugs, including borophenylalanine (BPA). Boron concentration in treated cells was measured by alpha spectrometry at the TRIGA mark II reactor (University of Pavia). Results showed high performance of the proposed formulations. In particular, the use of cationic liposomes increased the cellular concentration of (10)B by at least 30 times more than that achieved by BPA.

MRI‐Guided Neutron Capture Therapy by Use of a Dual Gadolinium/Boron Agent Targeted at Tumour Cells through Upregulated Low‐Density Lipoprotein Transporters

“…There are several examples of the use of nanosized carriers for the delivery of a high payload of NCT agents to tumour cells by using targeted liposomes. [22] Although liposomes show excellent delivery "in vitro" and the accumulation of 10 B-containing compounds at the targeted cells, they are effectively taken up "in vivo" by the reticulus endothelial system and circulating macrophages. As they are endogenous constituents of blood, LDL particles are relatively long circulating systems, are not so phagocitised by macrophages, and are therefore very suitable for targeting procedures.…”

Boron-Containing Phthalocyanines and Porphyrazines

“…[53][54][55][56] The synthesized highly hydrophobic porphyrazines were solubilized via loading into liposomes of different types and physicochemical properties of these lipids were studied. [54][55][56][57] To enchance water-solubility of the prepared porphyrazines the closo-carborane groups can be converted to the nido-carborane ones by the treatment with CsF followed by the Cs/K exchange to give the corresponding water-soluble boronated porphyrazines (Scheme 14). [53] More recently synthesis of the highly boronated porphyrazine 25 containing sixteen carborane fragments has been reported (Scheme 15).…”

A Facile Strategy for Constructing Boron‐Rich Polymer Nanoparticles via a Boronic Acid‐Related Reaction

“…The obtained boron-rich NPs have great application potential in boron neutron capture therapy (BNCT) for cancer treatment, since they can overcome the inherent drawbacks of small molecular BNCT agents, for example poor cellular uptake. [14] Furthermore, the boronate ester binding can offer the NPs improved stability and smaller size compared to non-covalent interactions. [11,12] …”