Photoresponsive biomaterials for targeted drug delivery and 4D cell culture

Biological signalling is regulated through a complex and tightly choreographed interplay between cells and their extracellular matrix. The spatiotemporal control of these interactions is essential for tissue function, and disruptions to this dialogue often result in aberrant cell fate and disease. When disturbances are well understood, correct biological function can be restored through the precise introduction of therapeutics. Moreover, model systems with modifiable physiochemical properties are needed to probe the effects of therapeutic molecules and to investigate cell–matrix interactions. Photoresponsive biomaterials benefit from spatiotemporal tunability, which allows for site-specific therapeutic delivery in vivo and 4D modulation of synthetic cell culture platforms to mimic the dynamic heterogeneity of the human body in vitro. In this Review, we discuss how light can be exploited to modify different biomaterials in the context of photomediated drug delivery and phototunable cell culture platforms. We survey various photochemistries for their applicability in vitro and in vivo and for the biochemical and biophysical modification of materials. Finally, we highlight emerging tools and provide an outlook for the field of photoresponsive biomaterials. Light can initiate chemistries with high spatial and temporal control. In this Review, photoresponsive biomaterials developed for controlled drug delivery and complex tissue engineering are investigated with a focus on photochemistries that provide dynamic precision.

[1]  Jennifer L West,et al.  Micropatterning of poly(ethylene glycol) diacrylate hydrogels with biomolecules to regulate and guide endothelial morphogenesis. , 2009, Tissue engineering. Part A.

[2]  Garry E Gold,et al.  Human Cartilage Repair with a Photoreactive Adhesive-Hydrogel Composite , 2013, Science Translational Medicine.

[3]  H. Breitinger,et al.  Synthesis and characterization of photolabile derivatives of serotonin for chemical kinetic investigations of the serotonin 5-HT(3) receptor. , 2000, Biochemistry.

[4]  J. Allard,et al.  Near-infrared light sensitive polypeptide block copolymer micelles for drug delivery , 2012 .

[5]  L. Suggs,et al.  Dynamic phototuning of 3D hydrogel stiffness , 2015, Proceedings of the National Academy of Sciences.

[6]  Jun Chen,et al.  Nano-Carbon Electrodes for Thermal Energy Harvesting. , 2015, Journal of nanoscience and nanotechnology.

[7]  Peng Shi,et al.  Remote modulation of neural activities via near-infrared triggered release of biomolecules. , 2015, Biomaterials.

[8]  C. Holmes Model Studies for New o-Nitrobenzyl Photolabile Linkers: Substituent Effects on the Rates of Photochemical Cleavage. , 1997, The Journal of organic chemistry.

[9]  Wesley R. Legant,et al.  Degradation-mediated cellular traction directs stem cell fate in covalently crosslinked three-dimensional hydrogels , 2013, Nature materials.

[10]  Robert Langer,et al.  Repeatable and adjustable on-demand sciatic nerve block with phototriggerable liposomes , 2015, Proceedings of the National Academy of Sciences.

[11]  Thommey P. Thomas,et al.  Light-controlled release of caged doxorubicin from folate receptor-targeting PAMAM dendrimer nanoconjugate. , 2010, Chemical communications.

[12]  Krzysztof Palczewski,et al.  Chemistry and Biology of Vision* , 2011, The Journal of Biological Chemistry.

[13]  M. Yazawa,et al.  A photoactivatable Cre-loxP recombination system for optogenetic genome engineering. , 2016, Nature chemical biology.

[14]  Mathieu L. Viger,et al.  Efficient red light photo-uncaging of active molecules in water upon assembly into nanoparticles , 2015, Chemical science.

[15]  M. Tamura,et al.  Optical cell separation from three-dimensional environment in photodegradable hydrogels for pure culture techniques , 2014, Scientific Reports.

[16]  Heather N. Hayenga,et al.  PEGDA hydrogels with patterned elasticity: Novel tools for the study of cell response to substrate rigidity , 2010, Biotechnology and bioengineering.

[17]  Kristi S. Anseth,et al.  Mechanical memory and dosing influence stem cell fate , 2014, Nature materials.

[18]  Molly S. Shoichet,et al.  Three-dimensional spatial patterning of proteins in hydrogels. , 2011, Biomacromolecules.

[19]  Yun Chen,et al.  Copolymers derived from 7-acryloyloxy-4-methylcoumarin and acrylates: 2. Reversible photocrosslinking and photocleavage , 1996 .

