Multifunctional nanoplatforms co-delivering combinatorial dual-drug for eliminating cancer multidrug resistance

Xiao, Wei; Song, Mingxin; Li, Weijie; Huang, Jing; Yang, Guang; Wang, Yi

doi:10.7150/thno.59342

Cited by 31 publications

(30 citation statements)

References 142 publications

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“…Many studies and considerable efforts have been devoted to exploring combination therapy; in particular, simultaneous delivery of genes and chemotherapy drugs presents a remarkable potential to enhance antitumor activity [ 51 ]. Using MCF-7 xenograft models, we further evaluated the synergistic antitumor efficacy of D-L H /si-DTX.…”

Section: Resultsmentioning

confidence: 99%

Multistage pH-responsive codelivery liposomal platform for synergistic cancer therapy

et al. 2022

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Background Small interfering RNA (siRNA) is utilized as a potent agent for cancer therapy through regulating the expression of genes associated with tumors. While the widely application of siRNAs in cancer treatment is severely limited by their insufficient biological stability and its poor ability to penetrate cell membranes. Targeted delivery systems hold great promise to selectively deliver loaded drug to tumor site and reduce toxic side effect. However, the elevated tumor interstitial fluid pressure and efficient cytoplasmic release are still two significant obstacles to siRNA delivery. Co-delivery of chemotherapeutic drugs and siRNA represents a potential strategy which may achieve synergistic anticancer effect. Herein, we designed and synthesized a dual pH-responsive peptide (DPRP), which includes three units, a cell-penetrating domain (polyarginine), a polyanionic shielding domain (ehG)n, and an imine linkage between them. Based on the DPRP surface modification, we developed a pH-responsive liposomal system for co-delivering polo-like kinase-1 (PLK-1) specific siRNA and anticancer agent docetaxel (DTX), D-Lsi/DTX, to synergistically exhibit anti-tumor effect. Results In contrast to the results at the physiological pH (7.4), D-Lsi/DTX lead to the enhanced penetration into tumor spheroid, the facilitated cellular uptake, the promoted escape from endosomes/lysosomes, the improved distribution into cytoplasm, and the increased cellular apoptosis under mildly acidic condition (pH 6.5). Moreover, both in vitro and in vivo study indicated that D-Lsi/DTX had a therapeutic advantage over other control liposomes. We provided clear evidence that liposomal system co-delivering siPLK-1 and DTX could significantly downregulate expression of PLK-1 and inhibit tumor growth without detectable toxic side effect, compared with siPLK-1-loaded liposomes, DTX-loaded liposomes, and the combinatorial administration. Conclusion These results demonstrate great potential of the combined chemo/gene therapy based on the multistage pH-responsive codelivery liposomal platform for synergistic tumor treatment. Graphical Abstract

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Section: Resultsmentioning

confidence: 99%

Multistage pH-responsive codelivery liposomal platform for synergistic cancer therapy

et al. 2022

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“…Polymeric nanoparticles provide sustained release of drugs, prevent drug metabolism and detoxification and have a long circulation time, avoiding clearance from the system and enhancing uptake within cells [ 98 ]. Many polymeric nanoparticles loaded with chemotherapeutic drugs and P-gp inhibitors have been studied to modulate ABC efflux transporters and enhance the intracellular accumulation of anticancer drugs in MDR tumor cells [ 99 – 101 ]. Le and co-workers, for example, evaluated doxorubicin-loaded liponanoparticles (LNPs) in order to bypass the P-gp efflux mechanism in doxorubicin-resistant MCF-7/ADR breast cancer cells.…”

Section: Nanocarrier-based Drug Delivery Systems To Overcome Mdrmentioning

confidence: 99%

Emerging nanotechnology-based therapeutics to combat multidrug-resistant cancer

2022

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Cancer often develops multidrug resistance (MDR) when cancer cells become resistant to numerous structurally and functionally different chemotherapeutic agents. MDR is considered one of the principal reasons for the failure of many forms of clinical chemotherapy. Several factors are involved in the development of MDR including increased expression of efflux transporters, the tumor microenvironment, changes in molecular targets and the activity of cancer stem cells. Recently, researchers have designed and developed a number of small molecule inhibitors and derivatives of natural compounds to overcome various mechanisms of clinical MDR. Unfortunately, most of the chemosensitizing approaches have failed in clinical trials due to non-specific interactions and adverse side effects at pharmacologically effective concentrations. Nanomedicine approaches provide an efficient drug delivery platform to overcome the limitations of conventional chemotherapy and improve therapeutic effectiveness. Multifunctional nanomaterials have been found to facilitate drug delivery by improving bioavailability and pharmacokinetics, enhancing the therapeutic efficacy of chemotherapeutic drugs to overcome MDR. In this review article, we discuss the major factors contributing to MDR and the limitations of existing chemotherapy- and nanocarrier-based drug delivery systems to overcome clinical MDR mechanisms. We critically review recent nanotechnology-based approaches to combat tumor heterogeneity, drug efflux mechanisms, DNA repair and apoptotic machineries to overcome clinical MDR. Recent successful therapies of this nature include liposomal nanoformulations, cRGDY-PEG-Cy5.5-Carbon dots and Cds/ZnS core–shell quantum dots that have been employed for the effective treatment of various cancer sub-types including small cell lung, head and neck and breast cancers. Graphical Abstract

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“…It has been proven that the mechanisms of tumor multidrug resistance mainly include ATP-dependent drug efflux, DNA repair, inhibition of the apoptosis pathway, and tumor tissue heterogeneity in recent years ( Figure 1 ) ( Shapira et al, 2011 ; Housman et al, 2014 ; Bar-Zeev et al, 2017 ; Wei et al, 2021 ). In addition to that, the hypoxic tumor microenvironment ( Zeng et al, 2015 ; Jing et al, 2019 ), cancer stem cell regulation ( Donnenberg and Donnenberg, 2005 ; Mihanfar et al, 2019 ), endoplasmic reticulum stress ( Bahar et al, 2019 ), and the immune suppression microenvironment of tumors ( Vasan et al, 2019 ) were also proven to be closely related to the progress of MDR.…”

Section: Introductionmentioning

confidence: 99%

Recent Progress of Novel Nanotechnology Challenging the Multidrug Resistance of Cancer

Zhang

Han

et al. 2022

Front. Pharmacol.

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Multidrug resistance (MDR) of tumors is one of the clinical direct reasons for chemotherapy failure. MDR directly leads to tumor recurrence and metastasis, with extremely grievous mortality. Engineering a novel nano-delivery system for the treatment of MDR tumors has become an important part of nanotechnology. Herein, this review will take those different mechanisms of MDR as the classification standards and systematically summarize the advances in nanotechnology targeting different mechanisms of MDR in recent years. However, it still needs to be seriously considered that there are still some thorny problems in the application of the nano-delivery system against MDR tumors, including the excessive utilization of carrier materials, low drug-loading capacity, relatively narrow targeting mechanism, and so on. It is hoped that through the continuous development of nanotechnology, nano-delivery systems with more universal uses and a simpler preparation process can be obtained, for achieving the goal of defeating cancer MDR and accelerating clinical transformation.

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Multifunctional nanoplatforms co-delivering combinatorial dual-drug for eliminating cancer multidrug resistance

Cited by 31 publications

References 142 publications

Multistage pH-responsive codelivery liposomal platform for synergistic cancer therapy

Multistage pH-responsive codelivery liposomal platform for synergistic cancer therapy

Emerging nanotechnology-based therapeutics to combat multidrug-resistant cancer

Recent Progress of Novel Nanotechnology Challenging the Multidrug Resistance of Cancer

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