Synthesis and characterization of NIR-responsive Aurod@pNIPAAm-PEGMA nanogels as vehicles for delivery of photodynamic therapy agents.

0.83 MB·English

by  Shang, Ting

Shangetal.NanoscaleResearchLetters2013,8:4
http://www.nanoscalereslett.com/content/8/1/4
NANO EXPRESS Open Access
Synthesis and characterization of NIR-responsive
Au @pNIPAAm-PEGMA nanogels as vehicles for
rod
delivery of photodynamic therapy agents
Ting Shang1, Cai-ding Wang1, Lei Ren1,2*, Xin-hua Tian3*, Dong-hui Li4, Xue-bin Ke1, Min Chen1 and An-qi Yang1
Abstract
A near-infrared (NIR)-responsive Au @pNIPAAm-PEGMA nanogel was synthesized in two steps, growing a
rod
PEGMA monolayer on the surface of gold nanorods (AuNRs), followed by in situ polymerization and cross-linking
of N-iso-propylacrylamide (NIPAAm) and poly-(ethylene glycol)-methacrylate (PEGMA). The AuNRs and
Au @pNIPAAm-PEGMAnanogelwerecharacterizedbyUV–visspectroscopy,Ramanspectroscopy,Fouriertransform
rod
infraredspectroscopy,andtransmissionelectronmicroscopy,respectively.Thelowercriticalsolutiontemperatureofthe
Au @pNIPAAm-PEGMAnanogelcouldbetunedbychangingthemolarratioofNIPAAm/PEGMA.TheNIR-mediated
rod
drug release behavior of the Au @pNIPAAm-PEGMA nanogel was studied with zinc phthalocyanines (ZnPc ) as a
rod 4
drug model. It was also demonstrated that the loaded ZnPc could keep the capability of generating singlet
4
oxygen, and the in vitro study showed a great photodynamic therapy (PDT) effect on Hela cells. It thus indicated
the potential of this Au @pNIPAAm-PEGMA nanogel for application as a drug carrier in PDT, which might make
rod
contributions to oncotherapy.
Keywords: NIR-responsive, Au @pNIPAAm-PEGMA nanogel, LCST, singlet oxygen, PDT
rod
Background critical solution temperature (LCST; approximately 32°C)
Gold nanoparticles including nanoshells, nanocages, and [12,13].Besides, its LCSTcan be tuned by the addition of
nanorods have drawn increasing attention in photo- a comonomer during polymerization [14,15]. Combining
dynamic therapy (PDT), drug delivery, and diagnostic this temperature-responsive gel and gold nanoparticles
imaging field in recent years [1-5]. Among them, gold together,thetemperature-responsivegelcanbeinduced
nanorods (AuNRs) are of particular interest due to their to collapse by the photothermal conversion of gold
unique optical properties. With the different aspect nanoparticles, which gives rise to much possibility for
ratios and the resulting longitudinal surface plasmon the application of the temperature-responsive gel in
resonance (SPR), AuNRs exhibit an absorption band in drug delivery. The composites of Au@pNIPAAm have
the near-infrared (NIR) region [6], which conduces to been synthesized and studied in many works [16-18].
higher photothermal conversion and also shows signifi- However, the combination mostly through the physical
cant biomedical application in view of the penetration of embedding effect or electrostatic interaction between
NIR lightinto biologicaltissues [7,8]. gold nanoparticles and pNIPAAm may make the
Poly(N-isopropylacrylamide) (pNIPAAm) gel, as one of composites lack long-term stability, especially in the
the mostwidely studied temperature-responsive polymers biologicalenvironment.Ourpreviousworkhasreported
[9-11], undergoes phase transition in water when the the synthesis of a core-shell structured multifunctional
temperature increases or decreases beyond its lower hybridAu@IPN-pNIPAAmnanogelinwhichthehydro-
gel could be chemically grafted onto a single gold
*Correspondence:[email protected];[email protected] nanoparticle[19].
1DepartmentofBiomaterials,ResearchCenterofBiomedicalEngineering,
Herein, we developed a new way to immobilize
CollegeofMaterials,XiamenUniversity,Xiamen361005,China
3NeurosurgicalDepartmentofAffiliatedZhongshanHospital,Xiamen pNIPAAm combined with poly-(ethylene glycol)-
University,Xiamen361004,China methacrylate (PEGMA) on the surface of AuNRs through
Fulllistofauthorinformationisavailableattheendofthearticle
©2013Shangetal.;licenseeSpringer.ThisisanOpenAccessarticledistributedunderthetermsoftheCreativeCommons
AttributionLicense(http://creativecommons.org/licenses/by/2.0),whichpermitsunrestricteduse,distribution,andreproduction
inanymedium,providedtheoriginalworkisproperlycited.
