Chemo-photodynamic combined gene therapy and dual-modal cancer imaging achieved by pH-responsive alginate/chitosan multilayer-modified magnetic mesoporous silica nanocomposites.
Multifunctional theranostics have offered some interesting new opportunities for cancer therapy and diagnosis in the last decade. Herein, magnetic mesoporous silica nanoparticles (M-MSNs) were designed and synthesized, then the photosensitizer chlorin e6 (Ce6) and antitumor drug doxorubicin (Dox) were adsorbed onto the M-MSNs. Biocompatible alginate/chitosan polyelectrolyte multilayers (PEM) were assembled on the M-MSNs to achieve a pH-responsive drug delivery system and adsorb P-gp shRNA for reversing the multidrug resistance. The obtained M-MSN(Dox/Ce6)/PEM/P-gp shRNA nanocomposites were characterized using TEM, SEM, X-ray diffraction, BET, FTIR and electrophoresis. The nanocomposites with average diameter of 280 nm exhibited a pH-responsive drug release profile, and more singlet oxygen generation in cancer cells after laser illumination. CCK-8 assay and calcein-AM/PI co-staining showed that the multifunctional nanocomplexes significantly increased cell apoptosis in vitro. With tumor-bearing Balb/c mice employed as the animal model, combined photodynamic therapy and chemotherapy was carried out, also achieving synergistic anti-tumor effects in vivo. The cores of bifunctional Fe3O4-Au nanoparticles in the multifunctional nanocomposites enabled dual-modal MR and CT imaging, which illustrated strong tumor uptake of these nanocomposites after intravenous injection into tumor-bearing mice. This work highlights the great potential of magnetic mesoporous silica nanocomposites as a multifunctional delivery platform, which is promising for imaging-guided cancer combination therapy with high efficacy.
Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, P. R. China. liuyiyao@uestc.edu.cn liuyiyao@hotmail.com.
Hong
H
Yang
Yin
Y
Chen
Zhongyuan
Z
Chen
Yue
Y
Geng
Xiaoxue
X
Xie
Xue
X
Shen
Tingting
T
Li
Shun
S
Li
Chunhui
C
Wu
Yiyao
Y
Liu
D000464:Alginates / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D045744:Cell Line, Tumor; D048271:Chitosan / Q000031:analogs & derivatives*; D002735:Chlorophyllides; D003692:Delayed-Action Preparations / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008279:Magnetic Resonance Imaging / Q000379:methods; D008807:Mice, Inbred BALB C; D053761:Nanocomposites / Q000737:chemistry*; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000628:therapy*; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000627:therapeutic use; D011166:Porphyrins / Q000008:administration & dosage / Q000627:therapeutic use; D012822:Silicon Dioxide / Q000737:chemistry*; D000068936:Theranostic Nanomedicine / Q000379:methods*
D000464:Alginates; D000970:Antineoplastic Agents; D002735:Chlorophyllides; D003692:Delayed-Action Preparations; D006603:Hexuronic Acids; D017319:Photosensitizing Agents; D011166:Porphyrins; C062985:phytochlorin; D012822:Silicon Dioxide; D004317:Doxorubicin; D020723:Glucuronic Acid; D048271:Chitosan