[20]  Jinbo Li,et al.  Chemistry and biological applications of photo-labile organic molecules. , 2010, Chemical Society reviews.

[21]  Ali Khademhosseini,et al.  Facile One‐Step Micropatterning Using Photodegradable Gelatin Hydrogels for Improved Cardiomyocyte Organization and Alignment , 2015 .

[22]  K. Landfester,et al.  Dual Stimuli-Responsive Poly(2-hydroxyethyl methacrylate-co-methacrylic acid) Microgels Based on Photo-Cleavable Cross-Linkers: pH-Dependent Swelling and Light-Induced Degradation , 2011 .

[23]  T. Tan,et al.  Photo-Modulated Therapeutic Protein Release from a Hydrogel Depot Using Visible Light. , 2017, Angewandte Chemie.

[24]  V. A. Huu,et al.  Light-responsive nanoparticle depot to control release of a small molecule angiogenesis inhibitor in the posterior segment of the eye. , 2015, Journal of controlled release : official journal of the Controlled Release Society.

[25]  C. DeForest,et al.  Photomediated oxime ligation as a bioorthogonal tool for spatiotemporally-controlled hydrogel formation and modification. , 2017, Journal of materials chemistry. B.

[26]  Joel A. Cohen,et al.  Two-photon degradable supramolecular assemblies of linear-dendritic copolymers. , 2007, Chemical communications.

[27]  Adah Almutairi,et al.  Photocontrolled release using one-photon absorption of visible or NIR light. , 2015, Journal of controlled release : official journal of the Controlled Release Society.

[28]  Ying Zheng,et al.  Multicellular Vascularized Engineered Tissues through User‐Programmable Biomaterial Photodegradation , 2017, Advanced materials.

[29]  Yu-Li Wang,et al.  A photo-modulatable material for probing cellular responses to substrate rigidity. , 2009, Soft matter.

[30]  April M. Kloxin,et al.  Design of thiol–ene photoclick hydrogels using facile techniques for cell culture applications , 2014, Biomaterials science.

[31]  G. Fleming,et al.  Synthetic micelle sensitive to IR light via a two-photon process. , 2005, Journal of the American Chemical Society.

[32]  Fang Liu,et al.  NIR light controlled photorelease of siRNA and its targeted intracellular delivery based on upconversion nanoparticles. , 2013, Nanoscale.

[33]  Carolyn R Bertozzi,et al.  Copper-free click chemistry for the in situ crosslinking of photodegradable star polymers. , 2008, Chemical communications.

[34]  Fangli Zhao,et al.  ortho-Fluoroazobenzenes: visible light switches with very long-Lived Z isomers. , 2014, Chemistry.

[35]  Fuyou Li,et al.  Anticancer drug release from a mesoporous silica based nanophotocage regulated by either a one- or two-photon process. , 2010, Journal of the American Chemical Society.

[36]  Hansoo Park,et al.  Nano "Chocolate Waffle" for near-IR Responsive Drug Releasing System. , 2015, Small.

[37]  Raymond Bonnett,et al.  Photosensitizers of the porphyrin and phthalocyanine series for photodynamic therapy , 1995 .

[38]  Linyong Zhu,et al.  Photocleavable coumarin crosslinkers based polystyrene microgels: phototriggered swelling and release , 2012 .

[39]  Shuai Shao,et al.  Porphyrin–phospholipid liposomes permeabilized by near-infrared light , 2014, Nature Communications.

[40]  D. Kohane,et al.  Efficient Triplet-Triplet Annihilation-Based Upconversion for Nanoparticle Phototargeting. , 2015, Nano letters.

[41]  Kristi S Anseth,et al.  Synthesis of photodegradable hydrogels as dynamically tunable cell culture platforms , 2010, Nature Protocols.

[42]  T. Taguchi,et al.  Photo-Switched Storage and Release of Guest Molecules in the Pore Void of Coumarin-Modified MCM-41 , 2003 .

[43]  Jin-Chul Kim,et al.  7-acetoxycoumarin dimer-incorporated and folate-decorated liposomes: photoresponsive release and in vitro targeting and efficacy. , 2014, Bioconjugate chemistry.

[44]  Roger Y. Tsien,et al.  Photo-mediated gene activation using caged RNA/DNA in zebrafish embryos , 2001, Nature Genetics.

[45]  M. C. Rowland,et al.  Photolithographic patterning of polyethylene glycol hydrogels. , 2006, Biomaterials.

[46]  Mathieu L. Viger,et al.  Highest Efficiency Two-Photon Degradable Copolymer for Remote Controlled Release. , 2013, ACS macro letters.