Shangetal.NanoscaleResearchLetters2013,8:4 Page2of8
http://www.nanoscalereslett.com/content/8/1/4
chemical grafting to obtain NIR-responsive Au @ 400 to 1,000 nm. The transmission electron microscopy
rod
pNIPAAm-PEGMA nanogel. ZnPc a photosensitizer, was (TEM) images were obtained from a JEM 2100 micro-
4,
usedasdrugmodeltoinvestigatethedrugloadingandre- scope (JEOL Ltd., Tokyo, Japan) operating at an accel-
leasepropertiesoftheAu @pNIPAAm-PEGMAnanogel. eration voltage of 200 kV. Raman spectra were
rod
The capacity of generating singlet oxygen of ZnPc4 after performed on an UV-1000x instrument (Renishaw,
being loaded in the Au @pNIPAAm-PEGMA nanogel Wotton-under-Edge, UK) (path length = 200 nm) using
rod
wasmeasured,andtheinvitroPDTwasalsostudied.Our a red light-emitting diode laser (λ = 785 nm, 0.5 mW).
current results suggested the potential of Au @ A Fourier transform interferometer (AVATAR360,
rod
pNIPAAm-PEGMAnanogelasacarrierinPDT. Nicolet Instrument Corporation, Madison, WI, USA)
was used to record the absorption spectra of AuNRs
Methods and Au @pNIPAAm-PEGMA nanogels between 400
rod
SynthesisofPEGMA-SHcompound and 4,000 cm−1 at a spectral resolution of 4 cm−1.
0
Concentrations of 1.0 mmol 5,5-dithiobis (2-nitrobenzoic
acid) (DTNB) and 2.0 mmol dicyclohexylcarbodiimide LCSTmeasurementofAu @pNIPAAm-PEGMAnanogel
rod
(DCC)weredissolvedin50mLofdichlormethane,followed In order to investigate the thermal property of the
by the addition of 2.2 mmol 4-dimethylaminopyridine Au @pNIPAAm-PEGMA nanogel, nanogels with dif-
rod
(DMAP) and 2.0 mmol PEGMA. The mixture was de- ferent molar ratios of NIPAAm/PEGMA (1:0, 18:1, 12:1,
gassed with nitrogen and then stirred for 48 h at room 9:1, 6:1, 4.5:1) were synthesized. LCSTs of nanogels were
temperature. After filtration, the filtrate was washed se- measured through turbidimetric measurement. The con-
quentially with water, 5% acetic acid, and water. Then, centration for each Au @pNIPAAm-PEGMA nanogel
rod
the organic phase was dried over magnesium sulfate, in the deionized water was maintained at 1 mg/mL. The
filtered, and evaporated to dryness. The product was lighttransmittancesat600nmwerethenmeasuredbyan
dissolved in 100 mL of water/ethanol (V/V, 4/1) with UV–vis spectrophotometer (TU-1901, Beijing Purkinje
the addition of 2 mL of 1 M sodium borohydride General Instrument Co. Ltd, Beijing, China) equipped
(NaBH ) and stirred for 2 h, and was used without fur- with a temperature-controlled sample holder, and the
4
therpurification. heating rate was set at 0.1°C/min. The LCST was defined
as the initial break point in the resulting transmittance
SynthesisofAu @pNIPAAm-PEGMAnanogel versustemperaturecurves.
