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Cited by 376Photodynamic Therapy Research StudiesNanoplatforms for cancer theranosticsNanoparticle-Based Drug Delivery

Catalase-Integrated Hyaluronic Acid as Nanocarriers for Enhanced Photodynamic Therapy in Solid Tumor

Open access
Phua, Soo Zeng Fiona, Yang, Guangbao, Lim, Wei Qi, Verma, Apoorva, Chen, Hongzhong, Thanabalu, Thirumaran, Zhao, Yanli·2019·ACS Nano
DOI 10.1021/acsnano.9b01087
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Abstract

Photodynamic therapy (PDT) as a treatment method has many advantages such as minimal invasiveness, repeatable dosage, and low systemic toxicity. Issues with conventional PDT agents include the limited availability of endogenous oxygen and difficulty in accumulation at the tumor site, which has hindered the successful treatment of tumors. Herein, we developed catalase-encapsulated hyaluronic-acid-based nanoparticles loaded with adamantane-modified photosensitizer for enhanced PDT of solid tumors. Chlorin e6 (Ce6) as the photosensitizer was modified with adamantane to yield adamantane-modified Ce6 (aCe6). The obtained nanosystem (HA-CAT@aCe6) could target overly expressed CD44 receptors on cancer cells, supplying oxygen by converting endogenous hydrogen peroxide (H 2 O 2 ) to oxygen, and improving PDT efficacy upon light irradiation. HA-CAT@aCe6 nanoparticles showed high colloidal stability and monodispersity in aqueous solution. The uptake and targeting property of HA-CAT@aCe6 were demonstrated by confocal microscopy and flow cytometry in the MDA-MB-231 cell line possessing overly expressed CD44 receptors. The encapsulated catalase was able to decompose the endogenous H 2 O 2 to generate O 2 in situ for relieving hypoxia in cells incubated under hypoxic conditions. Cell viability assays indicated that HA-CAT@aCe6 possessed minimal cytotoxicity in the dark, while presenting high cellular toxicity under 660 nm light irradiation at normoxic conditions. As a result of the catalase capability in relieving hypoxia, HA-CAT@aCe6 also exhibited high cellular cytotoxicity under hypoxic condition. In vivo experiments revealed selective tumor accumulation of HA-CAT@aCe6 in MDA-MB-231 tumor bearing nude mice. Significant tumor regression was observed after intravenous injection of HA-CAT@aCe6 under light irradiation in comparison to the control system without loading catalase. Thus, HA-CAT@aCe6 demonstrated a great potential in overcoming hypoxia for targeted PDT.

AI snapshot

Written from the paper’s full text.

TL;DR

The paper reports HA-CAT@aCe6 nanoparticles that combine CD44-targeting hyaluronic acid, catalase, and adamantane-modified chlorin e6 for photodynamic therapy. The system relieves tumor hypoxia by converting endogenous H₂O₂ to O₂ and improves PDT efficacy in MDA-MB-231 cells and tumor-bearing mice.

Key findings

  • HA-CAT@aCe6 NPs had a hydrodynamic diameter of 233.6 nm and zeta potential of −13.6 mV; aCe6 entrapment efficiency was 80.1%, loading efficiency was 2.0% (w/w), and final aCe6 concentration was 9.7 µM.
  • HA-CAT retained more than 90% catalase activity after 2 h with proteinase K, whereas free catalase activity dropped to near zero within 2 h; however, HA-CAT activity was estimated at 15.3% of free catalase.
  • In MDA-MB-231 cells, HA-CAT@aCe6 showed minimal dark cytotoxicity (>90% viability) and IC₅₀ values of 1.4 µM under normoxia and 0.72 µM under hypoxia, compared with HA@aCe6 IC₅₀ values of 2.2 µM and 4.8 µM, respectively.
  • In vivo, HA-CAT@aCe6 plus light produced the greatest tumor growth inhibition, lowest tumor mass, and most severe necrosis by H&E/TUNEL among five treatment groups, with no major systemic toxicity observed.

