Table of tumor growth (Vachutinsky et al.,

Table 2. RGD modified Drugs

Carrier system

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Drug

Conjugation

Tumor model

Liposomes

Combretastatin A-4 (CA-4) and Dox

RGD-CA-4 and Dox
 

B16 and B16F10 melanoma cells (Zhang et al., 2010)

Dendrimers

Dox

RGD-PEG-PAMAM-DOX

C6 glioma cells (Zhang et al., 2011)

Nanoparticles

Paclitaxel

PTX-RGD/Tf-NPs

HeLa cells (Xu et al., 2012a)

Liposomes

Docetaxel

RGD-PEG-LP-DC

BT-20 and MDA-MB-231 cells (Naik et al., 2012)

Albumin nanoparticles

Gemcitabine

RGD-NPs

BxPC3 Pancreatic cancer cells (Xu et al., 2012b)

HPMA conjugates

Gelganamycine

c(RGDfk)

DU-145 (Borgman et al., 2009)

Micelles

Paclitaxel

c(RGDfk)-Ptx

U87MG glioblastoma (Zhan et al., 2010)

 

 Table 3. RGD modified Proteins and Peptides

Protein/ Peptides

Conjugation

Tumor model

Osteopontin

RGD-containing Osteopontin

Avian osteoclast-like cells (Tanabe et al., 2011)

Fibulin-5

RGD-fibulin-5

A549, H1299 and H460 cells (Yue et al., 2009)

The angiogenic 
factor Del1

RGD-Mediated
angiogenic factor 

Human umbilical vein endothelial
cells (Tugulu et al., 2007)

tTf

(RGD)3/tTF

H460 lung cancer cells (Yan et al., 2007)

IL-2

RGD4C

NXS2 Neuroblastoma (Dickerson et al., 2004)

TNF-?

RGD4C

RMA lymphoma cells (Curnis et al., 200)

Endostatin

RGD-peptide

MGC-803 gastric cancer cells (Xu et al., 2008)

 

4.3.3.2. RGD-Modified Gene Carriers for Treatment of Tumor         

RGD-modified non-viral and viral carries have been developed for the effective and safe gene delivery.

RGDs may be modified by covalent interaction of the RGD-peptide to the different types of lipids, peptides and cationic polymers etc. These modified RGD may be used to the delivery of short interfering RNA (siRNA) and plasmid DNA. These modified carriers have been used as non-viral gene carriers. Non-viral gene carriers with their uses and experimental models are discussed in table 4.

Vachutinsky et al., 2011, prepared polyplex micelles ion complexation of the polymers (c(RGDfK)-PEG-P(Lys-SH)) with sFlt-1 plasmid DNA which shows inhibition of tumor growth  (Vachutinsky et al., 2011). These micelles concentrated on the tumor site and interacted with tumor endothelialcells via receptor-mediated endocytosis as shown in figure 3.

Table 4. RGD-modified non-viral carries for gene delivery (Temming et al., 2005).

Carrier

Gene

Conjugation

Tumor Model

Liposomes
 

siRNA

RGD-PEGylated liposomes

Pigment epithelial cells (Kibria et al., 2011)

RGD-Lipo-
siRNA (MDR1)

RGD-SSL-DOX liposomes

Breast cancer MCF7/A cells (Jiang et al., 2010)

Lipid

ATP-Raf

Polymerized lipid nanoparticle

M21-L/CT26 colon carcinoma (Hood et al., 2002)

Peptides

siLacZ, siLuciferase

RGD-HK-branched peptides

MDA-MB-435c,MCF7 (Leng and Mixson, 2005)

Anti-cancer p53 gene

RGDGWK-lipopeptde

B16F10 tumor (Samanta et al., 2010)

Polymer
 

PEG-PEI/DNA complexes

RGD-PEG

NIH3T3 cells (Orsi et al., 2012)

Plasmid DNA

RGD-PEG-PEI

Intracranial glioblastoma (Zhan et al., 2012)

siRNA

RGD-PEG-PCL

B16F10-luc2 lung metastatic (Yonenaga et al., 2012)

Plasmid DNA coding luciferase

RGD-PEG-Suc

Melanoma cell (Sakae et al., 2008)