rod
AuNRs with a length of 50 nm were synthesized using
the seed-mediated growth method as reported previ- ZnPc loadingandNIR-mediatedZnPc release
4 4
ously [20]. Subsequently, 0.1 mmol PEGMA-SH was Two milligrams of Au @pNIPAAm-PEGMA nanogels
rod
added to 25 mL of the as-prepared AuNRs suspension and 2 mg of ZnPc were dispersed in 10 mL of N,N-
4
(1.6 × 10−6 μmol) and continuously stirred for 5 h at dimethyl formamide (DMF) and stirred for 24 h at room
room temperature. Au @PEGMA was collected by temperature.TheZnPc -loadedAu @pNIPAAm-PEGMA
rod 4 rod
centrifugation at 9,500 rpm for 12 min and then re- nanogels were then collected by centrifugation (9,000 rpm
dispersed in 15 mL of the deionized water, followed by for 12 min). To determine the amount of unloaded ZnPc ,
4
the addition of 1.8 mmol NIPAAm, 0.2 mmol the supernatant was analyzed by an UV–vis spectropho-
PEGMA, 86.69 μmol sodium dodecyl sulfate (SDS), tometer (DUTM800, Beckman Coulter) at 680 nm where
and 12.97 μmol N,N-methylenebisacrylamide (BIS). ZnPc has a maximum absorption. The loading efficiency
4
The mixture was heated to 75°C with stirring and wascalculatedaccordingtothefollowingformula:
maintained in vacuum. After equilibration for 1 h, the
polymerization was initiated by adding 109.6 μmol am- Loadingefficiency ¼Wt(cid:2)W0 (cid:3)100%;
monium persulfate (APS). The reaction was allowed to Wt
proceed for 4 h at 75°C and terminated by opening
the system to air. The resulting Au @pNIPAAm- where W represents the total amount of ZnPc and W
rod t 4 0
PEGMA nanogels were purified by repeated centrifuga- representstheunloadedamountofZnPc .
4
tion (9,000 rpm for 12 min) and subsequently For the NIR-mediated ZnPc release, 5 mL of the
4
lyophilized for further use. ZnPc -loaded Au @pNIPAAm-PEGMA nanogel
4 rod
suspension (1 mg/mL) was placed into dialysis bags
Characterization (molecular weight cutoff, 8 to 14 kDa) and irradiated
The optical properties of AuNRs and Au @pNIPAAm- by an 808-nm laser (0 to 400 mW/cm2) for different
rod
PEGMA nanogels were characterized by an UV–vis times (0 to 60 min). To determine the amount of
spectrophotometer (DUTM800, Beckman Coulter, Brea, ZnPc released, the dialysate was removed and sub-
4
CA, USA) with a scanning speed of 1,200 nm/min from sequently analyzed by an UV–vis spectrophotometer
Shangetal.NanoscaleResearchLetters2013,8:4 Page3of8
http://www.nanoscalereslett.com/content/8/1/4
typical experiment, 0.105 mg of the Au @pNIPAAm-
rod
PEGMA nanogel loaded with 0.0135 μmol ZnPc was
4
dispersedin3mLofDMF,andthen,0.45μmolDMAwas
added. Pure ZnPc (0.0135 μmol) was used as a control.
4
The solutions were then irradiated with a LED lamp (680
nm, 10 mW/cm2) or a NIR laser (808 nm, 400 mW/cm2).
Theabsorptionmeasurementsfollowedbyirradiationwere
carriedoutevery5min.
Light-inducedinvitroPDTeffect
Hela cells were seeded into 24-well cell culture plates
(1 × 105 cells/well) and incubated for 24 h. After being
treated with ZnPc -loaded Au @pNIPAAm-PEGMA
4 rod
nanogels (300 μg/mL) in serum-free medium at 37°C for
22 h, chloroquine (10 mg/mL) was added into every well
Figure1SchematicdescriptionofthesynthesisofPEGMA-SH.
for another 2 h to promote endosomal escape [22].
Then, HelacellswerewashedwithPBSandincubatedina
(DUTM800, Beckman Coulter). The release efficiency nanogel-free medium and treated with an 808-nm laser at
was calculated as follows: 400 mW/cm2 for 15 min and a 680-nm LED lamp at
10mW/cm2for40min.Forcellsurvivaltest,theirradiated
W
Release efficiency ¼ r(cid:3)100%; plateswerereturnedtotheincubator,andcellviabilitywas
W
l colorimetricallymeasured48hlaterwithMTTassay[23].
where W represents the released amount of ZnPc
r 4
and W represents the loaded amount of ZnPc . Results and discussion
l 4
SynthesisofAu @pNIPAAm-PEGMAnanogel
rod
Singletoxygendetection The synthesis of PEGMA-SH was shown in Figure 1.
Thegenerationofsingletoxygen(1O )fromZnPc loaded PEGMA-DTNB compound was firstly gained by the
2 4
intheAu @pNIPAAm-PEGMAnanogelwasdetermined esterification reaction between the terminal hydroxyl
rod
by the transformation of 9,10-dimethylanthracene (DMA) group on the PEGMA and the carboxyl group on the
whichexhibitsamaximumabsorptionat377nm[21].The DTNB with the DCC as medium and DMAP as catalyst
DMA can react irreversibly with 1O to yield an [24,25]. Subsequently, the disulfide bond of PEGMA-
2
endoperoxide. The reaction could be monitored by DTNB was reduced by NaBH to yield the desired
4
recording the decrease in the absorption at 377 nm. In a PEGMA-SHcompound.
