Exploring new Horizons in overcoming P-glycoprotein-mediated multidrug-resistant breast cancer via nanoscale drug delivery platforms

Abstract

The high probability (13%) of women developing breast cancer in their lifetimes in America is exacerbated by the emergence of multidrug resistance after exposure to first-line chemotherapeutic agents. Permeation glycoprotein (P-gp)-mediated drug efflux is widely recognized as the major driver of this resistance. Initial in vitro and in vivo investigations of the co-delivery of chemotherapeutic agents and P-gp inhibitors have yielded satisfactory results; however, these results have not translated to clinical settings. The systemic delivery of multiple agents causes adverse effects and drug–drug interactions, and diminishes patient compliance. Nanocarrier-based site-specific delivery has recently gained substantial attention among researchers for its promise in circumventing the pitfalls associated with conventional therapy. In this review article, we focus on nanocarrier-based co-delivery approaches encompassing a wide range of P-gp inhibitors along with chemotherapeutic agents. We discuss the contributions of active targeting and stimuli responsive systems in imparting site-specific cytotoxicity and reducing both the dose and adverse effects.

PEGylated Liposomes Remotely Loaded with the Combination of Doxorubicin, Quinine, and Indocyanine Green Enable Successful Treatment of Multidrug-Resistant Tumors

“…In the current study, the liposomal doxorubicin was not toxic to HT-29 MDR1 cells (Figure 4b), similarly to free doxorubicin (Figure 3a). It was suggested in the literature that in vivo liposomal doxorubicin improved the outcome of resistant tumors due to modified pharmacokinetics parameters and the high bioavailability of the liposomal doxorubicin [51]. However, the HT-29 MDR1 resistant cells viability was decreased only in the presence of P-gp inhibitor quinine (Figure 4d).…”

Combination of Antimalarial and CNS Drugs with Antineoplastic Agents in MCF-7 Breast and HT-29 Colon Cancer Cells: Biosafety Evaluation and Mechanism of Action

“…P-gp, also known as multidrug resistance protein (MDR1), is an adenosine triphosphate (ATP) binding cassette transporter (ABCB1) that is expressed in the cell membrane and is involved in the efflux of drugs to the outside of cells, contributing to the development of drug resistance [ 35 ]. Many types of cancer overexpress Pgp which prevents cancer drugs from reaching their cellular targets [ 36 ].…”

Tuning Mesoporous Silica Nanoparticles in Novel Avenues of Cancer Therapy

“…P-glycoproteins present on the cell surface play an important role in developing multidrug resistance by reducing drug concentration within the tumor cells through the drug efflux mechanism. 5 Liu and colleagues developed paclitaxel and quercetin coloaded MSN nanoparticles for breast cancer multidrug resistance, whereas quercetin was used as a P-glycoprotein inhibitor. They coated the coloaded MSN with chondroitin sulfate, which has been reported to recognize the overexpressed CD44 receptors of tumor cells.…”

“…3 Conventional chemotherapy also lacks target specificity while increasing the likelihood of drug−drug interactions, chemoresistance, therapeutic failure against metastasis, recurrence, and poor efficacy against circulating tumor cells. 4,5 At the moment, researchers are looking into new ways to deliver peptides and genes to get around some of the problems with traditional therapy. 6 Although these avenues possess good targeting ability, they suffer from pitfalls such as rapid enzymatic degradation, diminished half-life, and poor accumulation at the bioactive site.…”