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Synergistic triple-combination therapy with hyaluronic acid-shelled PPy/CPT nanoparticles results in tumor regression and prevents tumor recurrence and metastasis in 4T1 breast cancer.

Abstract
Breast cancer is characterized by high aggression, poor prognosis, and high recurrence rate. Early detection and specific targeted treatment with less toxicity are the ultimate goals for breast cancer therapy. To improve antitumor therapeutic effects, we developed a novel polypyrrole nanoparticle using the near infrared dye IRDye800CW with camptothecin (CPT)-conjugated hyaluronic acid (HA) shell (PPy@CPT-HA-IRDye800CW) and performed a photothermal therapy (PTT), along with chemotherapy, guided by fluorescence and photoacoustic dual-modality imaging, in combination with immunotherapy. Irradiation with near infrared (NIR) light offered a strong PTT effect and promoted CPT drug release in tumors. Moreover, we found that chemo-photothermal therapy with PPy@CPT-HA-IRDye800CW NPs, in combination with immune checkpoint inhibitor anti-PD-L1 immunotherapy, synergistically enhanced the anti-tumor immune response, thereby eliminating primary breast cancer and preventing tumor metastases and recurrences in 4T1 tumor-bearing mice. This approach may provide important clues for the clinical management of breast cancer and other malignant tumors.
AuthorsWei Sun, Yang Du, Xiaolong Liang, Chunyao Yu, Junjie Fang, Wei Lu, Xiuyu Guo, Jie Tian, Yinhua Jin, Jianjun Zheng
JournalBiomaterials (Biomaterials) Vol. 217 Pg. 119264 (10 2019) ISSN: 1878-5905 [Electronic] Netherlands
PMID31260883 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.
Chemical References
  • Polymers
  • Pyrroles
  • polypyrrole
  • Hyaluronic Acid
  • Camptothecin
Topics
  • Animals
  • Camptothecin (therapeutic use)
  • Cell Line, Tumor
  • Combined Modality Therapy
  • Female
  • Fluorescence
  • Hyaluronic Acid (chemistry)
  • Hyperthermia, Induced
  • Immunity
  • Immunotherapy
  • Mammary Neoplasms, Animal (drug therapy, immunology, pathology)
  • Mice
  • Nanoparticles (chemistry, ultrastructure)
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local (prevention & control)
  • Optical Imaging
  • Photoacoustic Techniques
  • Phototherapy
  • Polymers (chemistry)
  • Pyrroles (chemistry)
  • Tissue Distribution

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