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Size-Transformable, Multifunctional Nanoparticles from Hyperbranched Polymers for Environment-Specific Therapeutic

Priyanka Ray, Lina Alhalhooly, Arnab Ghosh1,2

  • 1Cancer Research Unit, VA Medical Center, Kansas City, Missouri 64128, United States.

ACS Biomaterials Science & Engineering
|January 6, 2021
PubMed
Summary

New pH-responsive hyperbranched polymer nanocarriers selectively change size. These drug delivery systems show promise for treating pancreatic cancer by releasing therapeutics in response to tumor microenvironments.

Keywords:
biomaterialschemotherapy deliveryhyperbranched polymerspH-activationsize-modifiable nanoparticles

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Area of Science:

  • Polymer Science
  • Nanotechnology
  • Drug Delivery

Background:

  • Hyperbranched polymers offer unique structural properties for advanced applications.
  • Developing stimuli-responsive drug delivery systems is crucial for targeted therapies.

Purpose of the Study:

  • To synthesize and characterize pH-responsive hyperbranched polymer nanocarriers.
  • To evaluate their potential for drug delivery, particularly in pancreatic cancer.

Main Methods:

  • Synthesis of tertiary amine-conjugated polycarbonate blocks grafted from a hyperbranched polyester polyol core.
  • Dynamic light scattering, microscopy (TEM, AFM), and spectroscopy to assess pH-dependent size changes.
  • Loading of dye and drug molecules via noncovalent encapsulation and covalent conjugation.
  • In vitro studies on cellular uptake, cytotoxicity, and chemotherapeutic efficacy using gemcitabine in pancreatic cancer models.

Main Results:

  • Nanocarriers exhibited a reversible size change from 150-190 nm at neutral pH to 3-5 nm at lower pH due to protonation of tertiary amine groups.
  • Encapsulated payloads were rapidly released upon pH-induced disassembly, while conjugated payloads showed sustained release.
  • Assembled nanoparticles demonstrated biocompatibility, pH-dependent cellular uptake, and accumulation in 3D pancreatic cancer spheroids.
  • Gemcitabine-conjugated nanoparticles effectively suppressed cancer cell proliferation.

Conclusions:

  • Synthesized hyperbranched polymer nanocarriers are size-modifiable in response to pH.
  • These nanostructures show potential as smart biomaterials for targeted drug delivery in disease microenvironments like pancreatic cancer.
  • The pH-triggered size transformation and controlled release mechanisms offer a novel platform for therapeutic applications.