Boron neutron capture therapy is a low-invasive cancer therapy based on the neutron fission process that occurs upon thermal neutron irradiation of 10B-containing compounds; this process causes the release of alpha particles that selectively damage cancer cells. Although several clinical studies involving mercaptoundecahydro-closo-dodecaborate and the boronophenylalanine–fructose complex are currently ongoing, the success of this promising anticancer therapy is hampered by the lack of appropriate drug delivery systems to selectively carry therapeutic concentrations of boron atoms to cancer tissues, allowing prolonged boron retention therein and avoiding the damage of healthy tissues. To achieve these goals, numerous research groups have explored the possibility to formulate nanoparticulate systems for boron delivery. InHere this review wee researchers report the newest developments on boron vehiculating drug delivery systems based on nanoparticles, distinguished on the basis of the type of carrier used, with a specific focus on the formulation aspects.
Ref. | Functionalization for Targeting | B Derivative | Physical Features: Size/Drug Loading/Encapsulation Efficiency | Assays | BNCT Efficacy Assays |
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[46] |
Ref. | Functionalization for Targeting | B Derivative | Physical Features: Size/Drug Loading/Encapsulation Efficiency | Assays | BNCT Efficacy Assays | ||||||||||||||||||||||||||||||||||
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Na | 2 | B | 10 | H | 10 | ; Na | 2 | B | 12 | H | 11 | SH; Na | 2 | (n-B | 20 | H | 18 | ); Na | 2 | (i-B | 20 | H | 18 | ); K | 4 | B | 20 | H | 17 | 0H; Na | 3 | B | 20 | H | 19 | 43–70 nm/-/2–3% | Ex vivo: EMT6 mammary adenocarcinoma-bearing BALB/c mice | ||
Elemental Boron NPs | |||||||||||||||||||||||||||||||||||||||
[47] | K[ | nido | -7-CH | 3 | (CH | 2 | ) | 15 | -7,8-C | 2 | B | 9 | H | ll | ] | 42–114 nm/-/53–80% | |||||||||||||||||||||||
[65 | Ex vivo: EMT6 mammary adenocarcinoma-bearing BALB/c mice | ] | |||||||||||||||||||||||||||||||||||||
B | 5–15 nm/100%/- | In vivo: T98G human glioma cells | In vivo on cells: cell viability | [48] | Na | 3 | [1-(2′-B | 10 | H | 9 | )-2-NH | 3 | B | 10 | H | 8 | ] + K[ | nido | -7-CH | 3 | (CH | 2 | ) | 15 | -7,8-C | 2 | B | 9 | H | ll | ] | 57–114 nm/-/- | Ex vivo: EMT6 mammary adenocarcinoma-bearing BALB/c mice | ||||||
[66 | |||||||||||||||||||||||||||||||||||||||
] | B | 25–28 nm/-/- | In vivo: T98G, U87, and U251 human glioma cells | In vivo on cells: cell proliferation ability | [49][50] | ||||||||||||||||||||||||||||||||||
[67] | Na | 3 | [1-(2′-B | 10 | H | 9 | )-2-NH | 3 | B | 10 | H | 8 | ] + K[ | nido | -7-CH | 3 | (CH | 2 | ) | 15 | -7,8-C | 2 | B | 9 | H | 11 | ] | 109–134 nm/-/- | Ex vivo: EMT6 mammary adenocarcinoma-bearing BALB/c mice | ||||||||||
B | 37 nm/-/- | In vivo: HeLa cervical cancer cells | [51] | O | -closocarboranyl | β | -lactoside; 1-methyl- | Iron Oxide NPs | o | -carboranyl-2-hexylthioporphyrazine | 140–450 nm/-/- | In vitro: DHD/K12/TRb rat colon carcinoma and B16-F10 murine melanoma cells | |||||||||||||||||||||||||||