[47]  Honglai Liu,et al.  Photocontrollable Intermittent Release of Doxorubicin Hydrochloride from Liposomes Embedded by Azobenzene-Contained Glycolipid. , 2017, Langmuir : the ACS journal of surfaces and colloids.

[48]  Barry A Badeau,et al.  Engineered modular biomaterial logic gates for environmentally triggered therapeutic delivery , 2017, Nature chemistry.

[49]  F. Andreopoulos,et al.  Light-induced tailoring of PEG-hydrogel properties. , 1998, Biomaterials.

[50]  Timothy S. Troutman,et al.  Light‐Induced Content Release from Plasmon‐Resonant Liposomes , 2009, Advanced materials.

[51]  R. Leblanc,et al.  A Novel Photoscissile Poly(ethylene glycol)-Based Hydrogel , 2001 .

[52]  N. Murthy,et al.  A synthetic hydrogel for the high-throughput study of cell–ECM interactions , 2015, Nature Communications.

[53]  Mark W. Tibbitt,et al.  In vitro model alveoli from photodegradable microsphere templates. , 2015, Biomaterials science.

[54]  D. Trauner,et al.  A roadmap to success in photopharmacology. , 2015, Accounts of Chemical Research.

[55]  S. Yang,et al.  Visible Light‐Triggered On‐Demand Drug Release from Hybrid Hydrogels and its Application in Transdermal Patches , 2015, Advanced healthcare materials.

[56]  Z. Dang,et al.  Photo, pH, and thermo triple-responsive spiropyran-based copolymer nanoparticles for controlled release. , 2015, Chemical communications.

[57]  Kristi S Anseth,et al.  Controlled two-photon photodegradation of PEG hydrogels to study and manipulate subcellular interactions on soft materials. , 2010, Soft matter.

[58]  byBrooke LaBranche,et al.  Gold nanoparticles in delivery applications ? , 2018 .

[59]  Ashutosh Kumar Singh,et al.  Light-triggered in vivo Activation of Adhesive Peptides Regulates Cell Adhesion, Inflammation and Vascularization of Biomaterials , 2014, Nature materials.

[60]  J. Burdick,et al.  Enhanced release of small molecules from near-infrared light responsive polymer-nanorod composites. , 2011, ACS nano.

[61]  Xi Zhang,et al.  Photocontrolled self-assembly and disassembly of block ionomer complex vesicles: a facile approach toward supramolecular polymer nanocontainers. , 2010, Langmuir : the ACS journal of surfaces and colloids.

[62]  B. Feringa,et al.  Photopharmacology: Beyond Proof of Principle , 2014 .

[63]  Jason A Burdick,et al.  Patterning network structure to spatially control cellular remodeling and stem cell fate within 3-dimensional hydrogels. , 2010, Biomaterials.

[64]  J Fraser Stoddart,et al.  Azobenzene-based light-responsive hydrogel system. , 2009, Langmuir : the ACS journal of surfaces and colloids.

[65]  Ling Gu,et al.  Crystalline magnetic carbon nanoparticle assisted photothermal delivery into cells using CW near-infrared laser beam , 2014, Scientific Reports.

[66]  Ying Luo,et al.  A photolabile hydrogel for guided three-dimensional cell growth and migration , 2004, Nature materials.

[67]  Hong Liu,et al.  Enhanced small interfering RNA delivery into cells by exploiting the additive effect between photo‐sensitive peptides and targeting ligands , 2015, The Journal of pharmacy and pharmacology.

[68]  S. Samanta,et al.  Red-Shifting Azobenzene Photoswitches for in Vivo Use. , 2015, Accounts of chemical research.

[69]  A. De,et al.  Multifunctional gold coated thermo-sensitive liposomes for multimodal imaging and photo-thermal therapy of breast cancer cells. , 2014, Nanoscale.

[70]  Andrés J. García,et al.  Dynamic cell-adhesive microenvironments and their effect on myogenic differentiation. , 2013, Acta biomaterialia.

[71]  C. Palivan,et al.  Photoresponsive polymersomes as smart, triggerable nanocarriers , 2011 .

[72]  Younan Xia,et al.  Stimuli‐Responsive Materials for Controlled Release of Theranostic Agents , 2014, Advanced functional materials.

[73]  Z. Dang,et al.  Nanocomposites of Spiropyran-Functionalized Polymers and Upconversion Nanoparticles for Controlled Release Stimulated by Near-Infrared Light and pH , 2016 .

