Introduction

Pancreatic ductal adenocarcinoma (PDAC) remains as one of the leading causes of global cancer-related death with a median survival of six months after diagnosis (Ilic & Ilic, 2016; Kamisawa, Wood, Itoi, & Takaori, 2016). Depending on the stage and patterns of tumor growth and patient characteristics, different treatment strategies such as radiation therapy (RT), chemotherapy (alone or in combination) and surgery have been developed for the pancreatic tumor therapy (Kami et al., 2005; Kleeff et al., 2016). Adjuvant chemotherapy after surgical resection is the treatment of choice for the early stages of the disease. In spite of progress in the detecting, managing, and treating techniques of pancreatic cancer, the five-year survival rate only reaches to around 9%. Two combination chemotherapy regimens including 5-fluorouracil (5-FU)/leucovorin with irinotecan and oxaliplatin (FOLFIRINOX), and gemcitabine (GEM) with nab-paclitaxel are currently the gold standard treatments for fmametastatic pancreatic cancer. Although these strategies improved the prognosis of advanced pancreatic cancer, short half-life of drugs in blood, non-specific toxicity, and multidrug resistance (MDR) still cause poor clinical outcomes (Cives & Strosberg, 2018; Wolfgang et al., 2013).
In recent years, siRNA-based therapeutics have emerged as revolutionary therapeutic modalities for the treatment of human diseases, especially malignant cancers, by selectively targeting disease-causing genes. Furthermore, the combination of siRNA-based therapeutic agents with conventional anti-cancer drugs can represent a new powerful strategy to overcome MDR and pancreatic cancer (Oh & Park, 2009). Despite its great potential, In vivo siRNA-based therapy faces major challenges including poor cellular uptake, off-target effects, enzymatic degradation, immune recognition, and rapid clearance (C. I. E. Smith & Zain, 2019).
To address these limitations, nanoparticle-based carriers make the targeted delivery of siRNAs and chemotherapeutic agents possible through effective and safe means (Shahin Aghamiri, Keyvan Fallah Mehrjardi, et al., 2019). Because of their enhanced permeability and retention (EPR), these carriers are potential choices for delivery of poorly soluble medications, encapsulation and preferential accumulation and concentration of drug-loaded nanocarriers in the tumor cells (Riley, June, Langer, & Mitchell, 2019). Altogether, nanoparticle-based delivery, chemotherapy, and siRNAs are practical strategies that can represent an exciting potential class of therapeutic agents to resensitize pancreatic tumor cells and facilitate pancreatic tumor therapy. Here, we present an overview of new achievements and limitations in designing novel nanocarrier-based therapeutic approaches for the treatment pancreatic malignancies. Moreover, proposed methods for the delivery of chemotherapy drugs and/or imaging agents with siRNA for synergistic anti-pancreatic cancer properties will be reviewed.