Multifunctional and multitargeted nanoparticles for drug delivery to overcome barriers of drug resistance in human cancers

Dawar, Swati; Singh, Neha; Kanwar, Rupinder K.; Kennedy, Richard L.; Veedu, Rakesh N.; Zhou, Shu‐Feng; Krishnakumar, Subramanian; Hazra, Sarbani; Sasidharan, Sreenivasan; Duan, Weigang; Kanwar, Jagat R.

doi:10.1016/j.drudis.2013.09.009

Cited by 54 publications

(34 citation statements)

References 76 publications

(81 reference statements)

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“…Several reports discussed the internalization of NPs into cells by endocytic pathways relevant to drug-efflux pump mechanism in the reversal MDR [22,23]. The mechanism was complicated and the endocytic pathway was different when endosome escape behavior was triggered by the combination strategy.…”

Section: Discussionmentioning

confidence: 98%

Synergistic effects of negative-charged nanoparticles assisted by ultrasound on the reversal multidrug resistance phenotype in breast cancer cells

Wang

Luo

Wen

et al. 2017

Ultrasonics Sonochemistry

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We have fabricated a negative-charged nanoparticle (Heparin-Folate-Tat-Taxol NP, H-F-Tat-T NP) with dual ligands, tumor targeting ligand folate and cell-penetrating peptide Tat, to deliver taxol presenting great anticancer activity for sensitive cancer cells, while it fails to overcome multidrug resistance (MDR) in MCF-7/T cells (taxol-resistant breast cancer cells). Ultrasound (US) can increase the sensitivity of positive-charged NPs thereby making it possible to reverse MDR through inducing NPs' drug release. However, compared with the negative-charged NPs, positive-charged NPs may cause higher toxic effect. Hence, the combination of negative-charged NPs and US may be an efficient strategy for overcoming MDR. The conventional procedure to treat with NPs followed by US exposure possibly destruct multifunctional NPs resulting in its bioactivity inhibition. Herein, we have further improved the operating approach to eliminate US mechanical damage and keep the integrity of negative-charged NPs: cells are exposed to US with microbubbles (MBs) prior to the treatment of H-F-Tat-T NPs. Superior to the conventional method, US sonoporation affects the physiological property of cancer cells while preventing direct promotion of drug release from NPs. The results of the present study displayed that US in condition (1MHz, 10% duty cycle, duration of 80s, US intensity of 0.6W/cm and volume ratio of medium to MBs 20:1) combined with H-F-T-Tat-T NPs can achieve optimal reversal MDR effect in MCF-7/T cells. Mechanism study further disclosed that the individual effect of US was responsible for the enhancement of cell membrane permeability, inhibition of cell proliferation rate and down-regulation of MDR-related genes and proteins. Simultaneously, US sonoporation on resistant cancer cells indirectly increased the accumulation of NPs by inducing endosomal escape of negative-charged NPs. Taken together, the overcoming MDR ability for the combined strategy was achieved by the synergistic effect from individual function of NPs, physiological changes of resistant cancer cells and behavior changes of NPs caused by US.

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Section: Discussionmentioning

confidence: 98%

Synergistic effects of negative-charged nanoparticles assisted by ultrasound on the reversal multidrug resistance phenotype in breast cancer cells

Wang

Luo

Wen

et al. 2017

Ultrasonics Sonochemistry

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“…The principal barrier to effective anticancer therapy is acquisition of natural (inherited) and acquired resistance [5,9,25]. Natural resistance is the unresponsiveness of a tumor towards an anticancer drug, whereas acquired resistance is unresponsiveness of tumors that develops over the time against chemotherapeutics that are initially effective [12, 22, 25]. Over the years, a large number of elements have been discovered as factors claimed for MDR in cancer [23].…”

