Nanodrug delivery in reversing multidrug resistance in cancer cells

Abstract

Different mechanisms in cancer cells become resistant to one or more chemotherapeutics is known as multidrug resistance (MDR) which hinders chemotherapy efficacy. Potential factors for MDR includes enhanced drug detoxification, decreased drug uptake, increased intracellular nucleophiles levels, enhanced repair of drug induced DNA damage, overexpression of drug transporter such as P-glycoprotein(P-gp), multidrug resistance-associated proteins (MRP1, MRP2), and breast cancer resistance protein (BCRP). Currently nanoassemblies such as polymeric/solid lipid/inorganic/metal nanoparticles, quantum dots, dendrimers, liposomes, micelles has emerged as an innovative, effective, and promising platforms for treatment of drug resistant cancer cells. Nanocarriers have potential to improve drug therapeutic index, ability for multifunctionality, divert ABC-transporter mediated drug efflux mechanism and selective targeting to tumor cells, cancer stem cells, tumor initiating cells, or cancer microenvironment. Selective nanocarrier targeting to tumor overcomes dose-limiting side effects, lack of selectivity, tissue toxicity, limited drug access to tumor tissues, high drug doses, and emergence of multiple drug resistance with conventional or combination chemotherapy. Current review highlights various nanodrug delivery systems to overcome mechanism of MDR by neutralizing, evading, or exploiting the drug efflux pumps and those independent of drug efflux pump mechanism by silencing Bcl-2 and HIF1α gene expressions by siRNA and miRNA, modulating ceramide levels and targeting NF-κB. “Theragnostics” combining a cytotoxic agent, targeting moiety, chemosensitizing agent, and diagnostic imaging aid are highlighted as effective and innovative systems for tumor localization and overcoming MDR. Physical approaches such as combination of drug with thermal/ultrasound/photodynamic therapies to overcome MDR are focused. The review focuses on newer drug delivery systems developed to overcome MDR in cancer cell.

A highly tumor-targeted nanoparticle of podophyllotoxin penetrated tumor core and regressed multidrug resistant tumors

“…Nanoparticle (NP) drug delivery system has been postulated to enhance activity of standard drugs such as taxanes and anthracyclines against MDR tumors by modulating the cellular uptake pathway [11]. It is hypothesized that NPs can carry drugs into an MDR cell via cellular endocytosis, bypassing the Pgp mediated drug efflux, and thus enhancing the drug activity.…”

Multidrug Resistance in Cancer Circumvented Using a Cytosolic Drug Reservoir

“…This explained the decreasing trend of Dox concentration in MDA LCC6 cells in the first two hours (Figure 3a). On the other hand, MDA LCC6 MDR1 cells overexpressed with P‐gp,25 leading to efficient efflux of Dox out of cells. Consistently, one observed both the significantly reduced cellular uptake of free Dox (Figure 2f) in MDA LCC6 MDR1 cells, and its significant concentration decrease with further incubation in drug free medium (Figure 3b) for the first two hours.…”

Biocompatibility of Bare Nanoparticles Based on Silicon and Gold for Nervous Cells

“…Due to small size and unique properties, such type of NPs can penetrate deeply into tissues, cells and nuclei, which is promising for theranostics (simultaneous therapy and diagnostics) of cancer [1]. NPs are considered as agents for a number of optical imaging techniques, carriers of drugs and their controlled release, as well as targets for directed tumor cells destruction by physical actions [2][3][4].…”