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Table 1 Radiosensitizing effect of high-Z metal NPs in glioblastoma model

From: Radiosensitizing high-Z metal nanoparticles for enhanced radiotherapy of glioblastoma multiforme

High-Z metal

Particle name (commercial or by the authors)

Coating

Hydrodynamic Size

Functionalization

Injection mode

Concentration of NPs administerated in vivo

Concentration of NPs in tumor

Radiation source

In vitro/In vivo

Radiation Energy

Radiation dose

Cells and tumor models

Radiosensitizing effect

Refs

Gold

GNPs

PEG

23 nm

None

i.v.

1.25 g Au/kg

3.7% ID/g

Tissue of gold

Small Animal Radiation Research Platform

In vitro

150 kVp

0 ~ 6 Gy

U251

SER = 1.3

Johet al. [88]

In vivo

175 kVp

20 Gy

U251 orthotopic mouse model

Median survival time: RT vs. NP + RT: 14 vs. 28 days

AuNPs-Pt

PEI

50 nm

Cisplatin

In vitro only

In vitro only

In vitro only

Cesium-137 beam radiator

In vitro

1 Gy per minute

10 Gy

S1, S2, SP56 (Patient-derived GBM cell line)

NP + RT: Complete cancer ablation

RT: Recurrence

Setua et al. [90]

BSA-AuNPs

BSA

28 nm

None

i.v.

1.3 mg/mL BSA-AuNPs

2%ID/g

Tissue of gold

N.R.

In vitro

160 kVp X-ray

0 ~ 8 Gy

U87

SER = 1.37

Chen et al. [89]

In vivo

160 kVp

5 Gy

U87 subcutaneous mouse model

Tumor weight: RT vs. NP + RT = 0.15 g vs. 0.1 g

pAuNTs (Au nanotriangles)

None

61.51 nm (Narrow edge length)

PEG

i.v.

2.7 mg/kg pAuNTs

5000 ng/g (Au/tissue)

XRAD 320 orthovoltage irradiator

In vitro

250 kVp X-rays

0 ~ 6 Gy

MCF-7, U87MG

Maximum reduction of surviving fraction: 3-4 Gy

Bhattarai et al. [9]

In vivo

N.R

U87MG subcutaneous mouse model

DEF = 2.67

Time to tripling of tumor: RT vs. NP + RT = 3 days vs. 8 days

Gadolinium

GdBN

Polysiloxane shell

3 nm

None

In vitro only

In vitro only

In vitro only

Gamma radiation, Cobalt source (60Co) at CEA

In vitro

1.25 MeV (1 Gy per minute)

0–7 Gy

U87

Enhancing factor2 Gy = ~ 23%

Stefancikov et al. [105]

GdBNs

Polysiloxane shell

3 nm

None

In vitro only

In vitro only

In vitro only

Gamma ray, 60Co irradiator

In vitro

1 Gy per minute

0–4 Gy

U87

Survival fraction: RT vs. NP + RT = 0.81 vs. 0.55 (1 Gy)

RT vs. NP + RT = 0.42 vs. 0.37 (4 Gy)

Stefancikova et al. [70]

Gd-based particle

Polysiloxane shell

3 nm

None

In vitro only

In vitro only

In vitro only

137Cs source irradiator, Pantak Therapax STX 150 apparatus

In vitro

660 keV

0–8 Gy

U87

DNA DSBs of GdNP + 5 Gy: 84% versus RT only

Cell killed by NP sensitizing effect (2 vs. 5 vs. 8 Gy: 12.5% vs. 25% vs. 37%)

Le Duc et al. [103]

Silver

AgNPs

Citrate

26.75 nm

None

i.t.

10 μg (mass-AgNPs) 5.48 μg (mol-AgNPs)

N.R

linear accelerator

In vitro

6 MV X-rays (200 cGy per minute)

0–8 Gy,

U251

SER: mas-AgNPs: 1.64  mol-AgNPs: 1.44

Liu et al. [115]

vertical accelerator

In vivo

6 MV X-rays

8 Gy

U251 orthotopic

mouse model

MST: RT vs. mas-AgNP + RT vs. mol-AgNP + RT = 35 days vs. 62 days vs. 51 days)

AgNPs

PVP

88.6 nm

None

i.t.

