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bibo:doi: 10.1021%2Fnn502807n
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Subject Item: _:vb33481987
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dc:title: results and discussion
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Subject Item: _:vb33481988
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rdf:value: Previous reports indicate that nanoparticle treatment can induce the activation of endolysosomal vesicles after cellular uptake.>>33<<−35 This phenomenon was investigated with a Neutral Red assay (Supporting Information Figure S4), a test used to determine the modulation of endolysosomal activity by measuring the incorporation and retention of the Neutral Red dye within
n2:mentions: n3:22026563

Subject Item: _:vb33481989
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rdf:value: Previous reports indicate that nanoparticle treatment can induce the activation of endolysosomal vesicles after cellular uptake.33−>>35<< This phenomenon was investigated with a Neutral Red assay (Supporting Information Figure S4), a test used to determine the modulation of endolysosomal activity by measuring the incorporation and retention of the Neutral Red dye within
n2:mentions: n3:22697169

Subject Item: _:vb33481990
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rdf:value: with a Neutral Red assay (Supporting Information Figure S4), a test used to determine the modulation of endolysosomal activity by measuring the incorporation and retention of the Neutral Red dye within acidic intracellular vesicles.36,>>37<< MSN and Br–MSN increased Neutral Red uptake at all the tested doses in HUVEC, though the effect was not as pronounced for pure Bromelain treatment.
n2:mentions: n3:18983864

Subject Item: _:vb33481991
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rdf:value: These data suggest that particle internalization in HUVEC increased autophagocytosis, verifying the results of the Neutral Red assay and other reports.>>33<<
n2:mentions: n3:22026563

Subject Item: _:vb33481992
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rdf:value: These data suggest that particle internalization in HUVEC increased autophagocytosis, verifying the results of the Neutral Red assay and other reports.33,>>35<<
n2:mentions: n3:22697169

Subject Item: _:vb33481993
rdf:type: n2:Context
rdf:value: As previously reported in studies performed to evaluate Bromelain activity,>>38<< the proteolytic activity of Br–MSN was affected by decreasing the pH (Figure 4d), increasing the FBS concentration (Figure 4e) in the incubation solution, or decreasing the temperature (Figure 4f).
n2:mentions: n3:14660870

Subject Item: _:vb33481994
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rdf:value: To further analyze the effect of Br–MSN on tumor ECM, we utilized the endothelial capillary network formation assay.>>39<< Matrigel’s ability to induce endothelial cells to form capillary-like structures is well documented.
n2:mentions: n3:11806243

Subject Item: _:vb33481995
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dc:title: conclusion
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Subject Item: _:vb33481996
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rdf:value: Tumor ECM significantly impairs the diffusion of the chemotherapeutics>>41<< impeding the adequate treatment of cancer cells that reside distantly from the blood vessels.
n2:mentions: n3:20417189

Subject Item: _:vb33481997
rdf:type: n2:Context
rdf:value: Tumor ECM significantly impairs the diffusion of the chemotherapeutics41 impeding the adequate treatment of cancer cells that reside distantly from the blood vessels.>>42<< These limitations become even more pronounced when macromolecules8,43,44 or nanoparticles10,12 are used as therapeutics or delivery platforms.
n2:mentions: n3:16361566

Subject Item: _:vb33481998
rdf:type: n2:Context
rdf:value: 42 These limitations become even more pronounced when macromolecules>>8<<,43,44 or nanoparticles10,12 are used as therapeutics or delivery platforms.
n2:mentions: n3:21081901

Subject Item: _:vb33481999
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rdf:value: 42 These limitations become even more pronounced when macromolecules8,>>43<<,44 or nanoparticles10,12 are used as therapeutics or delivery platforms.
n2:mentions: n3:23898462

Subject Item: _:vb33482000
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rdf:value: 42 These limitations become even more pronounced when macromolecules8,43,>>44<< or nanoparticles10,12 are used as therapeutics or delivery platforms.
n2:mentions: n3:16862189

Subject Item: _:vb33482001
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rdf:value: 42 These limitations become even more pronounced when macromolecules8,43,44 or nanoparticles>>10<<,12 are used as therapeutics or delivery platforms.
n2:mentions: n3:20816045