Methods

  • HA-CD was conjugated to catalase via EDC/HOBt coupling, and aCe6 was loaded by supramolecular inclusion between adamantane and β-cyclodextrin; the HA-CD:catalase mass ratio of 3:1 was selected for further study.
  • Characterization included TEM, DLS, zeta potential, SDS-PAGE, absorbance, BCA protein assay, Amplex Red catalase assay, Góth method, SOSG singlet oxygen detection, confocal microscopy, and flow cytometry.
  • In vitro studies used CD44⁺ MDA-MB-231 and CD44⁻ MCF-7 cells under normoxia (21% O₂) and hypoxia (1% O₂); in vivo studies used MDA-MB-231 tumor-bearing nude mice, five groups of five mice, intravenous injection, and 660 nm light irradiation (50 mW/cm² for 30 min), with tumor volume monitored for 14 days.

Limitations

  • The paper does not state a dedicated limitations section.
  • Evident from the text: catalase activity in HA-CAT was only 15.3% of free catalase, which may constrain oxygen generation despite retained stability.
  • Evident from the text: efficacy and targeting were tested mainly in MDA-MB-231 breast cancer cells and one MDA-MB-231 tumor model, with no long-term survival or chronic toxicity assessment beyond 14-day tumor growth and organ histology.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1021/acsnano.9b01087

Cites

52 of 52 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 31 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    After conjugation of HA-CD onto catalase to form HA-CAT, a trailing band was observed in SDS-PAGE, resulting from increased molecular weight of HA-CAT.

    “After the conjugation of HA-CD onto catalase to form HA-CAT, a trailing band was observed in the SDS-PAGE lane (lane 3), which was a result of the increased molecular weight of HA-CAT.”
    Quote in the paperSubstantial claim
  • Findingown data

    TEM images show a spherical morphology for both HA-CAT and HA-CAT@aCe6 NPs.

    “Transmission electron microscopy (TEM) images show a spherical morphology for both HA-CAT and HA-CAT@aCe6 NPs (Figure 1a,b).”
    Quote in the paperNot a substantial claim
  • Findingown data

    Presence of characteristic absorbance bands of aCe6 at around 400 nm and 660 nm with aggregation-induced blue shift confirmed successful entrapment of aCe6 in HA-CAT@aCe6 NPs.

    “After the photosensitizer loading, the presence of characteristic absorbance bands of aCe6 at around 400 nm and 660 nm with the aggregation-induced blue shift confirmed the successful entrapment of aCe6 in HA-CAT@aCe6 NPs (Figure 1f).”
    Quote in the paperSubstantial claim
  • Findingown data

    Vertical gel electrophoresis verified successful synthesis of HA-CAT.

    “Vertical gel electrophoresis was used to verify the successful synthesis of HA-CAT (Figure 1e).”
    Quote in the paperSubstantial claim
  • Findingown data

    The mass amount of HA-CD to catalase in HA-CAT was approximately 1.4:1.

    “The mass amount of HA-CD to catalase was approximately 1.4:1 as determined by the subtraction of the catalase mass (measured by the BCA protein assay) from the known dried mass of HA-CAT.”
    Quote in the paperNot a substantial claim
  • May combine two claims. 32
  • Classified as probably not a substantial claim. 7

  • May combine two claims.

    Findingown data

    H2O2 and HA@aCe6 NPs did not have a significant effect on generation of O2 in solution.

    “As shown in Figure 1g, H2O2 and HA@aCe6 NPs (control group without catalase loaded) did not have a significant effect on the generation of O2 in the solution.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    HA-CD:catalase mass ratio of 3:1 was chosen for further studies because the obtained HA-CAT had a reasonable hydrodynamic diameter suitable for tumor accumulation and better retained catalase activity.

    “HA-CD:catalase mass ratio of 3:1 was eventually chosen for further studies, since the obtained HA-CAT has a reasonable hydrodynamic diameter suitable for the accumulation in tumor 48 and better retained activity of catalase (Figure S5 and Table S1).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [48] source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    HA-CAT NPs in water have a hydrodynamic diameter of 224.0 nm and zeta potential of -20.3 mV.

    “HA-CAT NPs in water have a hydrodynamic diameter of 224.0 nm as measured by the dynamic light scattering (DLS) with zeta potential of -20.3 mV”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Free catalase has a diameter of approximately 9.4 nm and zeta potential of -3.4 mV.

