Chitosan Coating Effect on Cellular Uptake of PLGA Nanoparticles for Boron Neutron Capture Therapy

Abstract

Introduction Studies on boron neutron capture therapy BNCT have recently begun garnering attention. It is a cancer treatment method that exploits the nuclear reaction between boron and thermal neutrons, and is based on nuclear capture and fission reactions. Naturally occurring elemental boron has the following two stable isotopes: boron-10 10 B and boron-11 11 B. When 10 B is irradiated with low-energy thermal neutrons, it yields high linear energy transfer LET , α particles 4 He , and recoiling lithium-7 7 Li nuclei. The destructive effects of these high-energy particles are limited to boron-containing cells since the path length of high LET particles in tissue is limited 5-9 µm. Therefore, BNCT can theoretically kill tumor cells without affecting adjacent healthy cells if 10 B atoms can be selectively delivered and accumulated in the interstitial space of

Preparing (Metalla)carboranes for Nanomedicine

“…ICP-AES or ICP-MS are often used to quantify the amount of boron released from a carrier system, under specific conditions, as descriptor of drug leakage, sometimes coupled with a membrane or micropore dialysis pre-step. [43,178,186] UV/vis spectroscopy can also be used, [109] provided that a chromophore is present and accurate scattering correction to the measured absorbance is used. Olusanya et al (2019) recently used zeta potential and fluorescence spectroscopy to assess constitutional stability (zeta potential) of dipalmitoyl-phosphatidylcholine/1,2-distearol-snglycerol-3-phosphocholine (DPPC/DSPC) liposomal carriers, and loading stability via retention experiments of calcein (fluorescent dye) in PBS and human serum solutions.…”

“…[198,202a,b] Liposomal and polymeric formulations deserve specific attention, when translated to the application of (metalla)carboranes in medicine, since the use of liposomes and polymers (or copolymers) as nanosized drug delivery platforms is widely spread in the (metalla)carboranes literature, especially for applications in boron neutron capture therapy (BNCT), often justified by improved target selectivity, solubility properties and/or accumulation profiles. [43,108,119,138,146,149,150,178,185,186] It is particularly striking that the term "toxicity" is practically exclusively used to indicate the ability of the (metalla)carborane-based drug, with or without carrier, to promote cell death in the tumour cell line or tissue examined (acute toxicity), and is solely evaluated in terms of half-maximal inhibitory concentration (IC 50 ). A handful of examples exist, where IC 50 values were calculated for (metalla)carborane and borate compounds against model cell cultures for immune response, based on simple in vitro colorimetric assays, which will be briefly discussed below.…”

“…Leakage of covalently bonded 1‐(4‐vinylbenzyl)‐ closo ‐ ortho ‐carborane from core‐polymerised acetalated and methacryloylated poly(ethylene glycol)‐block‐poly‐(lactide) (acetal‐PEG‐ b ‐PLA‐MA) micelles in 10 wt% FBS solution was significantly suppressed, compared to analogous non‐crosslinked micelles, as determined by ICP‐AES. ICP‐AES or ICP‐MS are often used to quantify the amount of boron released from a carrier system, under specific conditions, as descriptor of drug leakage, sometimes coupled with a membrane or micropore dialysis pre‐step [43,178,186] . UV/vis spectroscopy can also be used, [109] provided that a chromophore is present and accurate scattering correction to the measured absorbance is used.…”

“…Complement‐activated pseudo ‐allergic reactions and adverse drug reactions (ADRs, e. g., hypersensitivity/allergic reactions) are the most recurrent side‐effects encountered in vivo after NPs′ administration, often reported as common side‐effects of liposomal and polymeric drug formulations, which might impair their therapeutic applicability [198,202a,b] . Liposomal and polymeric formulations deserve specific attention, when translated to the application of (metalla)carboranes in medicine, since the use of liposomes and polymers (or co‐polymers) as nanosized drug delivery platforms is widely spread in the (metalla)carboranes literature, especially for applications in boron neutron capture therapy (BNCT), often justified by improved target selectivity, solubility properties and/or accumulation profiles [43,108,119,138,146,149,150,178,185,186] . It is particularly striking that the term “toxicity” is practically exclusively used to indicate the ability of the (metalla)carborane‐based drug, with or without carrier, to promote cell death in the tumour cell line or tissue examined (acute toxicity), and is solely evaluated in terms of half‐maximal inhibitory concentration (IC 50 ).…”

Effect of the Conformation of Poly(L-lactide-<i>co</i>-glycolide) Molecules in Organic Solvents on Nanoparticle Size

“…In addition, surface modification is effective for improving the efficacy of nanoparticle preparation. However, this causes a change in particle size 11,12 . Therefore, to make the particle size uniform in a comparative experiment of various particles, it is necessary to carefully adjust the particle size when preparing the core nanoparticle.…”