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Ultrasmall nanostructured drug based pH-sensitive liposome for effective treatment of drug-resistant tumor.

ABSTRACT: BACKGROUND:Cancer cells always develop ways to resist and evade chemotherapy. To overcome this obstacle, herein, we introduce a programmatic release drug delivery system that imparts avoiding drug efflux and nuclear transport in synchrony via a simple nanostructured drug strategy. RESULTS:The programmatic liposome-based nanostructured drugs (LNSD) contained two modules: doxorubicin (DOX) loaded into tetrahedral DNA (TD,?~?10 nm) to form small nanostructured DOX, and the nanostructured DOX was encapsulated into the pH-sensitive liposomes. In the in vitro and in vivo studies, LNSD shows multiple benefits for drug resistance tumor treatment: (1) not only enhanced the cellular DOX uptake, but also maintained DOX concentration in an optimum level in resistant tumor cells via nanostructure induced anti-efflux effect; (2) small nanostructured DOX efficiently entered into cell nuclear via size depended nuclear-transport for enhanced treatment; (3) improved the pharmacokinetics and biodistribution via reducing DOX leakage during circulation. CONCLUSIONS:The system developed in this study has the potential to provide new therapies for drug-resistant tumor.

SUBMITTER: Li Y

PROVIDER: S-EPMC6884872 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Ultrasmall nanostructured drug based pH-sensitive liposome for effective treatment of drug-resistant tumor.

Li Yanyan Y Zhai Yongxia Y Liu Wei W Zhang Kaixiang K Liu Junjie J Shi Jinjin J Zhang Zhenzhong Z

Journal of nanobiotechnology 20191129 1

<h4>Background</h4>Cancer cells always develop ways to resist and evade chemotherapy. To overcome this obstacle, herein, we introduce a programmatic release drug delivery system that imparts avoiding drug efflux and nuclear transport in synchrony via a simple nanostructured drug strategy.<h4>Results</h4>The programmatic liposome-based nanostructured drugs (LNSD) contained two modules: doxorubicin (DOX) loaded into tetrahedral DNA (TD, ~ 10 nm) to form small nanostructured DOX, and the nanostruct ...[more]

PMID: 31783863

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Project description:PurposeZinc phthalocyanine (ZnPc) has been applied widely in photodynamic therapy (PDT) with high ROS-production capacity and intense absorption in the near-infrared region. However, weak tumor targeting and the aggregation tendency of ZnPc seriously affect the therapeutic effect of PDT. Therefore, overcoming the aggregation of ZnPc and enhancing its antitumor effect were the purpose of this study.MethodsIn this study, we first found that the aggregation behaviors of the photosensitizer ZnPc(TAP)4, ZnPc substituted by tertiary amine groups, were regulated finely by pH and that ZnPc(TAP)4 could be disaggregated gradually as the pH descended. ZnPc(TAP)4 and human serum albumin (HSA) molecules were assembled into nanoparticles (NPs) for tumor targeting. Meanwhile, the chemotherapy drug paclitaxel (Ptx) was loaded into HSA NPs together with ZnPc(TAP)4 for dual antitumor effects. HSA NPs loading both ZnPc(TAP)4 and Ptx (NP-ZnPc[TAP]4-Ptx) were characterized by particle size and in vitro release. Cytotoxicity, subcellular localization, tumor targeting, and anticancer effect in vivo were investigated respectively.ResultsWe found that NP-ZnPc(TAP)4-Ptx had good stability with qualifying particle size. Interestingly, ZnPc(TAP)4 was released from the NPs and the photodynamic activity enhanced in the acidic environment of tumor. In addition, NP-ZnPc(TAP)4-Ptx had prominent cytotoxicity and time-dependent subcellular localization characteristics. Through a three-dimensional animal imaging system, NP-ZnPc(TAP)4-Ptx showed much-enhanced tumor targeting in tumor-bearing mice. Above all, NP-ZnPc(TAP)4-Ptx was demonstrated to have the synergistic anticancer effect of PDT and chemotherapy.ConclusionNP-ZnPc(TAP)4-Ptx had enhanced tumor targeting for the pH-sensitive property of ZnPc(TAP)4 and the transport function of HSA. NP-ZnPc(TAP)4-Ptx possessed a double-anticancer effect through the combination of ZnPc(TAP)4 and Ptx. This drug-delivery system may also be used to carry chemotherapy drugs other than Ptx for improving antitumor effects.

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Ultrasmall nanostructured drug based pH-sensitive liposome for effective treatment of drug-resistant tumor.

Publications

Ultrasmall nanostructured drug based pH-sensitive liposome for effective treatment of drug-resistant tumor.

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