Figure2PreparationoftheAu @pNIPAAm-PEGMAnanogel.(1,2)Schematicofthesequenceofstepsinthesynthesisofthehybrid
rod
Au @pNIPAAm-PEGMAnanogels,(3)ZnPc4loadingprocess,and(4)NIR-mediatedZnPc release.
rod 4
Shangetal.NanoscaleResearchLetters2013,8:4 Page4of8
http://www.nanoscalereslett.com/content/8/1/4
Figure3TheUV–visspectraof(a)AuNRsand(b) Figure5TheRamanspectraof(a)AuNRsand(b)
Aurod@pNIPAAm-PEGMAnanogel. Aurod@pNIPAAm-PEGMAnanogel.
ThestrategytopreparetheAu @pNIPAAm-PEGMA shift from 794 to 801 nm occurred (Figure 3b). This red
rod
nanogel involves two steps, growing a PEGMA mono- shiftofSPR andthepeak shapewidening mightbedueto
layer on the surface of a AuNR, followed by in situ achangeforAuNRsinthelocalrefractiveindexproduced
polymerization and cross-linking of NIPAAm and bythepNIPAAm-PEGMAshell(Figure4B)[26].
PEGMA, as depicted in Figure 2. In the first step, the Raman spectra were also used to identify the synthesis
AuNR surface was modified with a PEGMA self- of the Au @pNIPAAm-PEGMA nanogel. The Raman
rod
assembled monolayer through a sulfhydryl-gold inter- spectrumoftheas-preparedAuNRs(Figure5a)exhibited
action. In the second step, PEGMA-modified AuNRs a band at 190 nm which was ascribable to the Au-Br
could be used as a template for in situ formation of bond on the surface of AuNRs [27]. This is because the
hydrogel by polymerization and cross-linking of NIPAM as-preparedAuNRswerestabilizedbythe cationicdeter-
and PEGMA with BIS as crosslinker, APS as initiator, gent cetyltrimethylammonium bromide (CTAB) in the
and SDS as emulsifier. The coating of pNIPAAm- aqueous solution. After being modified with pNIPAAm-
PEGMAonAuNRscanbereflectedinthecorresponding PEGMA (Figure 5b), the Au-Br band disappeared, and a
UV–vis spectra (Figure 3). AuNRs used in this work had bandat320nmwasobserved,whichwasassignedtothe
a length of about 50 nm with an aspect ratio of approxi- Au-S bond [28]. It is thus suggested that PEGMA-SH
mately 3.2 (Figure 4A) which exhibited the maximum of might replace CTAB to form PEGMA-modified AuNRs
the plasmon peak of 794 nm (Figure 3a). After the through the Au-S bond, and then, PEGMA-SH on the
AuNRs were modified with pNIPAAm-PEGMA, a red surface of AuNRs might serve as the template for the
Figure4ThetypicalTEMimagesofAuNRs(A)beforeand(B)aftermodificationwithpNIPAAM-PEGMA,respectively.
Shangetal.NanoscaleResearchLetters2013,8:4 Page5of8
http://www.nanoscalereslett.com/content/8/1/4
Figure6FTIRspectraof(a)Au@PEGMAand(b)Au @pNIPAAm-PEGMAnanogel.
rod
following polymerization and cross-linking of NIPAAm NIPAAm/PEGMA,1:0)exhibitedanLCSTofapproximately
andPEGMA. 32°C, which was consistent withpurepNIPAAm [13]. It
FTIR spectra (Figure 6) were recorded to confirm the is clearly shown in Table 1 that the LCSTs of the
structure of the polymer shell. In the FTIR spectrum of Au @pNIPAAm-PEGMA nanogel could be tuned by
rod
PEGMA-modified AuNRs (Figure 6a), the absorption changing the molar ratio of NIPAAm/PEGMA. Namely,
peaks of PEGMA, including ν(C=O) (1,721 cm−1) and as the molar ratio of NIPAAm/PEGMA decreased, the
ν(C-O-C) (1,105 cm−1), were observed. The spectrum of LCST of the nanogel increased. For example, when the
Au @pNIPAAm-PEGMA nanogels (Figure 6b) exhibited molar ratio of NIPAAm/PEGMA was set at 18:1, the
rod
the characteristic peaks of polymerized NIPAAm at LCST of Au @pNIPAAm-PEGMA nanogels could be
rod
1,650 cm−1 (ν(C=O), amide I) and 1,550 cm−1 (δ(N-H), up to 36°C. The addition of hydrophilic PEGMA
amide II). Hence, the FTIR results could provide evidence increased the hydrophilicity of pNIPAAm due to the
forthesurfacemodificationandpolymerizationonAuNRs. strong interactions between water and hydrophilic
groups on the polymer, which led to an increased LCST
[29]. It is thus expected that this attractive property of
ThermosensitivepropertyofAu @pNIPAAm-PEGMA
rod tunable LCST might make Au @pNIPAAm-PEGMA
rod
nanogel
nanogelsmorepromisingindrugdeliveryapplication.