    “while free catalase has a diameter of approximately 9.4 nm with zeta potential of -3.4 mV.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    HA-CAT@aCe6 NPs have a hydrodynamic diameter of 233.6 nm and zeta potential of -13.6 mV.

    “HA-CAT@aCe6 NPs are slightly larger with a hydrodynamic diameter of 233.6 nm and zeta potential of -13.6 mV (Figure 1c,d).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    HA-CAT retained more than 90% of its activity after 2 h and remained high after 4 h incubation with proteinase K.

    “In contrast, HA-CAT was still able to retain more than 90% of its activity after 2 h, and the activity remained high even after 4 h.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Cells incubated with HA-CAT@aCe6 NPs showed less green fluorescence signal, indicating HIF-1α expression was reduced and HA-CAT@aCe6 NPs were able to alleviate hypoxia in the cells.

    “Conversely, cells incubated with HA-CAT@aCe6 NPs showed less green fluorescence signal, indicating that the expression in HIF-1α was reduced and HA-CAT@aCe6 NPs were able to alleviate the hypoxia in the cells.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Under hypoxic condition at 1% O2, IC50 of HA@aCe6 increased to 4.8 μM, while IC50 of HA-CAT@aCe6 reduced to 0.72 μM.

    “The IC50 of HA@aCe6 increased to 4.8 µM, while the IC50 of HA-CAT@aCe6 drastically reduced to 0.72 µM under hypoxic condition (Figure S13).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    IC50 was 2.2 μM for HA@aCe6 and 1.4 μM for HA-CAT@aCe6 under normoxic condition.

    “The half maximal inhibitory concentration (IC50) was computed to be 2.2 µM and 1.4 µM for HA@aCe6 and HA-CAT@aCe6 NPs under normoxic condition, respectively.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    HA-CAT@aCe6 or aCe6 with H2O2 under light showed obvious fluorescence increase, indicating comparable 1O2 production capability.

    “Obvious fluorescence increase was measured for HA-CAT@aCe6 or aCe6 with H2O2 when irradiated under light, indicating their comparable 1 O2 production capability.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Free catalase produced O2 at the fastest rate, reaching maximum O2 concentration at 90 s.

    “Comparatively, free catalases produced O2 at the fastest rate, reaching the maximum concentration of O2 at 90 s.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Minimal change in the size of HA-CAT@aCe6 in PBS, cell culture medium, and deionized water over three days indicated good physiological stability.

    “The minimal change in the size of HA-CAT@aCe6 in different solutions (i.e., PBS, cell culture medium, and deionized water) over three days also indicated its good physiological stability (Figure S7).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In MDA-MB-231 tumor-bearing mice treated with PDT, the most severe morphological change and necrosis in tumor slices were observed in group V (HA-CAT@aCe6 NPs with light irradiation), moderate damage in group IV (HA-CAT@aCe6 NPs in the dark), and minimal damage in groups I-III.

    “Based on obtained results (Figure 4e), the most severe morphological change and necrosis from tumor slices were observed in group V, while moderate damages from group IV and minimal damages from groups I-III.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingnone given

    HA-CAT@aCe6 nanoparticles showed high colloidal stability and mono-dispersity in aqueous solution.

    “HA-CAT@aCe6 nanoparticles showed high colloidal stability and mono-dispersity in aqueous solution.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Liver showed weaker fluorescence, and other major organs such as spleen, kidney, heart, and lungs exhibited minimal fluorescence signal.

    “Liver showed weaker fluorescence, and other major organs such as spleen, kidney, heart and lungs exhibited minimal fluorescence signal.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Tumor growth from group V (HA-CAT@aCe6 with light irradiation) was the most inhibited among all groups, indicating the highest anti-tumor efficacy of HA-CAT@aCe6.

    “The tumor growth from group V was the most inhibited one among all groups, indicating the highest anti-tumor efficacy of HA-CAT@aCe6.”
    • Also stated in: § Abstract · plain
      “Significant tumor regression was observed after intravenous injection of HA-CAT@aCe6 under light irradiation in comparison to the control system without loading catalase.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Over time, fluorescence intensity from the aCe6 group decreased, while HA@aCe6 and HA-CAT@aCe6 groups showed enhancement in fluorescence at 24 h.