Subject Item: _:vb33482002
rdf:type: n2:Context
rdf:value: 42 These limitations become even more pronounced when macromolecules8,43,44 or nanoparticles10,>>12<< are used as therapeutics or delivery platforms.
n2:mentions: n3:22807037

Subject Item: _:vb33482003
rdf:type: n2:Context
rdf:value: systems designed to deeply penetrate the ECM are sensitive to the action of tumor extracellular metalloproteases that digest the deliverable’s structure, favoring their diffusion in the interstitial space and the release of their payload.>>2<<,45,46 On the other hand, an active approach designed to digest the tumor ECM by imparting carriers with hydrolytic activity could provide significant advantages for the delivery of therapeutics that must be protected during their route to
n2:mentions: n3:21245339

Subject Item: _:vb33482004
rdf:type: n2:Context
rdf:value: designed to deeply penetrate the ECM are sensitive to the action of tumor extracellular metalloproteases that digest the deliverable’s structure, favoring their diffusion in the interstitial space and the release of their payload.2,>>45<<,46 On the other hand, an active approach designed to digest the tumor ECM by imparting carriers with hydrolytic activity could provide significant advantages for the delivery of therapeutics that must be protected during their route to
n2:mentions: n3:16187287

Subject Item: _:vb33482005
rdf:type: n2:Context
rdf:value: designed to deeply penetrate the ECM are sensitive to the action of tumor extracellular metalloproteases that digest the deliverable’s structure, favoring their diffusion in the interstitial space and the release of their payload.2,45,>>46<< On the other hand, an active approach designed to digest the tumor ECM by imparting carriers with hydrolytic activity could provide significant advantages for the delivery of therapeutics that must be protected during their route to the
n2:mentions: n3:16419048

Subject Item: _:vb33482006
rdf:type: n2:Context
rdf:value: Superior diffusion within the tumor parenchyma is also essential for therapeutics designed for thermal ablation>>7<< whose efficiency depends on their homogeneous distribution throughout the tumor volume.
n2:mentions: n3:14597719

Subject Item: _:vb33482007
rdf:type: n2:Context
rdf:value: the surface of a model nanotherapeutic (i.e., MSN) with Bromelain to enhance their diffusion features upon contact with tumor ECM. Bromelain is an enzymatic complex extracted from pineapples, currently used for clinical purposes.17,>>18<<,24−26 The addition of the proteolytic activity onto the surface of MSN was achieved by covalent attachment of the enzymatic complex using well established bioconjugation techniques.
n2:mentions: n3:23304525

Subject Item: _:vb33482008
rdf:type: n2:Context
rdf:value: a greater extent within 1 h than nonproteolytic MSN. Like most hydrolytic enzymes, the activity of Bromelain was hindered by environmental conditions, such as low pH, increased concentration of serum proteins, and decreased temperatures.>>38<< Thus, future endeavors aimed at developing therapeutic strategies based on this approach must implement features to enhance the circulation time and protect Bromelain surface modification during circulation.
n2:mentions: n3:14660870

Subject Item: _:vb33482009
rdf:type: n2:Context
rdf:value: Recent studies have demonstrated the use of controlled proteolytic activity on tumor parenchyma as a successful strategy to increase therapeutic efficacy of macromolecules,>>8<<,9,11 as it favors the efficient diffusion of the treatment within the tumor parenchyma.
n2:mentions: n3:21081901

Subject Item: _:vb33482010
rdf:type: n2:Context
rdf:value: Recent studies have demonstrated the use of controlled proteolytic activity on tumor parenchyma as a successful strategy to increase therapeutic efficacy of macromolecules,8,>>9<<,11 as it favors the efficient diffusion of the treatment within the tumor parenchyma.
n2:mentions: n3:15256445

Subject Item: _:vb33482011
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rdf:value: Recent studies have demonstrated the use of controlled proteolytic activity on tumor parenchyma as a successful strategy to increase therapeutic efficacy of macromolecules,8,9,>>11<< as it favors the efficient diffusion of the treatment within the tumor parenchyma.
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