Dataset Information

Novel pH-sensitive zinc phthalocyanine assembled with albumin for tumor targeting and treatment.

ABSTRACT:

Purpose

Zinc 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.

Methods

In 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.

Results

We 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.

Conclusion

NP-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.

SUBMITTER: Wang Y

PROVIDER: S-EPMC6251464 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Novel pH-sensitive zinc phthalocyanine assembled with albumin for tumor targeting and treatment.

Wang Ying Y Zheng Ke K Xuan Guangshan G Huang Mingdong M Xue Jinping J

International journal of nanomedicine 20181119

<h4>Purpose</h4>Zinc 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.<h4>Methods</h4>In this study, we first found that the aggregation behaviors of the photos ...[more]

PMID: 30538452

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Project description:In this study, we investigated the potential of a dual-targeted pH-sensitive doxorubicin prodrug-microbubble complex (DPMC) in ultrasound (US)-assisted antitumor therapy. The doxorubicin prodrug (DP) consists of a succinylated-heparin carrier conjugated with doxorubicin (DOX) via hydrazone linkage and decorated with dual targeting ligands, folate and cRGD peptide. Combination of microbubble (MB) and DP, generated via avidin-biotin binding, promoted intracellular accumulation and improved therapeutic efficiency assisted by US cavitation and sonoporation. Aggregates of prepared DP were observed with an inhomogeneous size distribution (average diameters: 149.6±29.8 nm and 1036.2±38.8 nm, PDI: 1.0) while DPMC exhibited a uniform distribution (average diameter: 5.804±2.1 μm), facilitating its usage for drug delivery. Notably, upon US exposure, DPMC was disrupted and aggregated DP dispersed into homogeneous small-sized nanoparticles (average diameter: 128.6±42.3 nm, PDI: 0.21). DPMC could target to angiogenic endothelial cells in tumor region via αvβ3-mediated recognition and subsequently facilitate its specific binding to tumor cells mediated via recognition of folate receptor (FR) after US exposure. In vitro experiments showed higher tumor specificity and killing ability of DPMC with US than free DOX and DP for breast cancer MCF-7 cells. Furthermore, significant accumulation and specificity for tumor tissues of DPMC with US were detected using in vivo fluorescence and ultrasound molecular imaging, indicating its potential to integrate tumor imaging and therapy. In particular, through inducing apoptosis, inhibiting cell proliferation and antagonizing angiogenesis, DPMC with US produced higher tumor inhibition rates than DOX or DPMC without US in MCF-7 xenograft tumor-bearing mice while inducing no obvious body weight loss. Our strategy provides an effective platform for the delivery of large-sized or aggregated particles to tumor sites, thereby extending their therapeutic applications in vivo.

Dataset Information

Novel pH-sensitive zinc phthalocyanine assembled with albumin for tumor targeting and treatment.

Purpose

Methods

Results

Conclusion

Publications

Novel pH-sensitive zinc phthalocyanine assembled with albumin for tumor targeting and treatment.

Similar Datasets

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