[74]  Maurice Goeldner,et al.  Phototriggering of cell adhesion by caged cyclic RGD peptides. , 2008, Angewandte Chemie.

[75]  Xiaoling Zhang,et al.  Near-infrared light-responsive core-shell nanogels for targeted drug delivery. , 2011, ACS nano.

[76]  D. Seliktar,et al.  Photo-patterning PEG-based hydrogels for neuronal engineering , 2015 .

[77]  V. Truong,et al.  Photodegradable Gelatin-Based Hydrogels Prepared by Bioorthogonal Click Chemistry for Cell Encapsulation and Release. , 2015, Biomacromolecules.

[78]  Kristi S Anseth,et al.  Photoinitiated polymerization of PEG-diacrylate with lithium phenyl-2,4,6-trimethylbenzoylphosphinate: polymerization rate and cytocompatibility. , 2009, Biomaterials.

[79]  Mary E. Dickinson,et al.  Three‐Dimensional Biomimetic Patterning in Hydrogels to Guide Cellular Organization , 2012, Advanced materials.

[80]  Takuro Niidome,et al.  PEG-modified gold nanorods with a stealth character for in vivo applications. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[81]  Kristi S. Anseth,et al.  Mechanical Properties and Degradation of Chain and Step-Polymerized Photodegradable Hydrogels , 2013, Macromolecules.

[82]  Hui Gao,et al.  Construction of coumarin-based cross-linked micelles with pH responsive hydrazone bond and tumor targeting moiety. , 2016, Journal of materials chemistry. B.

[83]  D. Trauner,et al.  Photoswitchable fatty acids enable optical control of TRPV1 , 2015, Nature Communications.

[84]  John-Christopher Boyer,et al.  Near-infrared light-triggered dissociation of block copolymer micelles using upconverting nanoparticles. , 2011, Journal of the American Chemical Society.

[85]  Jin-Moo Lee,et al.  Photo-activatable Cre recombinase regulates gene expression in vivo , 2015, Scientific Reports.

[86]  Siling Wang,et al.  pH‐ and NIR Light‐Responsive Micelles with Hyperthermia‐Triggered Tumor Penetration and Cytoplasm Drug Release to Reverse Doxorubicin Resistance in Breast Cancer , 2015 .

[87]  N. Gagey-Eilstein,et al.  A blue-absorbing photolabile protecting group for in vivo chromatically orthogonal photoactivation. , 2013, ACS chemical biology.

[88]  M. Reed,et al.  The History of Photodetection and Photodynamic Therapy¶ , 2001, Photochemistry and photobiology.

[89]  Y. Ohmuro-Matsuyama,et al.  Photocontrolled cell adhesion on a surface functionalized with a caged arginine-glycine-aspartate peptide. , 2008, Angewandte Chemie.

[90]  Molly S. Shoichet,et al.  Three-dimensional Chemical Patterning of Transparent Hydrogels , 2008 .

[91]  V. Rotello,et al.  Photocleavable Hydrogels for Light‐Triggered siRNA Release , 2016, Advanced healthcare materials.

[92]  John-Christopher Boyer,et al.  Near infrared light triggered release of biomacromolecules from hydrogels loaded with upconversion nanoparticles. , 2012, Journal of the American Chemical Society.

[93]  H. Dai,et al.  Photothermally enhanced drug delivery by ultrasmall multifunctional FeCo/graphitic shell nanocrystals. , 2011, ACS nano.

[94]  Juan L. Vivero-Escoto,et al.  Photoinduced intracellular controlled release drug delivery in human cells by gold-capped mesoporous silica nanosphere. , 2009, Journal of the American Chemical Society.

[95]  C. Lyons,et al.  Photoswitchable anticancer activity via trans-cis isomerization of a combretastatin A-4 analog. , 2016, Organic & biomolecular chemistry.

[96]  Xue Han,et al.  Light-Triggered Release of Bioactive Molecules from DNA Nanostructures. , 2016, Nano letters.

[97]  Jennifer L West,et al.  Covalently immobilized gradients of bFGF on hydrogel scaffolds for directed cell migration. , 2005, Biomaterials.

[98]  Daniel S. Kohane,et al.  Photoswitchable nanoparticles for in vivo cancer chemotherapy , 2013, Proceedings of the National Academy of Sciences.

[99]  Samuel G. Awuah,et al.  Site-specific and far-red-light-activatable prodrug of combretastatin A-4 using photo-unclick chemistry. , 2013, Journal of medicinal chemistry.

