Table 2.

Summary of nanobrachytherapy-based preclinical studies.

Main type of emission	Nanoparticle	Study (tumor model) type	Target	Main results	Reference
α	AuNPs (5 and 15 nm) functionalized with a peptide from Substance P(5-11) and labeled with 211At.	In vitro (-).	NK1 receptors overexpressed in T98G glioma cells.	The authors recommended the intratumoral injection of the NPs instead of intravenous injection due to the their large size.	(51)
α	AuNPs (5 nm) with chemically adsorbed 211At and activated with PEG and trastuzumab.	In vitro (-).	HER-2 proteins overexpressed in SKOV-3 cell ovarian cancer cells.	AuNP-S-PEG-trastuzumab bioconjugate was effectively internalized by SKOV-3 cells and reduced the metabolic activity of ovarian cancer cells with a median lethal dose of 0.5 MBq/mL.	(57)
α	AuNPs (5–9 nm) radiolabeled with 225Ac using TADOTAGA chelator.	In vivo (U-87 MG tumor xenograft).	Nanobrachytherapy for xenograft bearing U-87 MG human glioblastoma–astrocytoma cells.	For mice (therapy group) injected with 100 μL/5 kBq of [225Ac]225Ac-Au@TADOTAGA per mouse (on days 1, 3, and 5), the tumor volume was reported to be ≈2.4 times lower after 8 days of radioactive injection and ≈4 times lower after 22 days of injection, in comparison with the control group.	(14)
Auger electrons	AuNPs coated with a layer of 103Pd (120 nm).	In vivo (PC-3 tumor xenograft).	Nanobrachytherapy for prostate cancer.	After 5 weeks of radioactive injection (1.5 mCi per mouse), the decrease in tumor volume by about 75% for the 103Pd@Au-treated group was reported, and over 95% of NPs still remained in the tumor.	(72)
Auger electrons	AuNPs radiolabeled with 111ln (30 nm) using DTPA chelator and functionalized with PEG and trastuzumab.	In vivo (subcutaneous HER2-overexpressing breast cancer (BC) xenografts).	HER-2-positive BC cells.	Therapeutic effectiveness of trastuzumab-AuNP-111ln was assessed by intratumorally injecting 10 MBq of radiopharmaceutical to the BC murine model. Inhibition in growth of tumor was reported for the treated group, whereas in the case of an untreated group, the tumors grew to eightfold of the initial tumor size.	(52)
Auger electrons	103Pd core coated with Au or 198Au (5–30 nm) functionalized with PEG.	In vivo (PC-3 tumor xenograft).	PC-3 prostate cancer cells.	4 weeks post radioactive injection (single dose of 1.6–1.7 mCi per mouse), a delay in tumor growth by 56% and 75% was reported for 103Pd@AuNPs and 103Pd@198AuNPs, respectively, with respect to the controls. 75% of the injected dose was detected in the tumor.	(15)
Auger electrons	Covalent organic frameworks (COF)-Ag particles conjugated with PEG and radiolabeled with 125I.	In vivo (PC-3 tumor xenograft).	PC-3 prostate cancer cells.	For the 125I-COF-treated group (injected with 1 mCi of PEG-COF-Ag-125I per mouse), reduction in tumor volume by about 63% in comparison with the initial size was reported.	(45)
Auger electrons	Nanogel with 103Pd-AuNPs coated with poly(N-isopropylacrylamide) (37.3 nm).	In vivo (CT26 colorectal tumor xenograft).	CT26 colorectal cancers.	The delay in the tumor growth for treated group (injected with 25 MBq of radioactive LOIB : EtOH-[103Pd]AuPd nanogel) after day 10 p.i. was reported in comparison with the control and cold nanogel groups. Further, the ex vivo biodistribution studies elucidated that up to 95%ID/g of injected radioactive nanogel was retained in the tumor post day 20 of injection.	(38)
β	198Au-poly(amidoamine) dendrimer nanoparticles (10–50 nm)	In vivo (B16F10 melanoma tumor model).	B16F10 tumor cells.	Reduction in tumor growth by more than 45% was observed for Group B mice (injected with 74 μ of poly{198Au}) in comparison with the control and Group A mice (injected with 35 μCi of poly{198Au}).	(11)
β	198AuNPs stabilized with gum arabic (4–10 nm).	In vitro (PC-3 tumor cell lines) and in vivo (PC-3 tumor xenograft)	PC-3 prostate cancer cells.	In vitro stability studies demonstrated excellent stability of GA-198AuNPs for periods of over 6 months. The biodistribution studies performed in a murine model demonstrated that more than 85% of GA-198AuNPs were contained in the liver.	(73)
β	198AuNPs stabilized with gum arabic (12–18 nm).	In vivo (PC-3 tumor xenograft).	PC-3 prostate cancer cells.	After 3 weeks of radioactive injection (408 μCi of GA-198AuNP per mouse), the tumor volumes of treated groups were found to be 82% smaller than those of the control group. Furthermore, even after 30 days of injection, on ex vivo analysis, radioactive nanoparticles were found in the tumor (20% ID), the liver (1% ID), and the carcass (18.5% ID).	(35)
