Multifunctional Nanoparticles: Cost Versus Benefit of Adding Targeting and Imaging Capabilities

Cheng, Zhiliang; Zaki, Amr; Hui, James Z.; Muzykantov, Vladimir R.; Tsourkas, Andrew

doi:10.1126/science.1226338

Cited by 1,197 publications

(928 citation statements)

References 88 publications

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“…A few of these nanoparticles also contain targeting ligands (8,9) that aid in their internalization into tumor cells. Some of the issues with the use of targeting ligands such as added cost and complexity have recently been described (10). These designed, multifunctional nanoparticles are revealing interesting behaviors in early clinical trials, e.g., they can significantly reduce side effects of the therapeutic molecules they carry, and they do not show new side effects as a result of the nanoparticle.…”

mentioning

confidence: 99%

Correlating preclinical animal studies and human clinical trials of a multifunctional, polymeric nanoparticle

Eliasof

Lazarus

Peters

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

129

119

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Nanoparticles are currently being investigated in a number of human clinical trials. As information on how nanoparticles function in humans is difficult to obtain, animal studies that can be correlative to human behavior are needed to provide guidance for human clinical trials. Here, we report correlative studies on animals and humans for CRLX101, a 20-to 30-nm-diameter, multifunctional, polymeric nanoparticle containing camptothecin (CPT). CRLX101 is currently in phase 2 clinical trials, and human data from several of the clinical investigations are compared with results from multispecies animal studies. The pharmacokinetics of polymer-conjugated CPT (indicative of the CRLX101 nanoparticles) in mice, rats, dogs, and humans reveal that the area under the curve scales linearly with milligrams of CPT per square meter for all species. Plasma concentrations of unconjugated CPT released from CRLX101 in animals and humans are consistent with each other after accounting for differences in serum albumin binding of CPT. Urinary excretion of polymer-conjugated CPT occurs primarily within the initial 24 h after dosing in animals and humans. The urinary excretion dynamics of polymer-conjugated and unconjugated CPT appear similar between animals and humans. CRLX101 accumulates into solid tumors and releases CPT over a period of several days to give inhibition of its target in animal xenograft models of cancer and in the tumors of humans. Taken in total, the evidence provided from animal models on the CRLX101 mechanism of action suggests that the behavior of CRLX101 in animals is translatable to humans.nanomedicine | clinical translation | interspecies scaling | pharmacodynamics | Nanoparticles

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mentioning

confidence: 99%

Correlating preclinical animal studies and human clinical trials of a multifunctional, polymeric nanoparticle

Eliasof

Lazarus

Peters

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

129

119

View full text Add to dashboard Cite

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“…and have succeeded in enhancing the efficacy of DDS. Some nanoparticles using active targeting strategy have proceeded to phase I/II clinical trials and have shown positive results [4]. The active targeting strategy can increase the accumulation of drugs in the desired tissue and reduce side effects.…”

Section: Benefits Of Active Targeting On Drug Delivery System (Dds)mentioning

confidence: 99%

“Programmed packaging” for gene delivery

Hyodo

Sakurai

Akita

et al. 2014

Journal of Controlled Release

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We report on the development of a Multifunctional Envelope-type Nano Device (MEND) based on our packaging concept "Programmed Packaging" to control not only intracellular trafficking but also the biodistribution of encapsulated compounds such as nucleic acids/proteins/peptides. Our strategy for achieving this is based on molecular mechanisms of cell biology such as endocytosis, vesicular trafficking, etc. In this review, we summarize the concept of programmed packaging and discuss some of our recent successful examples of using MENDs. Systematic evolution of ligands by exponential enrichment (SELEX) was applied as a new methodology for identifying a new ligand toward cell or mitochondria. The delivery of siRNA to tumors and the tumor vasculature was achieved using pH sensitive lipid (YSK05), which was newly designed and optimized under in vivo conditions. The efficient delivery of pDNA to immune cells such as dendritic cells has also been developed using the KALA ligand, which can be a breakthrough technology for DNA vaccine. Finally, ss-cleavable and pH-activated lipid-like surfactant (ssPalm) which is a lipid like material with pH-activatable and SS-cleavable properties is also introduced as a proof of our concept.

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“…Each of these functionalities could bring further complexity to the design [11]. Here, we focus on the trade-off between achieving such multifunctional "magic bullets" and specificity at the nanoscale in the effort to improve early stage detection and reduce collateral damage as side effects, central issues in the field of nanotechnology in cancer treatment.…”

Section: Introductionmentioning

confidence: 99%

The potential legacy of cancer nanotechnology: cellular selection

Patra

Turner

2014

Trends in Biotechnology

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Overexpression of oncogenes or loss of tumour suppressors can transform a normal cell to a cancerous one, resulting in uncontrolled regulation of intracellular signaling pathways and immunity to stresses, which both pose therapeutic challenges.Conventional approaches to cancer therapy, although they are effective at killing cancer cells, may still fail due to inadequate biodistribution and unwanted side effects.Nanotechnology-based approaches provide a promising alternative, with the possibility of targeting cells at an early stage, during their transformation into cancer cells. This review considers techniques that specifically target those molecular changes, which begin in only a very small percentage of normal cells as they undergo transformation. These techniques are crucial for 'early-stage' diagnosis and therapy.3

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Multifunctional Nanoparticles: Cost Versus Benefit of Adding Targeting and Imaging Capabilities

Cited by 1,197 publications

References 88 publications

Correlating preclinical animal studies and human clinical trials of a multifunctional, polymeric nanoparticle

Correlating preclinical animal studies and human clinical trials of a multifunctional, polymeric nanoparticle

“Programmed packaging” for gene delivery

The potential legacy of cancer nanotechnology: cellular selection

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