[100]  C. Bettinger,et al.  Photoreconfigurable polymers for biomedical applications: chemistry and macromolecular engineering. , 2014, Biomacromolecules.

[101]  Kristi S. Anseth,et al.  A Versatile Synthetic Extracellular Matrix Mimic via Thiol‐Norbornene Photopolymerization , 2009, Advanced materials.

[102]  Sylvie Maurin,et al.  Coumarinylmethyl caging groups with redshifted absorption. , 2013, Chemistry.

[103]  Yen Wei,et al.  Two-photon-sensitive and sugar-targeted nanocarriers from degradable and dendritic amphiphiles. , 2011, Small.

[104]  Vladimir P Torchilin,et al.  Cell-penetrating peptides: breaking through to the other side. , 2012, Trends in molecular medicine.

[105]  Water-soluble, donor-acceptor biphenyl derivatives in the 2-(o-nitrophenyl)propyl series: highly efficient two-photon uncaging of the neurotransmitter γ-aminobutyric acid at λ = 800 nm. , 2012, Angewandte Chemie.

[106]  A. Russell,et al.  Photoswitchable PEG-CA hydrogels and factors that affect their photosensitivity , 2000 .

[107]  Elizabeth M Topp,et al.  Release from polymeric prodrugs: linkages and their degradation. , 2004, Journal of pharmaceutical sciences.

[108]  C. Yeh,et al.  A tumor-targeted activatable phthalocyanine-tetrapeptide-doxorubicin conjugate for synergistic chemo-photodynamic therapy. , 2017, European journal of medicinal chemistry.

[109]  Akira Harada,et al.  Photoswitchable supramolecular hydrogels formed by cyclodextrins and azobenzene polymers. , 2010, Angewandte Chemie.

[110]  Christopher Deible,et al.  Photoscissable Hydrogel Synthesis via Rapid Photopolymerization of Novel PEG-Based Polymers in the Absence of Photoinitiators⊥ , 1996 .

[111]  Kristi S Anseth,et al.  Three-dimensional biochemical patterning of click-based composite hydrogels via thiolene photopolymerization. , 2008, Biomacromolecules.

[112]  Mikaël M. Martino,et al.  In Situ Cell Manipulation through Enzymatic Hydrogel Photopatterning , 2013 .

[113]  S J Bryant,et al.  Cytocompatibility of UV and visible light photoinitiating systems on cultured NIH/3T3 fibroblasts in vitro , 2000, Journal of biomaterials science. Polymer edition.

[114]  G. Collet,et al.  Short Soluble Coumarin Crosslinkers for Light-Controlled Release of Cells and Proteins from Hydrogels. , 2015, Biomacromolecules.

[115]  I. Weissman,et al.  Synthesis of a photocaged tamoxifen for light-dependent activation of Cre-ER recombinase-driven gene modification. , 2013, Chemical communications.

[116]  Xiaogang Liu,et al.  NIR photoresponsive crosslinked upconverting nanocarriers toward selective intracellular drug release. , 2013, Small.

[117]  R. Langer,et al.  Aptamer photoregulation in vivo , 2014, Proceedings of the National Academy of Sciences.

[118]  Jeremiah A. Johnson,et al.  PEGylated N-Heterocyclic Carbene Anchors Designed To Stabilize Gold Nanoparticles in Biologically Relevant Media. , 2015, Journal of the American Chemical Society.

[119]  Kristi S. Anseth,et al.  Photodegradable Hydrogels for Dynamic Tuning of Physical and Chemical Properties , 2009, Science.

[120]  M. G. Finn,et al.  Synthesis of Photocleavable Linear Macromonomers by ATRP and Star Macromonomers by a Tandem ATRP-Click Reaction: Precursors to Photodegradable Model Networks , 2007 .

[121]  Jennifer L West,et al.  Micron-scale spatially patterned, covalently immobilized vascular endothelial growth factor on hydrogels accelerates endothelial tubulogenesis and increases cellular angiogenic responses. , 2011, Tissue engineering. Part A.

[122]  Kazunori Kataoka,et al.  Light-induced gene transfer from packaged DNA enveloped in a dendrimeric photosensitizer , 2005, Nature materials.

[123]  Adam J Engler,et al.  Intrinsic extracellular matrix properties regulate stem cell differentiation. , 2010, Journal of biomechanics.

[124]  Linyong Zhu,et al.  Highly Discriminating Photorelease of Anticancer Drugs Based on Hypoxia Activatable Phototrigger Conjugated Chitosan Nanoparticles , 2013, Advanced materials.

