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Isolation of Proximal Fluids to Investigate the Tumor Microenvironment of Pancreatic Adenocarcinoma
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Microenvironment-sensing, nanocarrier-mediated delivery of combination chemotherapy for pancreatic cancer

Priyanka Ray1, Gauthami Nair2, Arnab Ghosh3,4

  • 1Department of Coatings and Polymeric Materials, North Dakota State University, Fargo, ND, 58108, USA.

Journal of Cell Communication and Signaling
|March 28, 2019
PubMed

Insights

This study developed a novel pH-sensing nanocarrier for co-delivering Gemcitabine (GEM) and an ERK inhibitor to treat pancreatic cancer, improving drug delivery and efficacy.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Oncology

Background:

  • Limited efficacy of current pancreatic cancer treatments necessitates novel therapeutic strategies.
  • Challenges in clinical translation of ERK inhibitors include off-target effects and toxicity.
  • Combination therapy with Gemcitabine (GEM) and ERK inhibitors shows promise but faces delivery hurdles.

Purpose of the Study:

  • To develop a pharmaceutical nanoformulation for co-delivery of GEM and an ERK inhibitor (SCH 772984).
  • To create a pH-sensing nanocarrier (NC) for controlled drug release and targeted delivery in pancreatic cancer.
  • To evaluate the feasibility of this combination therapy for improved pancreatic cancer treatment.

Main Methods:

  • Fabrication of a pH-sensing nanocarrier (NC) from a self-assembling triblock copolymer.
  • Co-stabilization of GEM (conjugated) and SCH 772984 (encapsulated) within the NC.
  • Characterization of NCs (hydrodynamic diameter: 161 nm) and assessment of drug loading content (GEM: 20.2%, SCH 772984: 18.3%).
  • Evaluation of pH-mediated drug release, cellular uptake, and anti-proliferative effects on pancreatic cancer cells.

Main Results:

  • Successfully developed a pH-sensing NC capable of co-delivering GEM and SCH 772984.
  • NCs demonstrated controlled drug release triggered by pH changes in the tumor microenvironment.
  • The nanoformulation effectively suppressed pancreatic cancer cell proliferation and showed accumulation at disease sites.
  • Demonstrated successful traffic through cellular membranes and engagement of target receptors.

Conclusions:

  • Co-delivery of GEM and an ERK inhibitor via a pH-sensing nanocarrier is feasible for pancreatic cancer treatment.
  • The developed NC platform offers a promising strategy for targeted drug delivery and overcoming challenges associated with combination chemotherapy.
  • This approach holds potential for enhanced therapeutic outcomes in pancreatic cancer by responding to the tumor microenvironment.
Keywords:
Drug deliveryExtracellular Receptor Kinase (ERK)NanocarrierPancreatic cancer

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