10 μg or 20 μg

N.R

Vertical beam with linear accelerator

In vivo

6 MV X-rays (200 MU per minute)

10 Gy

C6 orthotopic rat model

MST: IR vs. 10 μg AgNPs + RT vs. 20 μg AgNPs + RT = 24.5 vs. 33.5 vs. 37.0 days

Liu et al. [114]

Iron oxide

Iron oxide

cetuximab-IONPs

Amphiphilic polymer

Core size: 10 nm

Cetuximab

CED

0.3 mg/mL

N.R

X-RAD

In vitro

320 kV, 10 mA (1.2 Gy per minute)

10 Gy

U87MGEGFRvIII

Cetuximab-IONP + RT: higher density of DNA DSBs, enhanced intracellular ROS production

Bouras et al. [37]

In vivo

320 kV, 10 mA (1.2 Gy per minute)

10 Gy x 2 (24, 72 h)

U87MGEGFRvIII orthotopic mouse model

MST: RT vs. cetuximab-IONPs + RT = 15 vs. 60

SPION-cmHsp70.1

Dextran

54.8 nm

Monoclonal cmHsp70.1 antibody

i.v.

2.5 mg/kg

N.R

N.R

In vitro

N.R

0–20 Gy

C6, K562, HeLa

Dramatical increase in surface density of Hsp 70 by radiotherapy

Shevtsov et al. [122]

Monochromatic X-ray beams, SARRP irradiator,

In vivo

225 kVp

10 Gy

C6 orthotopic rat model

SPION-cmHsp70.1 uptake was enhanced by radiotherapy

Bismuth oxide

Bi2O3 NP

None

50–70 nm

None

In vitro only

In vitro only

In vitro only

Nucletron Oldelft Therapax, Elekta Axesse™ LINAC

In vitro

125 kVp,

10 MV

0–8 Gy,

9L

SER (125kVp) = 1.48

SER (10 MV) = 1.25

Stewart et al. [123]

TIONTs

TiONts

None

10 nm

None

In vitro only

In vitro only

In vitro only

linear photon accelerator (clinic600, Varian)

In vitro

N.R

0–10 Gy

SNB-19, U87MG

SF2 Gy (SNB19): RT vs. NP + RT = 0.36 vs. 0.18

SF2 Gy (U87MG): RT vs. NP + RT = 0.60 vs. 0.43

Mirjolet [124]

Tantalum pentoxide

Tantalum pentoxide

NSPs

None

56 nm

None

In vitro only

In vitro only

In vitro only

Clinical LINAC

In vitro

10 MV X-rays

0–8 Gy

9L

SER = 1.33

Brown et al. [113]

Gold, Iron oxide

GSMs

PEG-PCL copolymer

~ 100 nm

None

i.v.

300 mg Au/kg

Brain tumor: 1.7% ID/g, flank tumor: 2.2% ID/g

Small Animal Radiation Research Platform (SARRP)

In vitro

150 kVp, 0.5 mA

4 Gy

U251, U373

DNA DSBs change (U251) = 1.8-fold

DNA DSBs change (U373) = 2.4-fold

Sun et al. [127]

N.R

In vivo

N.R

N.R

U251 orthotopic mouse model

GSM uptake (Normal brain:brain tumor = 1:97)

BaYbF5:2% Er3+

UCA-RGD

None

22 nm

RGD peptide

i.v.

70 mg Yb/kg (7 mg Yb/mL)

7.5% ID Yb/g

Siemens Primus clinical linear accelerator

In vitro

6 MeV

8 Gy

U87MG

Cell uptake is enhanced by RGD peptide

Xing et al. [126]

In vivo

6 MeV

8 Gy

U87MG

Subcutaneous

mouse model

Tumor volume shrinkage of UCA-RGD + RT group = 35%

  1. PEG: polyethylene glycol; PEI: polyethylenimine; PVP: polyvinylpyrrolidone; cmHsp70.1: Hsp70.1-specific antibody; PEG-PCL: polyethylene glycol-polycaprolactone; i.v: intravenous injection; i.t: intratumoral injection; CED: convection-enhanced delivery; RT: radiation therapy; IR: Ionizing radiation; SER: sensitizer enhancement ratio; DEF: dose enhancement factor; DSBs: double-stranded breaks; MST: Median survival time; SF: Survival fraction; ROS: reactive oxygen species