Figure7andTable1showedtheeffectofthemolarratiosof
NIPAAm/PEGMA on the LCSTs of the Au @pNIPAAm-
rod NIR-mediatedZnPc release
4
PEGMAnanogel.TheAu @pNIPAAm(themolarratioof
rod NIR-mediated release of ZnPc loaded in Aurod@
4
pNIPAAm-PEGMA nanogels was investigated with the
irradiation of a NIR laser (808 nm). When the sample
was irradiated at 200 mW/cm2, the release efficiency
was about 23.5% in the initial 20 min. As the
irradiated time was prolonged, the cumulative release
efficiency was up to 37.4% within 1 h (Figure 8A).
Table1TheLCSTsofAu @pNIPAAm-PEGMAnanogels
rod
withdifferentmolarratiosofNIPAAm/PEGMA
NIPAAm PEGMA NIPAAm/PEGMA LCST(°C)
(mmol) (mmol) (mmol/mmol)
1.8 0 1:0 32
1.8 0.1 18:1 36
1.8 0.15 12:1 38
1.8 0.2 9:1 40
Figure7Thetransmittanceversustemperaturecurvesof
Au @pNIPAAm-PEGMAnanogels.Withdifferentmolarratiosof 1.8 0.3 6:1 42
rod
NIPAAm/PEGMA(1:0,18:1,12:1,9:1,6:1,4.5:1,respectively). 1.8 0.4 4.5:1 44
Shangetal.NanoscaleResearchLetters2013,8:4 Page6of8
http://www.nanoscalereslett.com/content/8/1/4
Figure8NIR-mediatedreleaseofZnPc .(A)Time-and(B)power-dependentofreleaseofZnPc fromAu @pNIPAAm-PEGMA
4 4 rod
nanogels,respectively.
This can be explained by the AuNRs of Au @ carriers, could offer specific drug delivery to the targeted
rod
pNIPAAm-PEGMA nanogels absorbing a certain SPR site,suchasatumorzone.
wavelength light and converting it into heat [30]. The
heat diffused into the polymer shell and caused the Singletoxygendetection
shrinkage of the pNIPAAm-PEGMA nanogels and the In PDT, the photosensitizing drugs should preferentially
release of ZnPc . accumulate in target tissues and subsequently be
4
The effect of laser power density on drug release was activatedbylightwithamatchingwavelengthtogenerate
studied (Figure 8B). Exposure of Au @pNIPAAm- reactive singlet oxygen [32]. The singlet oxygen will
rod
PEGMA nanogels to an 808-nm laser with the power of causethedestructionoftargetcellsbyacomplexcascade
100 mW/ cm2 for 15 min caused 20% of the loaded of chemical, biological, and physiological reactions [33].
ZnPc released. More loaded ZnPc (43.7%) in Au @ The Au @pNIPAAm-PEGMA nanogels served as ZnPc
4 4 rod rod 4
pNIPAAm-PEGMAnanogels could bereleased upon the carrier in PDT; besides the excellent properties of drug
irradiation power of 800 mW/ cm2. This is because loading and release, its effect on the capability of loaded
when irradiated with a low-power NIR laser, small ZnPc togeneratesingletoxygenwasalsoinvestigated.
4
shrinkage of nanogels occurred, whereas a laser at high Photo-induced1O ofZnPc wasexaminedbyachemical
2 4
power might make nanogels shrink considerably and methodbyusingDMA,whichcouldreactwith1O toform
2
rapidly[31],consequently moreZnPc couldbereleased. an endoperoxide. The decrease in amount ofDMAcan be
4
It is thus speculated that the NIR-responsive Au @ recorded by measuring the absorption at 377 nm. As
rod
pNIPAAm-PEGMA nanogel, acting as drug delivery shown in Figure 9, when ZnPc -loaded Au @pNIPAAm-
4 rod
PEGMAnanogelsorpureZnPc wasirradiatedbyan808-
4
Figure9ThegenerationprofilesofsingletoxygenfromZnPc -
4
loadedAu @pNIPAAm-PEGMAnanogels(Au/P).Thenanogels Figure10ThephotodynamictherapyeffectofZnPc -loaded
rod 4
wereirradiatedbyan808-nmlaseranda680-nmLED Au @pNIPAAm-PEGMAnanogelsonHelacellsatdifferent
rod
lamp,respectively. irradiatedconditions.
