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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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Site-targeted drug delivery systems enhance therapeutic efficacy while minimizing systemic toxicity and treatment costs. Unlike conventional methods, these systems ensure precise drug delivery, improving bioavailability and reducing side effects. Targeted drug delivery is classified into three levels. First-order targeting directs drugs to the capillary beds of specific organs or tissues. Second-order targets specific cell types, such as tumor cells, using receptor-mediated interactions.
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Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
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The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
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Related Experiment Video

Updated: Mar 30, 2026

Preparation of Neutrally-charged, pH-responsive Polymeric Nanoparticles for Cytosolic siRNA Delivery
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Tumor Acidity-Sensitive Polymeric Vector for Active Targeted siRNA Delivery.

Chun-Yang Sun1, Song Shen1, Cong-Fei Xu2

  • 1The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science & Technology of China , Hefei, Anhui 230027, PR China.

Journal of the American Chemical Society
|November 17, 2015
PubMed
Summary

New nanovectors detach their protective shells in tumors, enhancing siRNA delivery. This approach overcomes PEGylation

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Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Drug Delivery

Background:

  • Surface PEGylation of siRNA vectors prevents protein adsorption and RES clearance but hinders cellular uptake.
  • Stimuli-responsive, shell-detachable nanovectors offer a solution for enhanced cellular internalization and prolonged circulation.
  • Tumor extracellular pH (pHe) is a promising stimulus, but designing sensitive systems is challenging due to subtle pH differences.

Purpose of the Study:

  • To develop a novel acid-sensitive bridged copolymer for tumor-targeted systemic delivery of siRNA.
  • To create stimuli-responsive nanovectors that enhance cellular uptake while maintaining prolonged blood circulation.
  • To overcome the dilemma of PEGylation's dual effect on siRNA vector performance.

Main Methods:

  • Development of a simple acid-sensitive bridged copolymer.
  • Formation of micelleplex delivery systems (Dm-NP) with a poly(ethylene glycol) (PEG) corona.
  • Incorporation of a pH-responsive linkage for PEG detachment and a cell-penetration peptide for enhanced uptake.

Main Results:

  • Dm-NP demonstrated a stable PEG corona for prolonged circulation and RES evasion.
  • Acid-sensitive linkage breakage at tumor sites triggered PEG detachment, facilitating cell targeting.
  • Exposure of cell-penetration peptide upon PEG removal significantly enhanced cellular uptake.
  • Dm-NP achieved effective tumor accumulation and enhanced inhibition of non-small cell lung cancer growth.

Conclusions:

  • The developed Dm-NP system successfully balances prolonged circulation and targeted cellular delivery.
  • Stimuli-responsive PEG detachment is a viable strategy for enhancing nanovector efficacy in tumors.
  • This approach offers a safe and effective method for siRNA delivery and cancer treatment.