Section: Mdr In Cancermentioning

confidence: 99%

“…They can be classified into two major categories; cellular and physiological factors. Cellular factors include molecular targets, genetic defects like polymorphisms and gene deletions, an over-expression of efflux pumps, reduced apoptosis and increased drug metabolism; while physiological factors include inter-cellular interactions, higher interstitial fluid pressure, a low pH environment, a hypoxic area within the tumor, irregular tumor vasculature, and the presence of cancer cells in areas difficult to penetrate [5,8,12,22-25]. …”

Section: Mdr In Cancermentioning

confidence: 99%

“…MDR targeted nanocarriers should optimally possess prolonged systemic circulation, reduced non-specific cellular uptake, active and passive targeting potential, controlled drug release, and multidrug encapsulation for instance for chemotherapeutic drugs, nucleic acids and inhibitors of MDR causing enzymes etc. [5,8,12,22-24]. The work presented here offers insight into the factors responsible for the MDR of cancer that eventually leads to the failure of chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Ahmad¹,

Akhter

Khan³

et al. 2016

CPD

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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.

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“…Developing special drug delivery systems based on nanotechnology has attracted great attention in the treatment of cancers during the last decades. 3,4 Nanocarriers such as liposomes, micelles and nanoparticles can achieve tumor-targeted delivery due to the enhanced permeability and retention (EPR) effect, or tumor-specific recognition to antibodies/ligands anchored on the surface of nanocarriers, 5 thereby reducing drug-induced systemic toxic effects. 6 The EPR effect refers to the enhanced permeability of nanoparticles across the tumor vascular barrier However, after internalization in tumor cells, nanoparticles are often trapped in endolysosomes and fail to deliver the payloads to their intracellular targets, thus significantly affecting the therapeutic efficacy of the drug.…”

Section: Introductionmentioning

confidence: 99%

Transferrin receptor-targeted pH-sensitive micellar system for diminution of drug resistance and targetable delivery in multidrug-resistant breast cancer

Gao

Duan

et al. 2017

IJN

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The emergence of drug resistance is partially associated with overproduction of transferrin receptor (TfR). To overcome multidrug resistance (MDR) and achieve tumor target delivery, we designed a novel biodegradable pH-sensitive micellar system modified with HAIYPRH, a TfR ligand (7pep). First, the polymers poly( l -histidine)-coupled polyethylene glycol-2000 (PHIS-PEG 2000 ) and 7pep-modified 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol-2000 (7pep-DSPE-PEG 2000 ) were synthesized, and the mixed micelles were prepared by blending of PHIS-PEG 2000 and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol-2000 (DSPE-PEG 2000 ) or 7pep-DSPE-PEG 2000 (7-pep HD micelles). The micelles exhibited good size uniformity, high encapsulation efficiency, and a low critical micelle concentration. By changing the polymer ratio in the micellar formulation, the pH response range was specially tailored to pH ~6.0. When loaded with antitumor drug doxorubicin (DOX), the micelle showed an acid pH-triggering drug release profile. The cellular uptake and cytotoxicity study demonstrated that 7-pep HD micelles could significantly enhance the intracellular level and antitumor efficacy of DOX in multidrug-resistant cells (MCF-7/Adr), which attributed to the synergistic effect of poly( l -histidine)-triggered endolysosom escape and TfR-mediated endocytosis. Most importantly, the in vivo imaging study confirmed the target-ability of 7-pep HD micelles to MDR tumor. These findings indicated that 7-pep HD micelles would be a promising drug delivery system in the treatment of drug-resistant tumors.

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Multifunctional and multitargeted nanoparticles for drug delivery to overcome barriers of drug resistance in human cancers

Cited by 54 publications

References 76 publications

Synergistic effects of negative-charged nanoparticles assisted by ultrasound on the reversal multidrug resistance phenotype in breast cancer cells

Synergistic effects of negative-charged nanoparticles assisted by ultrasound on the reversal multidrug resistance phenotype in breast cancer cells

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

Transferrin receptor-targeted pH-sensitive micellar system for diminution of drug resistance and targetable delivery in multidrug-resistant breast cancer

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