Covalent Organic Polymer as a Carborane Carrier for Imaging-Facilitated Boron Neutron Capture Therapy

Abstract

Boron neutron capture therapy (BNCT) is an atomic targeted radiotherapy that shows fantastic suppression impact on locally intrusive threatening tumors. One key factor for effective BNCT is to aggregate an adequate concentration (>20 ppm) of 10 B in the cytoplasm of the tumor. Carborane-loaded polymer nanoparticles are promising because of their outstanding biocompatibility and plasma steadiness. In this study, a new class of carborane-loaded nanoscale covalent organic polymers (BCOPs) was prepared by a Schiff base condensation reaction, and their solubility was greatly improved in common solvents via alkyl chain engineering and size tailoring. The obtained BCOP-5T was further functionalized by biocompatible 1,2-distearoyl-snglycero-3-phosphoethanolamine-N-[amino(polyethylene-glycol)-2000] (DSPE-PEG, molecular weight 2000) to form stable aqueous-phase nanoparticles with a hydrodynamic diameter of around 100 nm. After chelating with radioactive copper-64, DSPE-BCOP-5T was tracked by positron emission tomography (PET) imaging and showed significant accumulation in the tumor. DSPE-BCOP-5T + neutron radiation showed remarkable tumor suppression in 4T1 tumor-bearing mice (murine breast cancer). No obvious physical tissue damage and abnormal behavior were observed, demonstrating that the boron delivery was successful and tumor-selective. To conclude, this study presents a theranostic COP-based platform with a well-defined composition, good biocompatibility, and satisfactory tumor accumulation, which is promising for PET imaging, drug delivery, and BNCT.

Guanidinium‐Based Ionic Covalent Organic Porous Polymer as Natamycin Delivery Agents for Anti‐Candida albicans

“…Initially, the ICOP was prepared thorough the copolymerization of 4,4'-diselanediyldibenzaldehyde (BiSe) and Triaminoguanidine hydrochloride (TG) via the catalyst-free Schiff base chemistry. [24] And the NAT-ICOP was prepared via a physical absorption method. The complex was easily separated by filtration which was subsequently washed with DMSO and water, and dried at room temperature.…”

“…As seen from Figure 1, the NAT‐ICOP composite drug delivery system was prepared via a two‐step method. Initially, the ICOP was prepared thorough the copolymerization of 4,4′‐diselanediyldibenzaldehyde (BiSe) and Triaminoguanidine hydrochloride (TG) via the catalyst‐free Schiff base chemistry [24] . And the NAT‐ICOP was prepared via a physical absorption method.…”

Carboranes as unique pharmacophores in antitumor medicinal chemistry

“…Among the nanoscale boron carriers, the carborane-loaded nanoscale covalent organic polymers (BCOPs) and magnetic nanoparticles are effective carriers in the BNCT. 58 , 59 , 60 , 61 , 62 Multifunctional BCOPs were prepared from a Schiff base condensation reaction and further functionalized into BCOP-5T (five octyl chains) through alkyl chain engineering and size adjustment. 58 With the loading of carborane, the 1,2-distearoyl- sn -glycero-3-phosphoethanolamine-N-[amino-(polyethyleneglycol)-2000] (M w = 2000) coated with BCOP-5T exhibits excellent physiological stability and biocompatibility, and has been used as a carborane-loaded nanocarrier in BNCT.…”

“… 58 , 59 , 60 , 61 , 62 Multifunctional BCOPs were prepared from a Schiff base condensation reaction and further functionalized into BCOP-5T (five octyl chains) through alkyl chain engineering and size adjustment. 58 With the loading of carborane, the 1,2-distearoyl- sn -glycero-3-phosphoethanolamine-N-[amino-(polyethyleneglycol)-2000] (M w = 2000) coated with BCOP-5T exhibits excellent physiological stability and biocompatibility, and has been used as a carborane-loaded nanocarrier in BNCT. 58 Hosmane and co-workers showed that through the click reaction, the carborane cage was successfully adsorbed into the modified magnetic nanoparticles ( 4 ) ( Figure 3 D).…”

Semiconducting Polymer Nano-Radiopharmaceutical For Combined Radio-Photothermal Therapy of Pancreatic Tumor

“…Semiconducting polymer nanoparticles (SPNs) composed of completely organic compounds have been emerged as photothermal agents for tumor therapy [26][27][28][29]. Compared with other inorganic nanomaterials such as gold nanorods and carbon nanotubes, SPNs possess unique characteristics such as better biocompatibility, higher NIR absorption and photothermal conversion e ciency, feasibility and controllability [30][31][32]. In particular, SPNs not only allow for convenient chemical engineering of backbones and side chains for on-demand functionalization, but also are conducive to nanoengineering to achieve size or morphology controllability [33].To date, the utilization of SPNs for PTT has been fully explored, but combined therapy are rarely reported [10,34,35].…”