Tumor angiogenic vasculature targeting with PAMAM dendrimer–RGD conjugates

Shukla, R. C.; Thomas, Thommey P.; Peters, Jennifer L.; Kotlyar, Alina; Myc, Andrzej; Baker, James R.

doi:10.1039/b507350b

Cited by 198 publications

(174 citation statements)

References 16 publications

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“…The identification of molecular markers that differentiate newly formed capillaries from their mature counterparts has paved the way for targeted delivery of cytotoxic agents to the tumor vasculature (19). The RGD sequence of some adhesion molecules is recognized by several cell surface integrins (20). In our study, the RGD peptide used for the construction of the RGD-FasL fusion protein has a conformationally restrained RGD sequence that binds toV3 with specificity and high Blood samples were collected retro-orbitally from all the treated groups to detect the levels of serum alanine transaminase (ALT) and aspartate aminotransferase (AST).…”

Section: Discussionmentioning

confidence: 99%

RGD-FasL Induces Apoptosis in Hepatocellular Carcinoma

et al. 2009

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Section: Discussionmentioning

confidence: 99%

RGD-FasL Induces Apoptosis in Hepatocellular Carcinoma

et al. 2009

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“…An early example of in vivo passive targeting Is the conjugation of a sodium carboxyl-terminated G-3.5 polyamidoamine (PAMAM) dendrimer with cisplatin for the treatment of B16F10 induced melanomas, achieving an enhanced antitumor efficacy compared with the free drug [372]. Also, there are preclinical promising in vitro and in vivo results with active targeting dendrimers [73,365], for example antibody-dendrimer conjugates showed better efficacy than free antibodies [380][381][382][383], peptide (RGD) dendrimer conjugates showed enhanced tumor targeting [384][385][386], and folic acid functionalized dendrimers generated better tumor accumulations than untargeted controls or free drug, producing a stronger reduction of the tumor size [73,[387][388][389][390]. The slow translation of these preclinical studies to clinical trials may be due to the current toxicity of dendrimers [391,392], with the aim of the current research in the development of new biocompatible and less toxic alternatives [367,[393][394][395][396][397][398][399].…”

Section: Polymeric Nanocarriersmentioning

confidence: 99%

Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy

Pérez-Herrero

Fernández‐Medarde

2015

European Journal of Pharmaceutics and Biopharmaceutics

1,399

754

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Cancer is the second worldwide cause of death, exceeded only by cardiovascular diseases. It is characterized by uncontrolled cell proliferation and an absence of cell death that, except for hematological cancers, generates an abnormal cell mass or tumor. This primary tumor grows thanks to new vasculatization and, in time, adquires metastatic potential and spreads to other body sites, which causes metastasis and finally death. Cancer is caused by damage or mutations in the genetic material of the cells due to environmental or inherited factors. While surgery and radiotherapy are the primary treatment used for local and non-metastatic cancers, anti-cancer drugs (chemotherapy, hormone and biological therapies) are the choice currently used in metastasic cancers. Chemotherapy is based on the inhibition of the division of rapidly growing cells, which is a characteristic of the cancerous cells, but unfortunately, it also affects normal cells with fast proliferation rates, like the hair follicles, bone marrow and gastrointestinal tract cells, generating the characteristic side effects of chemotherapy. The indiscriminate destruction of normal cells, the toxicity of conventional chemotherapeutic Código de campo cambiado

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“…Many strategies have been employed for these purposes, including PEGylation to prolong circulation time in the bloodstream, 6 acetylation to reduce toxicity, 7 conjugation of specific ligands to selectively target tumor cells, 8 and grafting functional peptides or amino acids to enhance transfection efficacy. 9,10 Some hydrophobic moieties have been adopted to enhance the transfection ability of cationic gene delivery carriers.…”

Section: Introductionmentioning

confidence: 99%

Sequential Conjugation of 6-Aminohexanoic Acids and L-Arginines to Poly(amidoamine) Dendrimer to Modify Hydrophobicity and Flexibility of the Polymeric Gene Carrier

Yu¹,

Yu²,

Choe³

et al. 2011

Bulletin of the Korean Chemical Society

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We synthesized a novel cationic dendrimer consisting of a poly(amidoamine) dendrimer (PAMAM, generation 4) backbone with both L-arginine (Arg) at the termini and 6-aminohexanoic acid (Ahx) between the original core polymer and the peripheral Arg units. The sequential chemical modification of PAMAM G4 with Ahx and Arg resulted in higher transfection efficiency with much less cytotoxicity. PAMAM G4-Ahx-Arg formed stable polyplexes at weight ratios of 8:1 or higher (polymer: plasmid DNA), and the mean polyplex diameter was 180 ± 20 nm. PAMAM G4-AhxArg showed much higher transfection ability than PAMAM G4 or PAMAM G4-Ahx. Furthermore, PAMAM G4-Ahx-Arg was much less cytotoxic than PEI25KD and PAMAM G4-Arg. In addition to Arg grafting of the PAMAM dendrimer, which endows a higher transfection capability, the addition of Ahx spacer increased dendrimer hydrophobicity, introduced flexibility into the conjugated amino acids, and reduced cytotoxicity. Overall, it appears that the concomitant modification of PAMAM with Ahx and Arg could lead to new PAMAM conjugates with better performances.

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Tumor angiogenic vasculature targeting with PAMAM dendrimer–RGD conjugates

Abstract: PAMAM dendrimer-RGD-4C peptide conjugate was synthesized and in vitro targeting efficacy to integrin receptor expressing cells was studied by flow cytometry and confocal microscopy.

Cited by 198 publications

References 16 publications

RGD-FasL Induces Apoptosis in Hepatocellular Carcinoma

RGD-FasL Induces Apoptosis in Hepatocellular Carcinoma

Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy

Sequential Conjugation of 6-Aminohexanoic Acids and L-Arginines to Poly(amidoamine) Dendrimer to Modify Hydrophobicity and Flexibility of the Polymeric Gene Carrier

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