Targeted dual intervention-oriented drug-encapsulated (Diode) nanoformulations for improved treatment of pancreatic cancer

Vijay Sagar Madamsetty, Krishnendu Pal, Shamit Kumar Dutta, Enfeng Wang, Debabrata Mukhopadhyay

Research output: Contribution to journalArticlepeer-review

Abstract

Despite recent advancements, effective treatment for pancreatic ductal adenocarcinoma (PDAC) has remained elusive. The overall survival rate in PDAC patients has been dismally low due to resistance to standard therapies. In fact, the failure of monotherapies to provide long-term survival benefits in patients led to ascension of several combination therapies for PDAC treatment. However, these combination therapies provided modest survival improvements while increasing treatment-related adverse side effects. Hence, recent developments in drug delivery methods hold the potential for enhancing therapeutic benefits by offering cocktail drug loading and minimizing chemotherapy-associated side effects. Nanoformulations-aided deliveries of anticancer agents have been a success in recent years. Yet, improving the tumor-targeted delivery of drugs to PDAC remains a major hurdle. In the present paper, we developed several new tumor-targeted dual intervention-oriented drug-encapsulated (DIODE) liposomes. We successfully formulated liposomes loaded with gemcitabine (G), paclitaxel (P), erlotinib (E), XL-184 (c-Met inhibitor, X), and their combinations (GP, GE, and GX) and evaluated their in vitro and in vivo efficacies. Our novel DIODE liposomal formulations improved median survival in comparison with gemcitabine-loaded liposomes or vehicle. Our findings are suggestive of the importance of the targeted delivery for combination therapies in improving pancreatic cancer treatment.

Original languageEnglish (US)
Article number1189
JournalCancers
Volume12
Issue number5
DOIs
StatePublished - May 2020

Keywords

  • Gemcitabine
  • Liposomes
  • Nanoformulations
  • Pancreatic cancer
  • Targeted drug delivery

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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