Enhanced Photodynamic Efficacy of Zinc Phthalocyanine by Conjugating to Heptalysine

Li, Linsen; Luo, Zhipu; Chen, Zhuo; Chen, Jincan; Zhou, Shanyong; Xu, Peng; Hu, Ping; Wang, Jundong; Chen, Naisheng; Huang, Jinling; Huang, Mingdong

doi:10.1021/bc3002997

Cited by 48 publications

(32 citation statements)

References 28 publications

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“…This is likely due to the relatively low light doses (1.5 or 3 J / cm 2 ) used in the study. We have previously shown that cells can recover from limited redox damage 53.…”

Section: Resultsmentioning

confidence: 99%

“…This is not too surprising. It is often observed that PSs like CPZ can be taken up by cells probably due to the hydrophobic nature of most PSs 53, 54. In the case of HSA:CPZ, it is likely that HSA undergoes a conformational change on tumor cell surfaces and sheds out the CPZ, which is then taken up by tumor cells through non-specific pinocytosis process.…”

Section: Resultsmentioning

confidence: 99%

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A Novel Tumor Targeting Drug Carrier for Optical Imaging and Therapy

Li¹,

Zheng²,

Hu³

et al. 2014

Theranostics

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Human serum albumin (HSA), a naturally abundant protein in blood plasma and tissue fluids, has an extraordinary ligand-binding capacity and is advocated as a drug carrier to facilitate drug delivery. To render it tumor targeting specificity, we generated a recombinant HSA fused with the amino-terminal fragment (ATF) of urokinase, allowing the fusion protein to bind to urokinase receptor (uPAR), which is shown to have a high expression level in many tumors, but not in normal tissues. To test the efficacy of this bifunctional protein (ATF-HSA), a hydrophobic photosensitizer (mono-substituted β-carboxy phthalocyanine zinc, CPZ) was chosen as a cytotoxic agent. A dilution-incubation-purification (DIP) strategy was developed to load the ATF-HSA with this CPZ, forming a 1:1 molecular complex (ATF-HSA:CPZ). We demonstrated that CPZ was indeed embedded inside ATF-HSA at the fatty acid binding site 1 (FA1) of HSA, giving a hydrodynamic radius of 7.5 nm, close to HSA's (6.5 nm). ATF-HSA:CPZ showed high stability and remarkable optical and photophysical properties in aqueous solution. In addition, the molecular complex ATF-HSA:CPZ can bind to recombinant uPAR in vitro and uPAR on tumor cell surfaces, and was efficient in photodynamic killing of tumor cells. The tumor-killing potency of this molecular complex was further demonstrated in a tumor-bearing mouse model at a dose of 0.080 μmol / kg, or 0.050 mg CPZ / kg of mouse body weight. Using fluorescent molecular tomography (FMT), ATF-HSA:CPZ was shown to accumulate specifically in tumors, and importantly, such tumor retention was higher than that of HSA:CPZ. Together, these results indicate that ATF-HSA:CPZ is not only an efficient tumor-specific cytotoxic agent, but also an useful tumor-specific imaging probe. This bifunctional protein ATF-HSA can also be used as a drug carrier for other types of cytotoxic or imaging agents to render them specificity for uPAR-expressing tumors.

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“…This is likely due to the relatively low light doses (1.5 or 3 J / cm 2 ) used in the study. We have previously shown that cells can recover from limited redox damage 53.…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

A Novel Tumor Targeting Drug Carrier for Optical Imaging and Therapy

Li¹,

Zheng²,

Hu³

et al. 2014

Theranostics

Self Cite

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“…In the special case of zinc phthalocyanine (ZnPc), successful conjugation with different nanocarriers has already been demonstrated in many other studies [25,[29][30][31][32][33][34][35][36], and dendritic delivery of PDT agents has been investigated within the last few years to improve upon tumour selectivity, retention and pharmacokinetics [37,38].…”

Section: Introductionmentioning

confidence: 99%

Selective aggregation of PAMAM dendrimer nanocarriers and PAMAM/ZnPc nanodrugs on human atheromatous carotid tissues: a photodynamic therapy for atherosclerosis

Spyropoulos-Antonakakis¹,

Sarantopoulou²,

Trohopoulos³

et al. 2016

Nano Online

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Photodynamic therapy (PDT) involves the action of photons on photosensitive molecules, where atomic oxygen or OH − molecular species are locally released on pathogenic human cells, which are mainly carcinogenic, thus causing cell necrosis. The efficacy of PDT depends on the local nanothermodynamic conditions near the cell/nanodrug system that control both the level of intracellular translocation of nanoparticles in the pathogenic cell and their agglomeration on the cell membrane. Dendrimers are considered one of the most effective and promising drug carriers because of their relatively low toxicity and negligible activation of complementary reactions. Polyamidoamine (PAMAM) dendrite delivery of PDT agents has been investigated in the last few years for tumour selectivity, retention, pharmacokinetics and water solubility. Nevertheless, their use as drug carriers of photosensitizing molecules in PDT for cardiovascular disease, targeting the selective necrosis of macrophage cells responsible for atheromatous plaque growth, has never been investigated. Furthermore, the level of aggregation, translocation and nanodrug delivery efficacy of PAMAM dendrimers or PAMAM/zinc phthalocyanine (ZnPc) conjugates on human atheromatous tissue and endothelial cells is still unknown. In this work, the aggregation of PAMAM zero generation dendrimers (G0) acting as drug delivery carriers, as well as conjugated G0 PAMAM dendrimers with a ZnPc photosensitizer, to symptomatic and asymptomatic human carotid tissues was investigated by using atomic force microscopy (AFM). For the evaluation of the texture characteristics of the AFM images, statistical surface morphological and fractal analytical methodologies and Minkowski functionals were used. All statistical quantities showed that the deposition of nanodrug carriers on healthy tissue has an inverse impact when comparing to the deposition on atheromatous tissue with different aggregation features between G0 and G0/ZnPc nanoparticles and with considerably larger G0/ZnPc aggregations on the atheromatous plaque. The results highlight the importance of using PAMAM dendrimer carriers as a novel and promising PDT platform for atherosclerosis therapies.

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“…Photodynamic therapy (PDT) is a useful method for the treatment of various cancers [1][2][3][4]. PDT involves the use of photochemical reactions mediated through the interaction of photosensitizers (PSs) and appropriate light to generate ROSs and cause irreversible photodamage to tumor cells [5][6][7].…”

mentioning

confidence: 99%

“…Then ZS-ZnPc compound shows extreme photostability upon the irradiation. 1 O 2 is a vitally important species of ROSs for PSs in photodynamic cancer therapy, photooxidation of toxic molecules, and photoproduction of important intermediation for various chemicals because of its high oxidation ability [28]. ADMA was employed as a quencher to reflect the singlet oxygen generation ability of Pcs in aqueous [29,30].…”

mentioning

confidence: 99%