[52] | Internalizing-RGD | Doxorubicin conj. with 1-bromomethyl- | o | -carborane | 150–225 nm/-/- | In vitro: GL261 glioma cancer cells; in vivo: GL261-bearing C57BL/6 mice | In vivo and ex vivo on mice: survival curve and average weight change curve, histopathological analysis | ||||||||||||||||||||||||||||||||
[68] | Boron nitride | 10 nm/-/- | In vivo: MCF-7, MCF-10, and HeLa cells | [53] | BPA | -/-/- | |||||||||||||||||||||||||||||||||
[69] | [70] | ||||||||||||||||||||||||||||||||||||||
Carborane borate | 9–28 nm/11%/- | In vivo: mouse embryonic fibroblasts | [54] | BPA-fructose; BPA-fructose+BPA | 156–195 nm/-/52–82% | Ex vivo: liver metastases-induced BD-IX strain rats | |||||||||||||||||||||||||||||||||
[71][72] | |||||||||||||||||||||||||||||||||||||||
Isopropyl- | o | -carborane | 60 nm/15%/- | In vivo: HeLa, PC-3 (prostate cancer cell), HT-29 (colon cancer cell), BxPC-3 (pancreatic cancer cell), L929 (mouse subcutaneous adipose tissue cells) | [55] | BPA-fructose; 2-nitroimidazole derivative B-381 | |||||||||||||||||||||||||||||||||
[73] | 134–140 nm/1317–1801 ppb/4.5–5% | In vivo: bilateral D54 glioma-bearing athymic nude mice | |||||||||||||||||||||||||||||||||||||
M | -carboranylphosphinate and its acid form | 8–133 nm/-/- | In vivo: A172 glioblastoma and hCMEC/D3 endothelial cells; in vivo: mice | In vivo on cells: proliferation rate | [56] | BSH | 98–109 nm/-/2.5–3.4% | In vivo: male NIH-Swiss mice | |||||||||||||||||||||||||||||||
[57] | |||||||||||||||||||||||||||||||||||||||
[74] | B | 64 nm/9%/- | In vivo: L929 mouse fibroblasts, 4T1 mammary carcinoma and B16 melanoma cells, human peripheral blood mononuclear cells; ex vivo, in vivo: Balb/c male mice | Anti-human CEA monoclonal antibody | Cs | 210 | B | 12 | H | 11 | SH | ||||||||||||||||||||||||||||
[ | -/-/- | 75] | B | 15 nm/77%/-In vivo: AsPC-1 human pancreatic carcinoma cells; in vivo: AsPC-1-bearing male BALB/c nu/nu mice | |||||||||||||||||||||||||||||||||||
In vivo: U87 human glioblastoma and SW-620 human colorectal adenocarcinoma cells | [58] | Cs | 210 | B | 12 | H | 11 | SH | |||||||||||||||||||||||||||||||
[76 | -/-/ - | ] | In vivo: MRK nu/nu-1 human breast cancer cells | ||||||||||||||||||||||||||||||||||||
GdBO | 3 | 20–150 nm/-/- | [59] | Transferrin | BSH | 107–123 nm/26–30 µg/µmol lipid/6–8% | |||||||||||||||||||||||||||||||||
[77] | Folic acid | GdBO | In vivo: colon-26 mouse colon carcinoma cells; ex vivo: colon-26-bearing male BALB/c mice | 3 | 20–150 nm/2.5%/-In vivo on mice: survival and tumor growth rate | ||||||||||||||||||||||||||||||||||
In vivo: MIA-Pa-Ca-2 human pancreatic cancer, HeLa human cervical carcinoma and A549 human lung carcinoma cells | [60] | Rat or mouse anti-EGFR antibody | BSH | 130 nm/-/- | In vivo: U87 ΔEGFR, U87 WT and PAU87 human glioma cells; in vivo: U87 ΔEGFR-bearing BALB/c Slc-nu/nu mice | ||||||||||||||||||||||||||||||||||
[78] | 3-(Isopropyl- | o | -carboranyl) hydrindone | 110 nm/0.077 mg/g/- | In vivo: PC-3 prostate cancer epithelial cells, BxPC3 pancreatic cancer cells, MCF7 breast cancer cells, HepG2 and L929 murine fibroblast cells, and human skin fibroblasts | [61] | Closo | -dodecaborate lipids | |||||||||||||||||||||||||||||||
