The Role of the Size and Number of Polyethylene Glycol Chains in the Biodistribution and Tumor Localization of Triazine Dendrimers

Lim, Jongdoo; Guo, Yi; Rostollan, Cynthia L.; Stanfield, Jennifer; Hsieh, Jer Tsong; Sun, Xiankai; Simanek, Eric E.

doi:10.1021/mp8000292

Cited by 76 publications

(57 citation statements)

References 37 publications

(36 reference statements)

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“…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

1,326

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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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

1,326

754

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“…More interestingly, PEGylated bow-tie G3 dendrimers with a total MW~160 kDa (t 1/2 =50 h) had a significantly lower half-life compared with PEGylated lysine dendrimers with a total MW of 68 kDa (t 1/2 =75 h), suggesting that the potentially higher clearance was due to the greater flexibility of the bow-tie polyester dendrimers (38,116). Recently, Lim et al directly compared the PEG effect in symmetrical PEG-modified polytriazine dendrimers to asymmetrical PEG-modified bow-tie polyester dendrimers (120). Based on the total MW and flexibility assumption, asymmetrically PEG-modified bow-tie dendrimers seem to require a longer PEG of 10-20 kDa (MW 85-160 kDa) to obtain a similar half-life of 40-50 h as symmetrically PEG-modified dendrimers with a shorter PEG of 2 kDa (MW 30-70 kDa).…”

Section: Pegylationmentioning

confidence: 99%

“…The numbers inserted in symbols indicate the molecular mass of the PEG chains. (Adapted from (106,114,116,118,120)). …”

Section: Targeting Ligandmentioning

confidence: 99%

Designing Dendrimers for Drug Delivery and Imaging: Pharmacokinetic Considerations

2010

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Dendrimers have well-organized high branches with a layered architecture providing a series of versatile chemical modification for various purposes. Consequently, this dendrimer nanotechnology explores a new promising class of nanoscale carriers for therapeutic drugs and imaging reagents using passive and active targeting approaches. By controlling dendritic structures, the biological fate of dendrimer/dendrimer-based drugs can be significantly altered based on their intrinsic physicochemical properties, including the hydrophilicity of the unit molecules, particle size, surface charge, and modification. Accordingly, pharmacokinetic aspects play an important role in the design and development of dendrimer systems for successful in vivo application and clinical translation. This review focuses on the recent progress regarding dendritic architectures, structure-related toxicity, and critical factors affecting the pharmacokinetics and biodistribution of dendrimer/dendrimer-based drugs. A better understanding of the basic aspects of dendritic systems and their pharmacokinetics will help to develop a rationale for the design of dendrimers for the controlled delivery of drugs and imaging reagents for therapeutic or diagnostic purposes.

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“…Others could decrease the number of toxic amyloid oligomers [55,56]. The slow translation of preclinical studies to clinical trials may be due to the toxicity of dendrimers [46,47], with the aim of the current research in the development of new biocompatible and less toxic alternatives [57,58].…”

Section: Dendrimers As Drug Delivery Systemsmentioning

confidence: 99%

Dendrimers as Drug Nanocarriers: The Future of Gene Therapy and Targeted Therapies in Cancer

Franiak-Pietryga¹,

Ziemba²,

Messmer³

et al. 2018

Dendrimers - Fundamentals and Applications

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Synthetic polymers, such as dendrimers, play a critical role in pharmaceutical discovery and development. Advances in the application of nanotechnology in medicine have given rise to multifunctional "smart" nanocarriers that can deliver one or more therapeutic agents safely and selectively to cancer cells, including intracellular gene-specific targeting. Dendrimers with their 3D nanopolymeric architectures are highly attractive class of drug and gene delivery vector. Advances in understanding and manipulating genes gave scientists a tool to make changes in people DNA to prevent or treat diseases. Over the past decade, gene therapy has been in use in clinical trials. The inactivation of the tumor suppressor genes is the main idea of the development of gene therapy in the cancer treatment. Broad spectrum of delivery concepts, including viral vectors, liposomes, cationic polymers and dendrimers, cell-penetrating peptides and gold and magnetic nanoparticles have been investigated. A well-designed vector is the most desirable approach to increase the safety of gene therapy, which is still in its infancy stages in cancer research. More experimental and clinical trials are focused on well-designed and effective doses of vectors that are essential for therapeutic efficacy of gene therapy for its potential in clinical use against a wide variety of cancers.

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The Role of the Size and Number of Polyethylene Glycol Chains in the Biodistribution and Tumor Localization of Triazine Dendrimers

Cited by 76 publications

References 37 publications

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

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

Designing Dendrimers for Drug Delivery and Imaging: Pharmacokinetic Considerations

Dendrimers as Drug Nanocarriers: The Future of Gene Therapy and Targeted Therapies in Cancer

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