Overcoming drug efflux-based multidrug resistance in cancer with nanotechnology

Abstract

Multidrug resistance (MDR), which significantly decreases the efficacy of anticancer drugs and causes tumor recurrence, has been a major challenge in clinical cancer treatment with chemotherapeutic drugs for decades. Several mechanisms of overcoming drug resistance have been postulated. Well known P-glycoprotein (P-gp) and other drug efflux transporters are considered to be critical in pumping anticancer drugs out of cells and causing chemotherapy failure. Innovative theranostic (therapeutic and diagnostic) strategies with nanoparticles are rapidly evolving and are anticipated to offer opportunities to overcome these limits. In this review, we discuss the mechanisms of drug efflux-mediated resistance and the application of multiple nanoparticle-based platforms to overcome chemoresistance and improve therapeutic outcome.

Nanomedicine therapeutic approaches to overcome cancer drug resistance

“…Initially, patients may have either a partial or complete response to the first line of treatment but eventually exhibit cancer progression or recurrence. With repeated treatment, tumors often become resistant not only to the specific chemotherapeutic agent being employed, but cross-resistant to both similar and structurally unrelated classes of cytotoxic drugs [16-18]. …”

Multiple cues on the physiochemical, mesenchymal, and intracellular trafficking interactions with nanocarriers to maximize tumor target efficiency

“…Efflux pump proteins (eg, ABC transporters) are commonly overexpressed in tumor cells, which promote efflux of the cancer drug from the cytosol to outside the cell membrane. [139][140][141][142] Endosomal drug delivery can bypass this drug efflux activity, generate greater amounts of endosomes that encapsulate the nanodrugs, and, ultimately, maximize therapeutic efficacy by safely delivering uptaken drugs to the targeted organelles (ie, the nucleus or mitochondria). Previous reviews have discussed cellular uptake of nanosized vectors via dynamin-dependent or -independent pathways, where the uptaken agents mostly experienced endosomal and lysosomal degradation.…”

Thyroid Stem Cells: Concept and Clinical Implications

“…Using the SP assay, SC have been successfully isolated from benign and malignant thyroid tissues and cells lines (42,58). There have been approaches involving nanoparticle administration aimed at inhibiting the activity of these transporters as means of overcoming drug resistance in cancer cells (59).…”