[ | 95–105 nm/-/- | 79] | Di( | o | -carborano-1,2-dimethyl)borateIn vivo: colon-26 mouse colorectal carcinoma cells; in vivo: colon-26-bearing female mice | In vivo on mice: tumor volume | |||||||||||||||||||||||||||||||||
386 nm/15.4%/- | In vivo: HepG2 cancer cells and human skin fibroblasts | [62] | BSH-encapsulating 10% distearoyl boron lipid | 127 nm/-/- | In vivo: colon-26-bearing female Balb/c mice | In vivo on mice: tumor volume | |||||||||||||||||||||||||||||||||
[80] | B | 180–280 nm/3.1 × 10 | 17 | atoms/mg/- | In vivo: T98G glioblastoma cells | [63] | BSH sodium and spermidinium salts, Na | 2 | [B | 12 | H | 12 | ], Na | 2 | [B | 12 | H | 11 | OH] and [B | 12 | H | 11 | NH | 3 | ] sodium and spermidinium salts | 100 nm/2635–13970 ppm/- | In vivo: colon-26 cells mouse colon carcinoma cells; in vivo: colon-26-bearing female mice | ||||||||||||
Gold NPs | [64] | BSH | 104–115 nm/-/2.5–46% | ||||||||||||||||||||||||||||||||||||
[ | |||||||||||||||||||||||||||||||||||||||
81 | |||||||||||||||||||||||||||||||||||||||
] | |||||||||||||||||||||||||||||||||||||||
1,2-Dicarba- | |||||||||||||||||||||||||||||||||||||||
closo | |||||||||||||||||||||||||||||||||||||||
-dodecaborane(12)-9-thiol (9SHOCB) and 1,2-dicarba- | |||||||||||||||||||||||||||||||||||||||
closo | |||||||||||||||||||||||||||||||||||||||
-dodecaborane(12)-9,12-dithiol (9,12SH-OCB) | |||||||||||||||||||||||||||||||||||||||
35–74 nm/-/- | |||||||||||||||||||||||||||||||||||||||
In vivo: UMR-106 rat osteogenic sarcoma cells | |||||||||||||||||||||||||||||||||||||||
[82] | Carborane derivative (NH | 2 | NH | 3 | ) | + | [7-NH | 2 | (CH | 2 | ) | 3 | S-7,8-C | 2 | B | 9 | H | 11 | ] | − | 9 nm/-/- | In vivo: HeLa, U87cells and L02 cells; in vivo: HeLa-xenografted nude mice | |||||||||||||||||
[83] | 123 | I-labeled anti-HER2 | Boron cage-SH | 58 nm/-/28–36% | In vivo: N87 human gastric cancer cells; in vivo: male NOD/SCID mouse | ||||||||||||||||||||||||||||||||||
[84] | Thiol B cage, BPA, or BPA fructose | 158–395 nm/-/3–35% | In vivo: N87 human gastric cancer male immunodeficient mouse | ||||||||||||||||||||||||||||||||||||
[85] | Trastuzumab (pretargeting agent) | Cobalt bis(dicarbollide) anion [3,3′-Co(C | 2 | B | 9 | H | 11 | ) | 2 | ] | − | 40 nm/195 µg/mg/- | In vivo: BT-474 breast cancer cells; in vivo: BT-474 breast cancer-bearing immunocompromised NOD/SCID mice | ||||||||||||||||||||||||||
[86] | Undecahydro- | closo | -dodecaborate (B | 12 | H | 12 | ) | 29 nm/0.307 µg B/mg of gold/- | In vivo: MCF-7 human mammary adenocarcinoma cells; in vivo: U87 glioma-bearing male SCID mice | ||||||||||||||||||||||||||||||
Silica NPs | |||||||||||||||||||||||||||||||||||||||
[87] | B | 64 nm/42%/- | |||||||||||||||||||||||||||||||||||||
[88] | RGD-K | B | 90 nm/-/- | In vivo: ALTS1C1 cells; in vivo: ALTS1C1-bearing mice | In vivo on cells: cell viability; ex vivo and in vivo on mice: tumor growth and mouse survival | ||||||||||||||||||||||||||||||||||