    “Upon time, the fluorescence intensity from aCe6 group decreased, while HA@aCe6 and HA-CAT@aCe6 groups showed an enhancement in fluorescence at 24 h time point (Figure 3a,b).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Cell viability assays indicated HA-CAT@aCe6 possessed minimal cytotoxicity in the dark, while presenting high cellular toxicity under 660 nm light irradiation at normoxic condition.

    “Cell viability assays indicated that HA-CAT@aCe6 possessed minimal cytotoxicity in the dark, while presenting high cellular toxicity under 660 nm light irradiation at normoxic condition.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The efficacy of PDT is restricted by the penetration depth of low wavelength light in deep-situated tumor, non-specific accumulation of photosensitizers, and the lack of endogenous oxygen in tumor.

    “Despite its extensive use in cancer treatment, the efficacy of PDT is still restricted by the penetration depth of low wavelength light in deep-situated tumor, non-specific accumulation of photosensitizers and the lack of endogenous oxygen in tumor.11”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [11] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Delivery of proteins such as catalase raises concerns of instability in vivo due to physiological proteases, unpredictable protein immunogenicity, and poor in vivo half-life.

    “Delivery of proteins such as catalase raises a few concerns such as its instability in vivo due to the presence of numerous physiological proteases, unpredictable protein immunogenicity, and poor in vivo half-life.27,28”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [27] source

      Not checked in the free run.

    • cites [28] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In situ generation of oxygen using catalase is attractive because it is self-responsive to H2O2 and does not require pre-treatment with O2.

    “Specifically, in situ generation of oxygen using catalase as an enzyme is attractive because it is self-responsive to hydrogen peroxide (H2O2) and does not require pre-treatment with oxygen ( 3 O2).18,19,24”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [18] source

      Not checked in the free run.

    • cites [19] source

      Not checked in the free run.

    • cites [24] source

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    Production of oxygen could ameliorate tumor hypoxia, leading to better PDT efficacy.

    “The production of oxygen could ameliorate tumor hypoxia, leading to better PDT efficacy.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Hypoxic tumor is often resistant to drugs, limiting chemotherapy efficacy.

    “Hypoxic tumor is often resistant to drugs, thus limiting the chemotherapy efficacy.15”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [15] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Many researchers have tried to improve protein stability by encapsulating proteins within inorganic nanoparticles.

    “Many researchers have tried to improve the protein stability by encapsulation them within inorganic nanoparticles (NPs).29,30”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [29] source

      Not checked in the free run.

    • cites [30] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Using organic materials as nanocarriers leads to good biodistribution, easy metabolism, and better biodegradability.

    “In contrast, using organic materials as nanocarriers lead to good biodistribution, easy metabolism and better biodegradablility.[31][32][33][34]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [31][32][33][34]

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    PEGylation is widely used for delivery of proteins/peptides into the human body.

    “PEGylation is widely used in such modification for the delivery of proteins/peptides into the human body.35”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [35] source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Polysaccharides such as dextran and hyaluronic acid as biodegradable polymers have been explored for modifications on proteins.

    “In light of this, polysaccharides such as dextran and hyaluronic acid (HA) as biodegradable polymers 36,39 have been explored for modifications on proteins.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [36] source

      Not checked in the free run.

    • cites [39] source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Polymer modification has advantages including improved stability, solubility, and pharmacokinetics.

    “Numerous advantages of such polymer modification include the improved stability, solubility and pharmacokinetics.36,37”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [36] source

      Not checked in the free run.

    • cites [37] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Many studies have reported using HA as a therapeutic carrier with covalently attached photosensitizers for targeted therapy.

    “Many studies have been reported on using HA as a therapeutic carrier with covalently attached photosensitizers for targeted therapy.[44][45][46]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [44][45][46]

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Supramolecular loading enables separate storage of different components and easy adjustment of the loading ratio between photosensitizer and catalase, which is tunable and predictable.

    “Such supramolecular loading enables separate storage of different components and easy adjustment of the loading ratio between photosensitizer and catalase, which is tunable and predictable.47”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [47] source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Conjugation of catalase with HA-CD polymer did improve its stability in the presence of proteinase K, which is important for tumor targeted delivery in vivo.