β	198Au-EGCg nanoparticles	In vivo (PC-3 tumor xenograft).	Lam 67R receptors in prostate cancer cells.	After 24 h of radioactive injection (136 μCi of 198Au-EGCg nanoparticles per mouse), approximately 72% of nanoparticles were retained in the tumor. After 28 days of injection, the tumor size of the treated group was found to be 80% smaller than that of the control group.	(36)
β	198AuNPs stabilized with gum arabic (12–15 nm).	In vivo (dogs diagnosed with prostate cancer).	Spontaneous prostate cancer in dogs.	The dogs were injected with activity in the range of 3 to 13.8 mCi of 198Au. A decrease in tumor volume by 30%–50% was observed in two specimens; an increase in tumor size by 12%–26% was observed in 2 dogs; and for the remaining specimens, there was an increase or decrease of 3% in tumor volume (probably due to limited retention in the tumor volume).	(74)
β	Mangiferin-198Au nanoparticles (35 nm)	In vivo (PC-3 tumor xenograft).	PC-3 prostate cancer cells.	Mice bearing prostate cancer were divided into three groups: Group A and Group B were injected with 160 μCi/30 μL of MGF-198AuNPs, and Group C was injected with 30 μL of saline. After 2 weeks of injection, a decrease in tumor volume by 2 fold with respect to control was reported for the treated groups. Three weeks post radioactive injection, there was an increase in tumor volume by fivefold for Group C; Group A = 0.18 ± 0.17 cm3 and Group B = 0.22 ± 0.02 cm3 were reported. Furthermore, after 3 weeks, 69.70 ± 14.40%ID was found to be retained in the tumor, 6.80 ± 5.9%ID in the carcass, and 1.44 ± 2.97%ID in the liver.	(10)
β	198AuNPs stabilized with gum arabic (~2 nm).	In vivo (H460 tumor xenograft).	H460 non-small cell lung cancer cells.	Post 7 days of injection (103 μCi of 198AuNPs@GA per mouse), a decrease in tumor volume by more than 90% was observed in the 198AuNPs@GA-treated group in comparison with the controls and mice injected with non-radioactive nanoparticles. Even after 2 weeks of radioactive injection, 50% of the nanoparticles were found to be accumulated in the tumor and 8.9% in the liver.	(49)
β	AuNPs radiolabeled with 177Lu via DOTA chelator, functionalized with PEG and panitumumab.	In vivo (MDA-MB-468 human breast cancer mice model)	MDA-MB-468 human breast cancer cells.	A single dose of 4.5 MBq of 177Lu-AuNP was intratumorally administered to the mice carrying subcutaneous BC cells. No significant impact of active targeting of 177Lu-AuNP was observed in retaining the AuNPs within the tumors. Less than 3%ID/g radioactivity migrated to the liver and spleen, and its value increased by two to fivefold post 48 h of injection, whereas the radioactivity found in other organs was less than 0.5%ID/g. In the treated groups, inhibition of tumor growth by a factor of ≈30 in comparison with the untreated groups was reported.	(50)
β	AuNPs radiolabeled with 177Lu via DOTA chelator, functionalized with PEG and trastuzumab (30 nm).	In vivo (breast cancer xenografts).	BC tumor cells.	3 MBq of 177LuAuNPs was injected intratumorally to each mouse. The targeted nanoparticles (trastuzumab-AuNP-177Lu) were reported to be 1.8 times more efficient in inhibiting tumor growth in comparison with the non-targeted (AuNP-177Lu) and 2.2 times in comparison with the untreated group.	(75)
β	199AuNPs stabilized with [f(RGDfK)] peptide (11 nm).	In vivo (melanoma tumor xenograft).	Integrin αvβ3 receptors in melanoma cells.	Significant delay in tumor growth was observed in mice injected with 2, 5, or 10 MBq of 199Au-c(RGDfK) nanoparticles in comparison with the control.	(37)
β	Melanin-silver nanoparticles radiolabeled with 131I cyan (6 nm).	In vivo (PC-3 tumor xenograft).	PC-3 prostate cancer cells.	The MNP-Ag-131I-treated group (injected with 500 mCi of 131I) had tumor volume equal to initial volume, whereas the control and 131I-treated group had tumor size 1.5 times larger in comparison with the initial volume.	(17)
β	Mesoporous silica nanoparticles radiolabeled with 131I and activated with anti-VEGFR2 antibodies and bovine serum albumin.	In vivo (thyroid cancer-bearing mice).	VEGFR2 in human thyroid carcinoma FRO cells.	The mice were intratumorally administered with a single dose of 74 MBq of radioactive nanoparticles. Gradual increase in tumor volume was reported for all the groups except 131I-BSA-MSNPs-anti-VEGFR2-treated group.	(76)
β	AuNPs radiolabeled with 131I and activated with twin arginine translocation (TAT) peptide (~8.36 nm).	In vivo (HCT-116 colon cancer xenografts).	Human colon cancer (HCT-116) cells in vivo.	After 18 days of radioactive injection (500 μCi/mL per mouse), reduction in tumor size by 79.95% was reported for the 131I-AuNPs-TAT-treated group, whereas in the untreated group, the tumor grew to 8.08 times the original tumor size.	(77)