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Synergism is a useful mechanism where combining two or more drugs is more effective than each constituent used alone. Such combinations are also called supra-additive interactions. The drugs collectively enhance the final therapeutic effect by acting on different targets. Another advantage is that the low dose of each constituent drug is sufficient to achieve the desired effect. This helps reduce the duration of therapy and lower the adverse effects of these drugs.
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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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Synergistic chemo-photodynamic therapy by "big & small combo nanoparticles" sequential release system.

Li Fan1, Saisai Zhao2, Xin Jin3

  • 1Department of Pharmaceutical analysis, The Fourth Military Medical University, Xi'an, Shaanxi, China.

Nanomedicine : Nanotechnology, Biology, and Medicine
|September 20, 2017
PubMed
Summary

This study introduces novel big & small combo nanoparticles (NPbig&small) for enhanced cancer therapy. These nanoparticles deliver methylene blue (MB) and Gemcitabine hydrochloride (GM·HCl) sequentially, improving therapeutic efficacy.

Keywords:
CancerChemo-photodynamic therapyNanoparticlesSequential releaseSilicon

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Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Cancer Therapy

Background:

  • Chemo-photodynamic therapy offers synergistic potential for cancer treatment.
  • Sequential drug release from photosensitizers (PSs) can significantly enhance therapeutic outcomes.

Purpose of the Study:

  • To develop a "big & small combo nanoparticles (NPbig&small)" system for co-delivery of methylene blue (MB) and Gemcitabine hydrochloride (GM·HCl).
  • To investigate the sequential release profile of MB and its impact on GM·HCl efficacy.
  • To evaluate the in vitro and in vivo synergistic efficacy of the NPbig&small system.

Main Methods:

  • Fabrication of NPbig&small for double loading of MB and GM·HCl.
  • Characterization of sequential release kinetics using TEM and mathematical modeling.
  • Assessment of Enhanced Permeability and Retention (EPR) effect.
  • In vitro and in vivo evaluation of synergistic chemo-photodynamic therapy.

Main Results:

  • NPbig&small exhibited a two-peak sequential release profile for MB, enhancing GM·HCl's chemotherapeutic efficacy.
  • Morphological evolution confirmed sequential release in aqueous and cellular environments.
  • Demonstrated significant EPR effect and improved synergistic efficacy in vitro and in vivo.

Conclusions:

  • The NPbig&small system facilitates programmable sequential release of therapeutic agents.
  • This platform shows promise for enhanced synergistic chemo-photodynamic cancer treatment.
  • Sequential release mechanism is key to improving drug efficacy and therapeutic outcomes.