    “Therefore, the conjugation of catalase with HA-CD polymer did improve its stability in the presence of proteinase K, which is important for tumor targeted delivery in vivo.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    HA-CAT and HA-CAT@aCe6 did not show obvious differences in O2 production from H2O2, suggesting photosensitizer loading did not affect catalase activity.

    “They did not show obvious differences in the production of O2 from H2O2, suggesting that the photosensitizer loading did not affect the activity of catalase.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Uptake of HA-CAT@aCe6 by CD44+ MDA-MB-231 cells was greater, probably through CD44 receptor-mediated endocytosis.

    “This result indicates that the uptake of HA-CAT@aCe6 by CD44 + MDA-MB-231 cells was greater, probably through CD44 receptormediated endocytosis.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Conjugation of enzymes to polymers is known to improve stability of enzymes due to polymer protection from proteases.

    “The conjugation of enzymes to polymers was known to improve the stability of the enzymes due to the polymer protection from the proteases.37”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [37] source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Production of 1O2 was enhanced in the presence of both catalase and H2O2, which could possibly promote PDT efficacy of HA-CAT@aCe6 NPs in vitro and in vivo.

    “This observation indicates that the production of 1 O2 was enhanced in the presence of both catalase and H2O2, which could possibly promote the PDT efficacy of HA-CAT@aCe6 NPs in vitro and in vivo.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    HA-mediated cellular accumulation coupled with catalase-catalyzed oxygen production from endogenous H2O2 increased the amount of singlet oxygen generated, promoting cell killing efficacy of HA-CAT@aCe6 even under hypoxic condition.

    “HA-mediated cellular accumulation coupled with catalase-catalyzed oxygen production 25 from endogenous H2O2 increased the amount of singlet oxygen generated, promoting the cell killing efficacy of HA-CAT@aCe6 even under hypoxic condition.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [25] Szatrowski T. P., 1991, Cancer Res.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Free Ce6 is not able to accumulate in the tumor site because it is a small molecule and could diffuse in and out of the tumor freely, resulting in being metabolized.

    “Free Ce6 is not able to accumulate in the tumor site, since it is a small molecule and could diffuse in and out of the tumor freely, resulting in being metabolized.50”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [50] source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    HA@aCe6 NPs showed moderate inhibition of tumor growth because accumulated NPs at the tumor site were not able to exhibit enough toxicity to ablate the whole tumor, leading to continual growth.

    “On the other hand, HA@aCe6 NPs showed moderate inhibition of tumor growth because the accumulated NPs at the tumor site were not able to exhibit enough toxicity to ablate the whole tumor.This led to the continual growth of the tumor.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    In the in vivo therapeutic study, 25 tumor-bearing nude mice were randomly divided into five groups (five mice per group).

    “For in vivo therapeutic studies, 25 tumor-bearing nude mice were randomly divided into five groups (five mice per group): I) control group with saline injection only, II) free Ce6 with light irradiation, III) HA@aCe6 NPs with light irradiation, IV) HA-CAT@aCe6 NPs in the dark, and V) HA-CAT@aCe6 NPs with light irradiation.”
    Quote in the paperSubstantial claim
39 of 39

  • The paper relies on this without support.

    HA is biodegradable and biocompatible with high biosafety.

    “HA, a natural polysaccharide composed of alternate units of two sugar monomers i.e., glucuronic acid and Nacetylglucosamine, 40 is biodegradable and biocompatible with high biosafety.”

  • The paper relies on this without support.

    Direct conjugation of photosensitizers onto HA results in difficulties in controlling the amount of photosensitizers delivered and prolonging the storage of light sensitive photosensitizers.

    “On the other hand, such direct conjugation onto the polymer results in the difficulties in controlling the amount of photosensitizers delivered and prolonging the storage of light sensitive photosensitizers.”

  • The paper relies on this without support.

    Inorganic nanoparticle methods often involve complicated synthesis procedures and the inorganic materials used often have issues being metabolized.

    “These methods often involved complicated synthesis procedures and the inorganic materials used often have issues being metabolized.”

