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.