Shangetal.NanoscaleResearchLetters2013,8:4 Page7of8
http://www.nanoscalereslett.com/content/8/1/4
nm laser, the absorption of DMA remained unchanged Authors’information
withtheincreaseofexposuretimetolight,whereastheab- RL,TXH,andLDHarePh.Ds.andprofessors.ST,WCD,KXB,YAQ,andCMare
M.D.studentsintheDepartmentofBiomaterials,CollegeofMaterials,
sorption of DMA continuously decreased as the ZnPc -
4 XiamenUniversity.
loadedAu @pNIPAAm-PEGMAnanogelsorpureZnPc
rod 4
was irradiated by a 680-nm light. This decrease indicated Acknowledgments
the production of 1O , which can irreversibly react with ThisworkwasfinanciallysupportedbytheNationalBasicResearchProgram
2
ofChina(2010CB732402,2013CB933703)andtheNationalNaturalScience
DMA. Moreover, the generation curve of ZnPc -loaded
4 FoundationofChina(30970733,81171448).
Au @pNIPAAm-PEGMA nanogels was similar with
rod
that of pure ZnPc , demonstrating that the capacity of Authordetails
generating 1O of 4ZnPc was hardly affected after being 1DepartmentofBiomaterials,ResearchCenterofBiomedicalEngineering,
2 4 CollegeofMaterials,XiamenUniversity,Xiamen361005,China.2StateKey
loaded in Aurod@pNIPAAm-PEGMA nanogels. It is LaboratoryforPhysicalChemistryofSolidSurfaces,XiamenUniversity,
thus suggested that the Au @pNIPAAm-PEGMA Xiamen361005,China.3NeurosurgicalDepartmentofAffiliatedZhongshan
rod Hospital,XiamenUniversity,Xiamen361004,China.4CollegeofMedicine,
nanogel might be a promising drug carrier for photo-
XiamenUniversity,Xiamen361005,China.
dynamictherapyinthefuture.
Received:19November2012Accepted:11December2012
Published:2January2013
InvitroPDTstudyonHelacells
The in vitro PDT study, represented in Figure 10, References
showed the percentage of cell viability after treatment of 1. HanG,GhoshP,RotelloVM:Functionalizedgoldnanoparticlesfordrug
delivery.Nanomedicine2007,2:113–123.
Hela cells with the ZnPc -loaded Au @pNIPAAm-
4 rod 2. LalS,ClareSE,HalasNJ:Nanoshell-enabledphotothermalcancertherapy:
PEGMA nanogel (300 μg/mL) at different irradiated impendingclinicalimpact.AccChemRes2008,41:1842–1851.
conditions. Compared with the cells’group with no light 3. TongL,WeiQS,WeiA,ChengJX:Goldnanorodsascontrastagentsfor
biologicalimaging:opticalproperties,surfaceconjugationand
treatment, no significant difference of the cell viability
photothermaleffects.PhotochemPhotobiol2009,85:21–32.
was found in the 808-nm laser-treated group. However, 4. SkrabalakSE,ChenJ,AuL,LuX,LiX,XiaY:Goldnanocagesfor
for the 680-nm light-treated group, the cell viability biomedicalapplications.AdvMater2007,19:3177–3184.
5. NannT:Nanoparticlesinphotodynamictherapy.NanoBiomedEng2011,
decreased to 40%. It is interesting to note that when
3:137–143.
irradiated by the two lights, the cell viability decreased 6. JanaNR,GearheartL,MurphyCJ:Wetchemicalsynthesisofhighaspect
to 10%. This is because the 808-nm laser treatment ratiocylindricalgoldnanorod.JPhysChemB2001,105:4065–4067.
7. LiaoHW,HafnerJH:Goldnanorodbioconjugates.ChemMater2005,
might result in the release of ZnPc from nanogels,
4 17:4636–4641.
which could improve the efficiency of the generation of 8. ChengJS,LiangQQ,ChangHX,ZhuWJ:RedoxapproachesderivedTin
singlet oxygen after the 680-nm irradiation and thus en- (IV)oxidenanoparticles/graphenenanocompositesasthenear-infrared
absorberforselectivehumanprostatecancercellsdestruction.Nano
hancethePDTeffectonHelacells.
