Applications of nanoparticle drug delivery systems for the reversal of multidrug resistance in cancer

Abstract

Abstract. Multidrug resistance (MDR) to chemotherapy presents a major obstacle in the treatment of cancer patients, which directly affects the clinical success rate of cancer therapy. Current research aims to improve the efficiency of chemotherapy, whilst reducing toxicity to prolong the lives of cancer patients. As with good biocompatibility, high stability and drug release targeting properties, nanodrug delivery systems alter the mechanism by which drugs function to reverse MDR, via passive or active targeting, increasing drug accumulation in the tumor tissue or reducing drug elimination. Given the potential role of nanodrug delivery systems used in multidrug resistance, the present study summarizes the current knowledge on the properties of liposomes, lipid nanoparticles, polymeric micelles and mesoporous silica nanoparticles, together with their underlying mechanisms. The current review aims to provide a reliable basis and useful information for the development of new treatment strategies of multidrug resistance reversal using nanodrug delivery systems. IntroductionAt present, chemotherapy remains the optimal choice for cancer therapy, and tumor multidrug resistance (MDR) is a major factor that reduces the efficacy of chemotherapy (1). MDR is a phenotype that tumor cells acquire, which confers resistance to certain chemotherapy drugs, as well as concurrent cross-resistance to additional antitumor drugs that have different structures or mechanisms of action (2,3). The complexity of MDR has impeded the study of reversal agents (3-5). In recent years, the application of nanotechnology for drug carrier design has resulted in the development of novel nanoparticle drug delivery systems that aim to reverse MDR (6-8). Inorganic nanodrug delivery systems, lipid-based systems and polymer nanodrug delivery systems are the most common nanodrug delivery systems, which exhibit non-toxic, biocompatible and highly stable properties (8,9). The application of nanoparticle drug delivery systems is increasing due to their advantage of controlled and targeted drug release (9,10). Studies have demonstrated that entrapped small molecule drugs (10-200 nm in diameter) are more conducive to drug uptake and efflux; these nanodrug particles function via passive and active mechanisms, whereas in the systemic blood circulation they exhibit sustained release that subsequently enhances intracellular drug accumulation in tumor cells, yielding an improved effect (1,(11)(12)(13)(14). In the present review, the application of nanoparticle drug delivery systems in reversing the MDR of tumors is reviewed, which may provide an improved understanding of novel strategies for cancer therapy. Applications of nanoparticle drug delivery systems for the reversal of multidrug resistance in cancer (Review)YINGHONG HUANG 1 , SUSAN P.C. COLE 2 , TIANGE CAI 3 , and YU CAI

Efficacious Doxorubicin Delivery Using Glutathione‐Responsive Hollow Non‐phospholipid Vesicles Bearing Lipoyl Cholesterols

“…This distinct activity of drug‐loaded vesicles in DR‐HeLa cells was also evaluated 4 h post‐treatment and it was observed that CL1V–DOX or CL2V–DOX treatment led to clearly visible intracellular DOX fluorescence, whereas treatment with the free drug did not cause cells to fluoresce (Figure 6a1 and a) . This can be plausibly ascribed to the ability of nanocarriers to bypass the drug‐efflux pumps on the membrane of drug‐resistant cells, which results in an increased intracellular concentration of drug . The drug internalisation study also helped in understanding the observed cytotoxicity against both drug‐sensitive and drug‐resistant cancer cells, which apparently relied upon the intracellular accumulation of drug .…”

“…Towards achieving these therapeutic goals, the development of bioresponsive nanocarriers that respond to either exogenous (e.g., changes in temperature and magnetic field) or endogenous (e.g., changes in pH and redox potential) stimuli has been rigorously studied over the last ten years . Bio‐responsive systems have the potential to address key issues in anticancer therapy, such as inefficient drug delivery, tumour‐cell‐specific targeting and the development of resistance to chemotherapeutic drugs . The existing plethora of drug transport vehicles is composed of several types of nano‐ and micro‐structured self‐assemblies of amphiphiles .…”

Nanotechnology Based Targeted Drug Delivery Systems in Breast Cancer Therapy

“…In cancer Pgp is over expressed and contributes to multi drug resistance by pumping chemotherapeutic drugs out of the cells. Because the Pgp transmembrane domain (TMD) is capable to identify chemically unrelated molecules and translocate them, mainly which are hydrophobic because ABC transporters permeates hydrophilic substances to pass through (Chang, 2003;Huang et al, 2016). More than 50% of cancer patients arises multi drug resistance.…”

Cholecalciferol-PEG Conjugate Based Nanomicelles of Doxorubicin for Treatment of Triple-Negative Breast Cancer

“…However, chemotherapy is associated with the unavoidable side effects, leading to toxicity to patients and development of drug resistance (1–4). The development of advanced drug delivery systems has shown great potential to yield enhanced therapeutic efficacy and comparatively higher accumulation of drug in tumor cells along with minimal exposure to normal tissues (1,5,6). However, the development of multidrug resistance (MDR) in cancer cells is of grave concern, limiting the efficacy of anticancer agents and, hence, the failure of therapy.…”

“…However, the development of multidrug resistance (MDR) in cancer cells is of grave concern, limiting the efficacy of anticancer agents and, hence, the failure of therapy. Several biochemical changes have been described to be involved for the development of MDR (5–7). Overexpression of ATP-binding cassette transporters causing efflux of drug, overexpression of P-glycoprotein (P-gp), multidrug resistance-associated proteins (MRP1, MRP2), and breast cancer resistance protein (BCRP) are some of the major mechanisms reported to be involved in the development of MDR (6–8).…”