Restricted accessResearch articleFirst published online 2018-4
Multifunctional mesoporous silica nanoparticles as efficient transporters of doxorubicin and chlorin e6 for chemo-photodynamic combinatorial cancer therapy
A multimodal nanocarrier based on mesoporous silica nanoparticles (MSNs) is developed to co-delivery photosensitizer chlorin e6 (Ce6) and chemotherapeutic agent doxorubicin (Dox) for cancer combination therapy. Ce6 was covalently conjugated with mesoporous silica nanoparticles, which could increase the loading efficiency, and allowed for photodynamic therapy. Doxorubicin was loaded into the pores of mesoporous silica nanoparticles to afford the dual drug delivery system Dox@MSNs-Ce6. These hybrid nanoparticles have an average diameter of about 100 nm and slightly negative charge of about −17 mV. The Dox@MSNs-Ce6 nanoparticles could efficiently enter into cancer cells. The cellular reactive oxygen species level in treated cells increased about 17 times, upon 660 nm light irradiation (10 mW/cm2, 2 min). More importantly, Dox@MSNs-Ce6 exhibited excellent synergistic effect through combining chemotherapy and photodynamic therapy against A549 lung cancer cells. Our work provides an effective strategy for anticancer drug delivery and combination therapy.
HuQSunWWangCet al.
Recent advances of cocktail chemotherapy by combination drug delivery systems. Adv Drug Deliv Rev2016;
98: 19–34.
5.
KempJAShimMSHeoCYet al.
Combo nanomedicine: Co-delivery of multi-modal therapeutics for efficient, targeted, and safe cancer therapy. Adv Drug Deliv Rev2016;
98: 3–18.
6.
MaLKohliM andSmithA.Nanoparticles for combination drug therapy. ACS Nano2013;
7: 9518–9525.
7.
ArgyoCWeissVBräuchleCet al.
Multifunctional mesoporous silica nanoparticles as a universal platform for drug delivery. Chem Mater2014;
26: 435–451.
8.
AznarEOrovalMPascualLet al.
Gated materials for on-command release of guest molecules. Chem Rev2016;
116: 561–718.
TangFLiL andChenD.Mesoporous silica nanoparticles: Synthesis, biocompatibility and drug delivery. Adv Mater Weinheim2012;
24: 1504–1534.
11.
MengHLiongMXiaTet al.
Engineered design of mesoporous silica nanoparticles to deliver doxorubicin and P-glycoprotein siRNA to overcome drug resistance in a cancer cell line. ACS Nano2010;
4: 4539–4550.
12.
MengHMaiWXZhangHet al.
Codelivery of an optimal drug/siRNA combination using mesoporous silica nanoparticles to overcome drug resistance in breast cancer in vitro and in vivo. ACS Nano2013;
7: 994–1005.
13.
MengHWangMLiuHet al.
Use of a lipid-coated mesoporous silica nanoparticle platform for synergistic gemcitabine and paclitaxel delivery to human pancreatic cancer in mice. ACS Nano2015;
9: 3540–3557.
14.
TuJWangTShiWet al.
Multifunctional Znpc-loaded mesoporous silica nanoparticles for enhancement of photodynamic therapy efficacy by endolysosomal escape. Biomaterials2012;
33: 7903–7914.
15.
LiuHYangYWangAet al.
Hyperbranched polyglycerol-doped mesoporous silica nanoparticles for one- and two-photon activated photodynamic therapy. Adv Funct Mater2016;
26: 2561–2570.
16.
ConteCUngaroFMazzagliaAet al. Photodynamic therapy for cancer: Principles, clinical applications, and nanotechnological approaches. In: Alonso M and Garcia-Fuentes M (eds) Nano-Oncologicals, 2014, pp.123–160. Cham: Springer.
17.
DolmansDEJGJFukumuraD andJainRK.Photodynamic therapy for cancer. Nat Rev Cancer2003;
3: 380–387.
18.
ChengS-HLeeC-HYangC-Set al.
Mesoporous silica nanoparticles functionalized with an oxygen-sensing probe for cell photodynamic therapy: Potential cancer theranostics. J Mater Chem2009;
19: 1252–1257.
19.
TuHLinYSLinHYet al.
In vitro studies of functionalized mesoporous silica nanoparticles for photodynamic therapy. Adv Mater2009;
21: 172–177.