BiomedEng2012,4:76–82.
9. RahimiM,WadajkarA,SubramanianK,YousefM,CuiW,HsiehJT,NguyenKT:
Conclusions Invitroevaluationofnovelpolymer-coatedmagneticnanoparticlesfor
controlleddrugdelivery.Nanomedicine2010,6:672–680.
A facile approach to prepare near-infrared-responsive 10. HeJ,ChenJY,WangP,WangPN,GuoJ,YangWL,WangCC,PengQ:Poly
Au @pNIPAAm-PEGMA nanogels was described. The (N-isopropylacrylamide)-coatedthermo-responsivenanoparticlesfor
rod
LCSTsofthese Au @pNIPAAm-PEGMA nanogels could controlleddeliveryofsulfonatedZn-phthalocyanineinChinesehamster
rod ovarycellsinvitroandzebrafishinvivo.Nanotechnology2007,18:5.
betunedbychangingthemolarratioofNIPAAm/PEGMA. 11. FujimotoKL,MaZW,NelsonDM,HashizumeR,GuanJJ,TobitaK,WagnerWR:
ThereleaseofZnPc loadedinAu @pNIPAAm-PEGMA Synthesis,characterizationandtherapeuticefficacyofabiodegradable,
4 rod
nanogels increased with the extension of irradiated time thermoresponsivehydrogeldesignedforapplicationinchronicinfarcted
myocardium.Biomaterials2009,30:4357–4368.
andtheincreaseofthepoweroftheNIRlaser.Theloaded 12. QiaoP,NiuQS,WangZB,CaoDP:Synthesisofthermosensitivemicelles
ZnPc in Au @pNIPAAm-PEGMA nanogels could gen- basedonpoly(N-isopropylacrylamide)andpoly(L-alanine)forcontrolled
4 rod
erate singlet oxygen efficiently. The in vitro study showed releaseofadriamycin.ChemEngJ2010,159:257–263.
13. InoueT,ChenGH,NakamaeK,HoffmanAS:Temperaturesensitivityofa
obvious PDT effect on Hela cells. On these bases, the hydrogelnetworkcontainingdifferentLCSToligomersgraftedtothe
Au @pNIPAAm-PEGMA nanogels might serve as a hydrogelbackbone.PolymerGelsandNetworks1997,5:561–575.
rod
promising drug carrier in PDT. 14. WangZC,XuXD,ChenCS,WangGR,ChengSX,ZhangXZ,ZhuRX:Insitu
formation of thermosensitive P(NIPAAm-co-GMA)/PEI hydrogels.
ReactFunctPolym2009,69:14–19.
Competinginterests 15. KargM,HellwegT:New“smart”poly(NIPAM)microgelsandnanoparticle
Theauthorsdeclarethattheyhavenocompetinginterests. microgelhybrids:propertiesandadvancesincharacterisation.CurrOpin
ColloidIn2009,14:438–450.
Authors’contributions 16. Contreras-Cáceres R, PacificoJ, Pastoriza-Santos I,Perez-Juste J,
RLconceivedthestudy,participatedintheexperimentaldesign,andhelped Fernández-BarberoA,Liz-MarzánLM:Au@pNIPAMthermosensitive
draftthemanuscript.TXHparticipatedinthedesignofthestudyand nanostructures:controlovershellcross-linking,overalldimensions,
performedthestatisticalanalysis.STandWCDcarriedoutthepreparation andcoregrowth.AdvFunctMater2009,19:3070–3076.
experimentsanddraftedthemanuscript.LDH,KXB,YAQ,andCM 17. ChenT,ChangDP,ZhangJM,JordanR,ZauscherS:Manipulatingthe
participatedinthecharacterizationexperiments.Allauthorsreadand motionofgoldaggregatesusingstimulus-responsivepatternedpolymer
approvedthefinalmanuscript. brushesasamotor.AdvFunctMater2012,22:429–434.
Shangetal.NanoscaleResearchLetters2013,8:4 Page8of8
http://www.nanoscalereslett.com/content/8/1/4
18. LiWY,CaiX,KimCH,SunGR,ZhangY,DengR,YangMX,ChenJY,AchilefuS,
WangLV,XiaYN:Goldnanocagescoveredwiththermally-responsive
polymersforcontrolledreleasebyhigh-intensityfocusedultrasound.
