Engineered Nanoparticles Against MDR in Cancer: The State of the Art and its Prospective

Abstract

Cancer is a highly heterogeneous disease, both within a single patient as well as between patients, and is the leading cause of death worldwide. A variety of mono and combinational therapies, including chemotherapy, have been developed and refined over recent years for its effective treatment. However, the evolution of chemotherapeutic resistance or multidrug resistance (MDR) in cancer has become a major challenge to successful chemotherapy. MDR is a complex process that combines multifaceted non-cellular and cellular-based mechanisms. Research in the area of cancer nanotechnology over the past two decades has reached the point where smartly designed nanoparticles with targeting ligands can aid successful chemotherapy by preferentially accumulating within the tumor region through means of active and passive targeting to overcome MDR, and simultaneously reduce the off-target accumulation of their payload. Such nanoparticle formulations – sometimes termed nanomedicines - are at different stages of cancer clinical trials and show promise in resistant cases. Nanoparticles as chemotherapeutics carriers provide the opportunity to have multiple payloads of drug and/or imaging agents for combinational and theranostic therapy. Moreover, nanotechnology has the potential to combine new treatment strategies, such as near-infrared (NIR), magnetic resonance imaging (MRI), and high intensity focused ultrasound (HIFU) into cancer chemotherapy and imaging. Here we discuss the cellular/non-cellular factors that underpin MDR in cancer, and the potential of nanomedicines to combat MDR, along with recent advances in combining nanotechnology with other approaches in cancer therapy.

The Effect of Nanosystems on ATP-Binding Cassette Transporters: Understanding the Influence of Nanosystems on Multidrug Resistance Protein-1 and P-glycoprotein

“…Downregulating MDR genes and delivering anti-cancer drugs at the same time can be achieved using polymeric nanoparticles [74]. For instance, coformulation of curcumin and doxorubicin in PLGA downregulated the expression of P-gp/MDR1 and BCL-2 helping DOX accumulate in leukemic cells [75].…”

Exosome-Based Cancer Therapy: Implication for Targeting Cancer Stem Cells

“…In recent years, some synthetic nanoparticles have been employed as vehicles to deliver therapeutic drugs to the bulk of the tumor, and even directly target CSCs (Lu et al, 2016). Nanoparticles also have slow drug-releasing characteristics which induce a sustained high local drug concentration around the tumor and an enhanced anti-cancer efficiency (Ahmad et al, 2016; Piktel et al, 2016). As recently reviewed by Lu et al several synthetic nanoparticles, such as liposomes, niosomes, micelles, polymeric, and gold nanoparticles are able to deliver anticancer drugs to target tumor cells; this precision is made possible by their ability to use CSC specific markers such as CD44, CD90, and CD133 to target a specific population.…”

Multifunctional Shell–Core Nanoparticles for Treatment of Multidrug Resistance Hepatocellular Carcinoma

“…Actually, synergistic administration of drug‐resistance inhibitor and antitumor agent is a traditional classic approach to treating MDR tumor cells. Moreover, nanocarrier drug particles can antagonize and offset the tumor cells' active efflux effect through altering the internalization pathway and extending the retention time in MDR tumor cells …”