20.
ShenJKimH-CSuHet al.
Cyclodextrin and polyethylenimine functionalized mesoporous silica nanoparticles for delivery of siRNA cancer therapeutics. Theranostics2014;
4: 487–497.
21.
ShenJLiuHMuCet al.
Multi-step encapsulation of chemotherapy and gene silencing agents in functionalized mesoporous silica nanoparticles. Nanoscale2017;
9: 5329–5341.
22.
ZhangWShenJSuHet al.
Co-delivery of cisplatin prodrug and chlorine E6 by mesoporous silica nanoparticles for chemo-photodynamic combination therapy to combat drug resistance. ACS Appl Mater Interf2016;
8: 13332–13340.
23.
LuoZCaiKHuYet al.
Mesoporous silica nanoparticles end-capped with collagen: Redox-responsive nanoreservoirs for targeted drug delivery. Angew Chem Int Ed2011;
50: 640–643.
PanLLiuJ andShiJ.Intranuclear photosensitizer delivery and photosensitization for enhanced photodynamic therapy with ultralow irradiance. Adv Funct Mater2014;
24: 7318–7327.
26.
XiaoLGuLHowellSBet al.
Porous silicon nanoparticle photosensitizers for singlet oxygen and their phototoxicity against cancer cells. ACS Nano2011;
5: 3651–3659.
27.
SlowingIIVivero-EscotoJLWuC-Wet al.
Mesoporous silica nanoparticles as controlled release drug delivery and gene transfection carriers. Adv Drug Deliv Rev2008;
60: 1278–1288.
28.
TrewynBGSlowingIIGiriSet al.
Synthesis and functionalization of a mesoporous silica nanoparticle based on the sol–gel process and applications in controlled release. Acc Chem Res2007;
40: 846–853.
29.
AlexisFPridgenEMolnarLKet al.
Factors affecting the clearance and biodistribution of polymeric nanoparticles. Mol Pharm2008;
5: 505–515.
30.
SlowingITrewynBG andLinVSY.Effect of surface functionalization of Mcm-41-type mesoporous silica nanoparticles on the endocytosis by human cancer cells. J Am Chem Soc2006;
128: 14792–14793.
31.
HeCHuYYinLet al.
Effects of particle size and surface charge on cellular uptake and biodistribution of polymeric nanoparticles. Biomaterials2010;
31: 3657–3666.
32.
CelliJPSpringBQRizviIet al.
Imaging and photodynamic therapy: Mechanisms, monitoring, and optimization. Chem Rev2010;
110: 2795–2838.
33.
StolikSDelgadoJAPérezAet al.
Measurement of the penetration depths of red and near infrared light in human “ex vivo” tissues. J Photochem Photobiol B, Biol2000;
57: 90–93.
34.
HuangPLinJWangXet al.
Light-triggered theranostics based on photosensitizer-conjugated carbon dots for smultaneous enhanced-fluorescence imaging and photodynamic therapy. Adv Mater2012;
24: 5104–5110.
35.
RotomskisRValanciunaiteJSkripkaAet al.
Complexes of functionalized quantum dots and chlorine E6 in photodynamic therapy. Lith J Phys2013;
53: 57–68.
36.
PengFSuYWeiXet al.
Silicon-nanowire-based nanocarriers with ultrahigh drug-loading capacity for in vitro and in vivo cancer therapy. Angew Chem Int Ed2013;
52: 1457–1461.
37.
ZhuJLiaoLBianXet al.
Ph-controlled delivery of doxorubicin to cancer cells, based on small mesoporous carbon nanospheres. Small2012;
8: 2715–2720.
38.
LimY-BKimS-MLeeYet al.Cationic hyperbranched poly (amino ester): A novel class of DNA condensing molecule with cationic surface, biodegradable three-dimensional structure, and tertiary amine groups in the interior. J Am Chem Soc2001;
123: 2460–2461.
39.
RobertsonCAEvansDH andAbrahamseH.Photodynamic therapy (Pdt): A short review on cellular mechanisms and cancer research applications for Pdt. J Photochem Photobiol B2009;
96: 1–8.
40.
GongHChengLXiangJet al.
Near‐infrared absorbing polymeric nanoparticles as a versatile drug carrier for cancer combination therapy. Adv Funct Mater2013;
23: 6059–6067.
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