Nanoscale2011,3:1724–1730.
19. ZhaoXQ,WangTX,LiuW,WangCD,WangD,ShangT,ShenLH,RenL:
MultifunctionalAu@IPN-pNIPAAmnanogelsforcancercellimaging
andcombinedchemo-photothermaltreatment.JMaterChem2011,
21:7240–7247.
20. SauTK,MurPhyCJ:Roomtemperature,high-yieldsynthesisofmultiple
shapesofgoldnanoparticlesinaqueoussolution.JAmChemSoc2004,
126:8648–8649.
21. TempestiTC,Alvarez MG, DurantiniEN: Synthesis and photodynamic
properties of amphiphilicA B-phthalocyanine derivatives bearing
3
N-heterocyclesas potential cationicphototherapeuticagents.
DyesPigments2011, 91:6–12.
22. DouglasKL,PiccirilloCA,TabrizianM:Cellline-dependentinternalization
pathwaysandintracellulartraffickingdeterminetransfectionefficiency
ofnanoparticlevectors.EurJPharmBiopharm2008,68:676–687.
23. TuJ,WangTX,ShiW,WuGS,TianXH,WangYH,GeDT,RenL:
MultifunctionalZnPc-loadedmesoporoussilicananoparticlesfor
enhancementofphotodynamictherapyefficacybyendolysosomal
escape.Biomaterials2012,33:7903–7914.
24. SiskouIC,RekkaEA,KourounakisAP,ChrysselisMC,TsiakitzisK,KourounakisPN:
Designandstudyofsomenovelibuprofenderivativeswithpotential
nootropicandneuroprotectiveproperties.BioorgMedChemLett2007,
15:951–961.
25. PomroyNC,DeberCM:Solubilizationofhydrophobicpeptidesby
reversiblecysteinePEGylation.BiochemBiophResCo1998,245:618–621.
26. SinghN,LyonLA:AunanoparticletemplatedsynthesisofpNIPAm
nanogels.ChemMater2007,19:719–726.
27. LeedhamTJ,PowellDB,ScottJGV:InfraredandRamanspectraof1,5-
cyclooctadienecomplexesofcopper(І),silver(І),gold(І),andgold(III),and
thenatureofthegoldcompounds.SpectrochimiActaA1973,29:559–565.
28. LevinCS,JaneskoBJ,BardhanR,ScuseriaGE,HartgerinkJD,HalasNJ:
Chain-length-dependentvibrationalresonancesinalkanethiolself-
assembledmonolayersobservedonplasmonicnanoparticlesubstrates.
NanoLett2006,6:2617–2621.
29. FeilH,BaeYH,JanFJ,KimSW:Effectofcomonomerhydrophilicityand
ionizationonthelowercriticalsolutiontemperatureofN-
isopropylacrylamidecopolymers.Macromolecules1993,26:2496–2500.
30. KawanoT,NiidomeY,MoriT,KatayamaY,NiidomeT:PNIPAMgel-coated
goldnanorodsfortargeteddeliveryrespondingtoanear-infraredlaser.
BioconjugateChem2009,20:209–212.
31. PalewskaK,SujkaM,Urasińska-WόjcikB,SworakowskiJ,LipińskiJ,NešpůrekS,
RakušanJ,KaráskováM:Light-inducedeffectsinsulfonatedaluminum
phthalocyanines-potentialphotosensitizersinthephotodynamictherapy
spectroscopicandkineticstudy.JPhotochPhotobioA2008,197:1–12.
32. LopezRF,LangeN,GuyR,BentleyMV:Photodynamictherapyofskin
cancer:controlleddrugdeliveryof5-ALAanditsesters.AdvDrugDeliv
Rev2004,56:77–94.
33. CerńyJR,KaráskováM,SanJR,NešpůrekS:Reactiveoxygenspecies
producedbyirradiationofsomephthalocyaninederivatives.
JPhotochemPhotobiolA2010,210:82–88.
doi:10.1186/1556-276X-8-4
Citethisarticleas:Shangetal.:SynthesisandcharacterizationofNIR-
responsiveAu @pNIPAAm-PEGMAnanogelsasvehiclesfordeliveryof
rod
photodynamictherapyagents.NanoscaleResearchLetters20138:4.
Submit your manuscript to a
journal and benefi t from:
7 Convenient online submission
7 Rigorous peer review
7 Immediate publication on acceptance
7 Open access: articles freely available online
7 High visibility within the fi eld
7 Retaining the copyright to your article
Submit your next manuscript at 7 springeropen.com