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Modified-Release Drug Delivery Systems: Site-Targeted01:24

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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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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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In Vivo-Assembled Artificial Base-Albumin Platform for Tumor-Targeted General Drug Delivery.

Die Yu1,2, Shuangya Chen2, Mingxin Xu2

  • 1Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan 410082, China.

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This study introduces an innovative F-base modified oligonucleotide system for targeted cancer therapy. This platform enhances drug stability, tumor penetration, and efficacy, offering a promising approach to reduce chemotherapy side effects.

Keywords:
artificial baselong circulationtargeted deliverytumor accumulationtumor therapy

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Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Oncology

Background:

  • Chemotherapy causes severe side effects due to drug accumulation in healthy tissues.
  • Targeted drug delivery systems, like albumin-bound paclitaxel (nab-PTX), aim to mitigate these issues.
  • Fluorine-containing nucleobases (F-bases) show potential for albumin interaction in targeted delivery.

Purpose of the Study:

  • To assess an in vivo-assembled platform for tumor-targeted delivery of chemotherapeutics using F-base modified oligonucleotides.
  • To investigate the enhanced therapeutic potential of incorporating F-bases into drug-loaded DNA sequences.
  • To evaluate the efficacy and safety of this novel drug delivery system.

Main Methods:

  • Chemotherapeutic drugs (5-fluorouracil, gemcitabine, MMAE) were loaded onto DNA sequences.
  • F-bases were introduced at the ends of the drug-loaded DNA sequences.
  • The self-assembled nanostructures, F-drugs with albumin, were characterized, and their cytotoxicity, biodistribution, pharmacokinetics, therapeutic efficiency, and biosafety were analyzed in various tumor models.

Main Results:

  • F-base modification improved drug stability, in vitro cytotoxicity, and tumor cell penetrability.
  • The system demonstrated longer circulation times and higher tumor accumulation in preclinical models.
  • Significant improvements in antitumor effects were observed in CDX, PDX, and orthotopic tumor models.

Conclusions:

  • The F-based delivery system enhances chemotherapeutic solubility and tumor penetration.
  • This platform offers a promising strategy for improving targeted cancer therapy and reducing systemic toxicity.
  • Further development of F-base modified oligonucleotides could revolutionize chemotherapeutic drug delivery.