[89] | Amino-galactoside ligands | O | -carborane | -/445–539 µg/mg/- | In vivo: HepG2 liver cancer cells | In vivo on cells: colony formation | |||||||||||||||||||||||||||||||||
[90] | Activatable cell penetrating peptide | BSH | 200 nm/1.27%/- | In vivo: ALDH+ cancer stem cells sorted from CH-2879 chondrosarcoma cells; in vivo: BALB/c nu/nu male mice | In vivo on cells: DNA damage and clonogenic survival | ||||||||||||||||||||||||||||||||||
[91] | cRGD targeting pancreatic tumor sites overexpressing integrin receptors | O | -carborane | 136 nm/141.5 mg/g/- | In vivo: PANC-1 (human) and Panc-2 (mouse) cells; in vivo: female C57BL/6 mice | ||||||||||||||||||||||||||||||||||
[92] | BPA | 170 nm/2.5%/- | In vivo: OVCAR8 ovarian cancer cells, A549 lung cancer cells, FaDu head and neck cancer cells; | animal model | : CAM (chorioallantoic membrane) model transfected with human OVCAR8 ovarian cancer cells | ||||||||||||||||||||||||||||||||||
[93] | pH-(low)-insertion peptide | Boric acid | -/190 μg/g/- | In vivo: B16−F10 mouse melanoma and WEHI 164 mouse fibrosarcoma cells; ex vivo, in vivo: WEHI 164 tumor-bearing mice | In vivo on cells: cell viability; ex vivo and in vivo on mice: tumor growth | ||||||||||||||||||||||||||||||||||
Boron Carbide NPs and Quantum Dots | |||||||||||||||||||||||||||||||||||||||
[94][95] | TAT peptide | 284–459 nm/-/- | In vivo: B16 F10 mouse melanoma cells, B16-OVA cells; ex vivo, in vivo: B16-OVA-bearing C57BL/6J mice | ||||||||||||||||||||||||||||||||||||
[96] | Transferrin | 279 nm/-/- | In vivo: HeLa human cervical carcinoma and normal rat kidney epithelial cells; ex vivo: tumor-bearing mice | ||||||||||||||||||||||||||||||||||||
[97] | Human immunoglobulin G | 80 nm/-/- | In vivo: MC38 murine colon carcinoma and RAW 264.7 murine macrophages | ||||||||||||||||||||||||||||||||||||
[98] | 7 nm/-/- | In vivo: embryonic kidney HEK-293 cells, HeLa cervical cancer cells and human breast adenocarcinoma MCF-7 cells | |||||||||||||||||||||||||||||||||||||
[99] | Pretargeting with | trans | -cyclooctene modified trastuzumab | 7 nm/3.8%/- | In vivo: human BT-474 breast cancer cells; ex vivo, in vivo: BT-474 xenografted female NOD.CB17-Prkdcscid/J mice | ||||||||||||||||||||||||||||||||||
Polymeric NPs and Micelles | |||||||||||||||||||||||||||||||||||||||
[100] | ACUPA (PSMA-targeting) | O | -carborane | 150–165 nm/1.86%/- | In vivo: PC3-flu and PC3-pip prostatic adenocarcinoma cells; ex vivo, in vivo: PC3-flu and PC3-pip xenografted male athymic mice | ||||||||||||||||||||||||||||||||||
[101][102] | 1,2-bis(4-vinylbenzyl)- | closo | -carborane | 85 nm/0.26%/3.1% | In vivo: colon-26 cells; ex vivo, in vivo: colon-26 tumor-bearing BALB/c mice | ||||||||||||||||||||||||||||||||||
[103] | Decaborane | 108 nm/9.9%/60.0% | Ex vivo: female Sprague−Dawley rats and U14 tumor-bearing female KM mice | Ex vivo and in vivo on U14 tumor-bearing female KM mice: tumor growth and mouse body weight | |||||||||||||||||||||||||||||||||||
[104] | Tumor penetrating RGD peptide | BSH | 25 nm/3.81%/- | In vivo: A549 human lung cancer cells, B16−F10 mouse melanoma cells, C6 rat glioma cells, 4T1 mouse breast cancer cells and HeLa cervical cancer cells; ex vivo: A549 tumor-bearing BALB/c nude mice and B16F10 tumor-bearing mice | |||||||||||||||||||||||||||||||||||