  • The paper relies on this without support.

    The intrinsic H2O2 in cancer cells is present at sufficient levels to be catalyzed by catalase in HA-CAT@aCe6 to produce enough O2 to improve PDT efficacy.

    “This outcome could be due to that the intrinsic H2O2 in cancer cells is catalyzed by catalase in HA-CAT@aCe6 to produce more O2 for improving the PDT efficacy.”
4 of 4

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Nanoparticles can generate superoxide radicals while splitting water to produce oxygen, which can promote photodynamic therapy against tumors.

    “Recently, several studies have shown that nanoparticles can also generate superoxide radicals while splitting water to produce oxygen, which can promote photodynamic therapy against tumors. 443 , 444 , 445 , 446”

    From Hypoxia signaling in cancer: Implications for therapeutic interventions (2023) · cites this paper as [445]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Treatment groups III and IV are reversed

    Major

    The results identify group III as HA-CAT@aCe6 in the dark and group IV as HA@aCe6 with light, but the experimental methods assign those treatments to the opposite groups. This makes the reported group-specific tumor outcomes ambiguous.

  • In vivo light-irradiation duration differs

    Major

    The Figure 4 caption specifies 20 minutes of irradiation, but the in vivo therapeutic methods specify 30 minutes for the treated groups.

  • Proteinase K assay identifies different nanoparticle preparations

    Minor

    The Figure 1i caption says the assayed preparation was HA-CAT@aCe6, while the stability-assay methods identify it as HA-CAT. These are distinct preparations in the paper.

  • Tumor collection is stated as both day 4 and day 14

    Minor

    The results say tumors from all treatment groups were excised and weighed on day 14, whereas the methods say mice from each group were sacrificed on day 4 to collect their tumors. Both timelines cannot describe the same animals and tumor measurements.

4 of 4

Cites

Flagged first, then by citations

Research works printed but not linked: 4

  1. Horrobin D. F., 1994, New Approaches to Cancer Treatment: Unsaturated Lipids and Photodynamic Therapy
  2. Beasley N. J., 2002, Cancer Res., 62, 2493
  3. Szatrowski T. P., 1991, Cancer Res., 51, 794
  4. Matsumura Y., 1986, Cancer Res., 46, 6387

Cited by

Sorted by citations

Related

Authors
Phua, S. Z. F., Yang, G., Lim, W. Q., Verma, A., Chen, H., Thanabalu, T., & Zhao, Y.
Affiliations
Nanyang Technological University (SG)
Corresponding author
Zhao, Yanli
ORCID
Venue
ACS Nano
Publisher
American Chemical Society (ACS)
Published
2019-04-09
Volume
13
Issue
4
Pages
4742-4751
ISSN
  • 1936-0851 (ISSN-L)
  • 1936-086X
DOI
10.1021/acsnano.9b01087
OpenAlex
W2937420078
Semantic Scholar
e5cf6d32149402fe313dbf9698251265bd729de4
Cited by
375
References
52
Citations by year
2026: 18 · 2025: 35 · 2024: 37 · 2023: 52 · 2022: 71 · 2021: 77 · 2020: 71 · 2019: 14
FWCI
42.98
Type
journal article
Language
en
Open access
Licence
Locations
  • ACS Nano (publishedVersion)
  • PubMed (publishedVersion)
  • DR-NTU (Nanyang Technological University) (submittedVersion)
Funders
  • Ministry of Education - Singapore (RG114/17, RG5/16, RG11/17)
  • Agency for Science, Technology and Research (A1883c0005)
  • National Research Foundation Singapore (NRF-NRFI2018-03)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
  • Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Keywords
photodynamic therapy, catalase, hyaluronic acid nanoparticles, chlorin e6, CD44 targeting, tumor hypoxia, hydrogen peroxide decomposition, solid tumors, tumor accumulation, MDA-MB-231 breast cancer, tumor regression
MeSH terms
Adamantane, Animals, Breast Neoplasms, Catalase, Chlorophyllides, Female, Humans, Hyaluronic Acid, Mice, Nude, Photochemotherapy, Porphyrins, Photosensitizing Agents, Cell Line, Tumor, Nanocapsules

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