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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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Targeted Cancer Therapies02:57

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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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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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Biodegradable polymersomes encapsulating copper peroxide and gemcitabine for targeted chemoimmunotherapy.

Man Lung Lee1, Weiwei Jiang2, Jack Chun Hin Chen3

  • 1Department of Chemistry, The Chinese University of Hong Kong, Hong Kong, China.

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This study introduces novel nanoparticles that combine chemotherapy and immunotherapy to treat triple-negative breast cancer. These nanoparticles enhance treatment efficacy by generating reactive oxygen species (ROS) to boost anti-PD-L1 immunotherapy.

Keywords:
Chemodynamic therapyCold tumorImmunotherapyMetal peroxide

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Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Cancer Therapy

Background:

  • Triple-negative breast cancer (TNBC) exhibits resistance to conventional therapies.
  • Developing targeted drug delivery systems is crucial for effective cancer treatment.
  • Immunotherapy shows promise but faces challenges in overcoming the tumor microenvironment (TME).

Purpose of the Study:

  • To engineer ROS-responsive polymersomes (HA-PGC) for targeted TNBC therapy.
  • To combine chemodynamic therapy with immunotherapy for enhanced anti-cancer effects.
  • To overcome resistance in TNBC by converting cold tumors into hot tumors.

Main Methods:

  • Fabrication of hyaluronic acid-functionalized polymersomes (HA-PGC) encapsulating gemcitabine (GEM) and copper peroxide nanoparticles (CuO₂).
  • Utilizing CuO₂ decomposition in the acidic TME to generate ROS via Fenton-like reactions.
  • Assessing the synergistic effects of ROS on gemcitabine activation, glutathione depletion, and immunogenic cell death (ICD).
  • Evaluating the combined efficacy of HA-PGC nanoparticles and anti-PD-L1 immunotherapy in a TNBC model.

Main Results:

  • HA-PGC nanoparticles effectively targeted CD44-overexpressing TNBC cells.
  • Induced ROS suppressed cytidine deaminase (CDA), enhancing GEM activation, and depleted glutathione (GSH), reducing ROS scavenging.
  • Oxidative stress promoted ICD, dendritic cell maturation, and increased tumor-infiltrating lymphocytes.
  • The nanoparticle platform converted cold tumors to hot tumors, significantly improving anti-PD-L1 immunotherapy efficacy.

Conclusions:

  • A novel multifunctional nanoparticle platform combining chemodynamic therapy and immunotherapy was demonstrated.
  • This strategy shows promise for overcoming resistance in triple-negative breast cancer treatment.
  • The findings provide a foundation for designing intelligent immunotherapeutic systems.