Harnessing photochemical internalization with dual degradable nanoparticles for combinatorial photo-chemotherapy.
Light-controlled drug delivery systems constitute an appealing means to direct and confine drug release spatiotemporally at the site of interest with high specificity. However, the utilization of light-activatable systems is hampered by the lack of suitable drug carriers that respond sharply to visible light stimuli at clinically relevant wavelengths. Here, a new class of self-assembling, photo- and pH-degradable polymers of the polyacetal family is reported, which is combined with photochemical internalization to control the intracellular trafficking and release of anticancer compounds. The polymers are synthesized by simple and scalable chemistries and exhibit remarkably low photolysis rates at tunable wavelengths over a large range of the spectrum up to the visible and near infrared regime. The combinational pH and light mediated degradation facilitates increased therapeutic potency and specificity against model cancer cell lines in vitro. Increased cell death is achieved by the synergistic activity of nanoparticle-loaded anticancer compounds and reactive oxygen species accumulation in the cytosol by simultaneous activation of porphyrin molecules and particle photolysis.
1] Institute of Electronic Structure and Laser (IESL), Foundation for Research and Technology-Hellas (FORTH), PO Box 1527, 71110 Heraklion, Crete, Greece [2] University College London, School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK [3].
George
G
Pasparakis
1] Institute of Electronic Structure and Laser (IESL), Foundation for Research and Technology-Hellas (FORTH), PO Box 1527, 71110 Heraklion, Crete, Greece [2] Institute of Nanoscience and Nanotechnology, NCSR Demokritos, 15310 Aghia Paraskevi, Attiki, Greece [3].
Theodore
T
Manouras
1] Institute of Electronic Structure and Laser (IESL), Foundation for Research and Technology-Hellas (FORTH), PO Box 1527, 71110 Heraklion, Crete, Greece [2] Department of Materials Science and Technology, University of Crete, 71003 Heraklion, Crete, Greece.
Maria
M
Vamvakaki
Institute of Nanoscience and Nanotechnology, NCSR Demokritos, 15310 Aghia Paraskevi, Attiki, Greece.
Panagiotis
P
Argitis
D000080:Acetals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D003593:Cytoplasm; D004337:Drug Carriers; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008027:Light; D053758:Nanoparticles; D055668:Photochemical Processes; D010778:Photochemotherapy / Q000379:methods*; D011108:Polymers
D000080:Acetals; D000970:Antineoplastic Agents; D004337:Drug Carriers; D011108:Polymers; C016067:polyacetal