CRC the cause of MDR (8). Resistance

CRC is the third cause of the cancer-related
deaths in the United States, with an average lifetime risk of 5.1% as stated by
the American Cancer Society and the
Centre for Disease Control (CDC) (1, 2). CRC according to the progression of cancer
cells has been classified into five stages by the American Joint Committee on
Cancer (AJCC). At Stage 0, we will see 100% cure after surgery. Surgical
resection is also considered as the standard treatment for stages I–IIC. Stages
IIIA–IV patients are treated with adjuvant
chemotherapy following surgical resection, but because of the high probability
of metastasis, only 6% of them survive (3). Though
chemotherapy is a good option for CRC by far, it has many disadvantages.
Because of low specificity,
most of the chemotherapeutic drugs have
toxic side effects means these drugs cause much harm to healthy
cells as they kill the cancer cells (4, 5). In order to minimize the
severity of side effects, scientists have employed nanoparticle systems
for CRC therapy. due to this fact, they
have many benefits such as increasing drug-loaded nanoparticles accumulation in
the tumor cells because of enhanced permeability and retention (EPR) of
nanoparticles, and the capability of encapsulation delivery of poorly water-soluble drugs (6, 7). In spite of the progression of the
nanocarriers-based drug delivery systems, many problems still remain in
chemotherapy. In many cases, overexpressing drug-resistant genes is the cause
of MDR (8). Resistance can develop by multiple
mechanisms such as decreased drug uptake, pump the drugs out of the cells,
activation of detoxifying systems, activation of DNA repair pathways, the escape of drug-induced apoptosis, etc. (9, 10). As a consequence, we need a higher dose of drugs to obliterate the cancer
cells that can increase the adverse effects (11).

Recently nanocarrier-mediated
siRNA therapy has attracted a lot of attention in treating CRC (3, 12, 13) because of its capability to selectively
regulate the problematic genes that can be an alternative to chemotherapy. Moreover,
many studies have emerged, a combination
of chemotherapy and gene therapy through codelivery of anticancer drugs and
MDR-related siRNA as an innovative strategy for conquering MDR in CRC. In this
review, we present an overview of recent advances and challenges in
nanoparticle-based therapies for the treatment of CRC.

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