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Related Concept Videos

Site-Targeted Drug Delivery Systems: Polymeric Carriers01:24

Site-Targeted Drug Delivery Systems: Polymeric Carriers

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Polymeric carriers enhance targeted drug delivery by increasing efficacy while minimizing off-target effects. These carriers comprise a biodegradable polymeric backbone integrated with functional elements that enable targeting, improve physicochemical properties, and regulate drug release.Targeting MechanismsThe targeting ability of polymeric carriers is mediated by a homing device, which is a molecular recognition component designed to selectively bind to specific tissues or cells. Monoclonal...
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RNA Interference01:23

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RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
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RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
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Porous Silicon Microparticles for Delivery of siRNA Therapeutics
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Hypoxia-Responsive Copolymer for siRNA Delivery.

Federico Perche1,2, Swati Biswas1,2, Niravkumar R Patel1,2

  • 1Center for Pharmaceutical Biotechnology and Nanomedicine, School of Pharmacy, Bouve College of Health Sciences, Northeastern University, Boston, MA, USA.

Methods in Molecular Biology (Clifton, N.J.)
|November 5, 2015
PubMed
Summary

Researchers developed a novel hypoxia-responsive copolymer for targeted siRNA delivery in cancer therapy. This nanomedicine demonstrates enhanced cellular uptake and tumor accumulation, offering a promising approach for cancer treatment.

Keywords:
AzobenzeneStimuli-sensitiveTumor hypoxiaTumor targetingsiRNA delivery

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Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Oncology

Background:

  • Nanomedicine offers diverse strategies for cancer therapy.
  • Hypoxia is a common characteristic of solid tumors, influencing treatment efficacy.
  • Effective delivery of therapeutic agents like siRNA to tumors remains a challenge.

Purpose of the Study:

  • To synthesize and evaluate a hypoxia-responsive copolymer for siRNA delivery.
  • To investigate the copolymer's ability to condense siRNA and facilitate targeted delivery.
  • To assess the copolymer's performance in vitro and in vivo for cancer therapy.

Main Methods:

  • Synthesis of a polyethylene glycol-azobenzene-polyelectrolyte-lipid conjugate (PEG-Azo-PEI-DOPE) via coupling chemistry.
  • Evaluation of siRNA condensation and hypoxia-induced cellular internalization in vitro.
  • Assessment of reporter gene downregulation in cancer cell models.
  • In vivo studies in murine models to evaluate tumor accumulation after parenteral administration.

Main Results:

  • The PEG-Azo-PEI-DOPE copolymer successfully condensed siRNA.
  • Hypoxia-induced cellular internalization and reporter gene downregulation were observed in vitro.
  • The copolymer demonstrated significant tumor accumulation in vivo following parenteral administration.
  • Established procedures for evaluating hypoxia-targeted polymers in various cancer models were detailed.

Conclusions:

  • The developed hypoxia-responsive copolymer is a promising nanocarrier for siRNA delivery in cancer therapy.
  • The copolymer exhibits targeted cellular uptake and accumulation in tumors under hypoxic conditions.
  • This study provides a framework for evaluating hypoxia-targeted nanomedicines in preclinical cancer models.