Abstract：
BACKGROUND:The development of nanocarriers is an important approach to increase the bioavailability of hydrophilic drugs in target cells. In this work, we evaluated the anti-tumorigenic mechanisms and efficacy of NanoALA, a novel nanoformulation of aminolevulic acid (ALA) based on poly(lactide-co-glycolide) (PLGA) nanocapsules designed for anticancer photodynamic therapy (PDT). METHODS:For this purpose, physicochemical characterization, prodrug incorporation kinetics, biocompatibility and photocytotoxicity tests, analysis of the cell death type and mitochondrial function, measurement of the intracellular reactive oxygen species production and DNA fragmentation were performed in murine mammary carcinoma (4T1) cells. RESULTS:NanoALA formulation, stable over a period of 90days following synthesis, presented hydrodynamic diameter of 220±8.7nm, zeta potential of -30.6mV and low value of polydispersity index (0.28). The biological assays indicated that the nanostructured product promotes greater ALA uptake by 4T1 cells and consequently more cytotoxicity in the PDT process. For the first time in the scientific literature, there is a therapeutic efficacy report of approximately 80%, after only 1h of incubation with 100μgmL-1 prodrug (0.6mM ALA equivalent). The mitochondria are probably the initial target of treatment, culminating in energy metabolism disorders and cell death by apoptosis. CONCLUSIONS:NanoALA emerges as a promising strategy for anticancer PDT. Besides being effective against a highly aggressive tumor cell line, the treatment may be economically advantageous because it allows a reduction in the dose and frequency of application compared to free ALA.
journal_name
Photodiagnosis Photodyn Therjournal_title
Photodiagnosis and photodynamic therapyauthors
de Andrade LR,Primo FL,da Silva JR,Tedesco AC,Lacava ZGMdoi
10.1016/j.pdpdt.2017.08.011subject
Has Abstractpub_date
2017-12-01 00:00:00pages
62-70eissn
1572-1000issn
1873-1597pii
S1572-1000(17)30314-9journal_volume
20pub_type
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journal_title：Photodiagnosis and photodynamic therapy
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journal_title：Photodiagnosis and photodynamic therapy
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journal_title：Photodiagnosis and photodynamic therapy
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journal_title：Photodiagnosis and photodynamic therapy
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journal_title：Photodiagnosis and photodynamic therapy
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journal_title：Photodiagnosis and photodynamic therapy
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journal_title：Photodiagnosis and photodynamic therapy
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journal_title：Photodiagnosis and photodynamic therapy
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journal_title：Photodiagnosis and photodynamic therapy
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journal_title：Photodiagnosis and photodynamic therapy
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journal_title：Photodiagnosis and photodynamic therapy
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journal_title：Photodiagnosis and photodynamic therapy
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journal_title：Photodiagnosis and photodynamic therapy
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journal_title：Photodiagnosis and photodynamic therapy
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journal_title：Photodiagnosis and photodynamic therapy
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journal_title：Photodiagnosis and photodynamic therapy
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journal_title：Photodiagnosis and photodynamic therapy
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journal_title：Photodiagnosis and photodynamic therapy
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journal_title：Photodiagnosis and photodynamic therapy
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doi：10.1016/j.pdpdt.2019.101635
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