[105] | BSH | 36 nm/-/- | In vivo: C26 mouse colorectal carcinoma and human aortic endothelial cells; ex vivo: C26 tumor-bearing BALB/c mice | Ex vivo and in vivo on C26 tumor-bearing BALB/c mice: tumor growth and mouse body weight | |||||||||||||||||||||||||||||||||||
[106][107] | O | -carborane | 100–150 nm/4.8–5.6%/- | In vivo: B16 melanoma cells; ex vivo: B16 melanoma-bearing mice | |||||||||||||||||||||||||||||||||||
[108] | BPA | 145 nm/-/> 95% | In vivo: U87MG human glioblastoma cells | In vivo on CR-39 detectors | |||||||||||||||||||||||||||||||||||
[109] | Tetraboronated porphyrin | 100 nm/-/- | In vivo: mouse melanoma B16-F10 and 4T1 mouse breast cancer cells; ex vivo, in vivo: B16-F10 tumor-bearing C57BL/6 mice and 4T1 tumor-bearing BALB/c mice | Ex vivo and in vivo on B16−F10 tumor-bearing mice | |||||||||||||||||||||||||||||||||||
[110] | Carborane | 110 nm/11.38%/- | In vivo: 4T1 mouse breast cancer cells; ex vivo, in vivo: 4T1 tumor-bearing mice | In vivo on 4T1 tumor-bearing mice | |||||||||||||||||||||||||||||||||||
[111] | Galactose | Carborane | 135 nm/3%/- | In vivo: CAL27 oral adenosquamous carcinoma, U251 glioma and HepG2 hepatocellular carcinoma cells | In vivo on HepG2 cells: apoptosis rate | ||||||||||||||||||||||||||||||||||
[112] | Carborane-containing arene ruthenium complex | 19 nm/-/- | In vivo: A2780 and A2780 cisplatin-resistant human ovarian cancer cells | In vivo on A2780 and A2780cisR cells: cell viability | |||||||||||||||||||||||||||||||||||
[113] | Dodecaborate | 13–15 nm/-/- | In vivo: U87 human glioblastoma, HeLa cervical cancer and Jurkat cells | ||||||||||||||||||||||||||||||||||||
Other NPs | |||||||||||||||||||||||||||||||||||||||
[114] | Folic acid | Boron oxide | 20–50 nm/8% mol B/NP/- | In vivo: HeLa cervical cancer cells | In vivo on HeLa cells: cell viability | ||||||||||||||||||||||||||||||||||
[115] | Folic acid | 255 nm/9.8%/- | In vivo: erythrocytes and platelets from human plasma specimens, MO7e human megakaryoblastic leukemia cells, DHD colon carcinoma cells, UMR osteosarcoma cells | ||||||||||||||||||||||||||||||||||||
[116] | 5 nm/30% of boron atoms/NP/- | In vivo: on ALTS1C1 mouse astrocytes | In vivo on cells: cell viability | ||||||||||||||||||||||||||||||||||||
[117] | Phenyl- | 10 | B-boronic acid | 53–67 nm/2%/- | In vivo: CT26 murine colon tumor cells; ex vivo, in vivo: CT26 tumor-bearing BALB/c mice | In vivo on mice: tumor growth and body weight | |||||||||||||||||||||||||||||||||
Exosomes and Biomimetic Vesicles | |||||||||||||||||||||||||||||||||||||||
[118] | Boron-containing carbon dots | 97 nm/17.90%/85.24% | In vivo: MDA-MB-231 human breast cancer, U251 glioma and HepG2 hepatocellular carcinoma cells; ex vivo, in vivo: BALB/c nude mice, U-87 glioma-bearing mice | In vivo on mice: tumor growth and body weight | |||||||||||||||||||||||||||||||||||
[119] | 146 nm/-/- | In vivo: HEK 293 human embryonic kidney and HeLa cervical cancer cells; ex vivo: female Kunming mice |