Table 2. RGD modified Drugs

Carrier system

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Drug

Conjugation

Tumor model

Liposomes

Combretastatin A-4 (CA-4) and Dox

RGD-CA-4 and Dox
 

B16 and B16F10 melanoma cells (Zhang et al., 2010)

Dendrimers

Dox

RGD-PEG-PAMAM-DOX

C6 glioma cells (Zhang et al., 2011)

Nanoparticles

Paclitaxel

PTX-RGD/Tf-NPs

HeLa cells (Xu et al., 2012a)

Liposomes

Docetaxel

RGD-PEG-LP-DC

BT-20 and MDA-MB-231 cells (Naik et al., 2012)

Albumin nanoparticles

Gemcitabine

RGD-NPs

BxPC3 Pancreatic cancer cells (Xu et al., 2012b)

HPMA conjugates

Gelganamycine

c(RGDfk)

DU-145 (Borgman et al., 2009)

Micelles

Paclitaxel

c(RGDfk)-Ptx

U87MG glioblastoma (Zhan et al., 2010)

 

 Table 3. RGD modified Proteins and Peptides

Protein/ Peptides

Conjugation

Tumor model

Osteopontin

RGD-containing Osteopontin

Avian osteoclast-like cells (Tanabe et al., 2011)

Fibulin-5

RGD-fibulin-5

A549, H1299 and H460 cells (Yue et al., 2009)

The angiogenic 
factor Del1

RGD-Mediated
angiogenic factor 

Human umbilical vein endothelial
cells (Tugulu et al., 2007)

tTf

(RGD)3/tTF

H460 lung cancer cells (Yan et al., 2007)

IL-2

RGD4C

NXS2 Neuroblastoma (Dickerson et al., 2004)

TNF-?

RGD4C

RMA lymphoma cells (Curnis et al., 200)

Endostatin

RGD-peptide

MGC-803 gastric cancer cells (Xu et al., 2008)

 

4.3.3.2. RGD-Modified Gene Carriers for Treatment of Tumor         

RGD-modified non-viral and viral carries have been developed for the effective and safe gene delivery.

RGDs may be modified by covalent interaction of the RGD-peptide to the different types of lipids, peptides and cationic polymers etc. These modified RGD may be used to the delivery of short interfering RNA (siRNA) and plasmid DNA. These modified carriers have been used as non-viral gene carriers. Non-viral gene carriers with their uses and experimental models are discussed in table 4.

Vachutinsky et al., 2011, prepared polyplex micelles ion complexation of the polymers (c(RGDfK)-PEG-P(Lys-SH)) with sFlt-1 plasmid DNA which shows inhibition of tumor growth  (Vachutinsky et al., 2011). These micelles concentrated on the tumor site and interacted with tumor endothelialcells via receptor-mediated endocytosis as shown in figure 3.

Table 4. RGD-modified non-viral carries for gene delivery (Temming et al., 2005).

Carrier

Gene

Conjugation

Tumor Model

Liposomes
 

siRNA

RGD-PEGylated liposomes

Pigment epithelial cells (Kibria et al., 2011)

RGD-Lipo-
siRNA (MDR1)

RGD-SSL-DOX liposomes

Breast cancer MCF7/A cells (Jiang et al., 2010)

Lipid

ATP-Raf

Polymerized lipid nanoparticle

M21-L/CT26 colon carcinoma (Hood et al., 2002)

Peptides

siLacZ, siLuciferase

RGD-HK-branched peptides

MDA-MB-435c,MCF7 (Leng and Mixson, 2005)

Anti-cancer p53 gene

RGDGWK-lipopeptde

B16F10 tumor (Samanta et al., 2010)

Polymer
 

PEG-PEI/DNA complexes

RGD-PEG

NIH3T3 cells (Orsi et al., 2012)

Plasmid DNA

RGD-PEG-PEI

Intracranial glioblastoma (Zhan et al., 2012)

siRNA

RGD-PEG-PCL

B16F10-luc2 lung metastatic (Yonenaga et al., 2012)

Plasmid DNA coding luciferase

RGD-PEG-Suc

Melanoma cell (Sakae et al., 2008)

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