[125]  J. C. Barnes,et al.  A reversible light-operated nanovalve on mesoporous silica nanoparticles. , 2014, Nanoscale.

[126]  Kristi S. Anseth,et al.  Sequential click reactions for synthesizing and patterning three-dimensional cell microenvironments , 2009 .

[127]  M. Shoichet,et al.  Light-activated immobilization of biomolecules to agarose hydrogels for controlled cellular response. , 2004, Biomacromolecules.

[128]  D. Trauner,et al.  Synthesis of Redshifted Azobenzene Photoswitches by Late-Stage Functionalization. , 2016, Chemistry.

[129]  Jason A Burdick,et al.  Synthesis and orthogonal photopatterning of hyaluronic acid hydrogels with thiol-norbornene chemistry. , 2013, Biomaterials.

[130]  Xianglong Hu,et al.  Photo-Triggered Release of Caged Camptothecin Prodrugs from Dually Responsive Shell Cross-Linked Micelles , 2013 .

[131]  Xiaodong Fan,et al.  Reversible morphology transitions of supramolecular polymer self-assemblies for switch-controlled drug release. , 2015, Chemical Communications.

[132]  J. Kaplan,et al.  Rapid photolytic release of adenosine 5'-triphosphate from a protected analogue: utilization by the Na:K pump of human red blood cell ghosts. , 1978, Biochemistry.

[133]  Christopher N Bowman,et al.  Thiol-ene click chemistry. , 2010, Angewandte Chemie.

[134]  Kristi S Anseth,et al.  Advances in bioactive hydrogels to probe and direct cell fate. , 2012, Annual review of chemical and biomolecular engineering.

[135]  Matthias P Lutolf,et al.  Microscale patterning of hydrogel stiffness through light-triggered uncaging of thiols. , 2014, Biomaterials science.

[136]  Andrea M. Kasko,et al.  Photodegradable Hydrogels to Generate Positive and Negative Features over Multiple Length Scales , 2010 .

[137]  K. Anseth,et al.  Design and characterization of a synthetically accessible, photodegradable hydrogel for user-directed formation of neural networks. , 2014, Biomacromolecules.

[138]  P. Steerenberg,et al.  Targeting pathophysiological rhythms: prednisone chronotherapy shows sustained efficacy in rheumatoid arthritis. , 2010, Annals of the rheumatic diseases.

[139]  Kristi S Anseth,et al.  Tunable Hydrogels for External Manipulation of Cellular Microenvironments through Controlled Photodegradation , 2010, Advanced materials.

[140]  김병수,et al.  Light-Responsive Micelles of Spiropyran Initiated Hyperbranched Polyglycerol for Smart Drug Delivery , 2014 .

[141]  Y. Takaguchi,et al.  A photo-responsive hydrogelator having gluconamides at its peripheral branches. , 2008, Organic & biomolecular chemistry.

[142]  Malar A. Azagarsamy,et al.  Photo‐Click Living Strategy for Controlled, Reversible Exchange of Biochemical Ligands , 2014, Advanced materials.

[143]  P. Pohl,et al.  (Coumarin-4-yl)methyl esters as highly efficient, ultrafast phototriggers for protons and their application to acidifying membrane surfaces. , 2005, Angewandte Chemie.

[144]  Jason A. Burdick,et al.  Sequential crosslinking to control cellular spreading in 3-dimensional hydrogels , 2009 .

[145]  R. Langer,et al.  Photoswitchable Nanoparticles for Triggered Tissue Penetration and Drug Delivery , 2012, Journal of the American Chemical Society.

[146]  H. Butt,et al.  Supramolecular hydrogels constructed by red-light-responsive host-guest interactions for photo-controlled protein release in deep tissue. , 2015, Soft matter.

[147]  Kristi S. Anseth,et al.  Photocontrolled Nanoparticles for On-Demand Release of Proteins , 2012, Biomacromolecules.

[148]  Yanli Zhao,et al.  Photoresponsive real time monitoring silicon quantum dots for regulated delivery of anticancer drugs. , 2016, Journal of materials chemistry. B.

[149]  Verónica San Miguel,et al.  Wavelength-selective caged surfaces: how many functional levels are possible? , 2011, Journal of the American Chemical Society.

[150]  Fuyou Li,et al.  Spatiotemporally Controllable and Cytocompatible Approach Builds 3D Cell Culture Matrix by Photo‐Uncaged‐Thiol Michael Addition Reaction , 2014, Advanced materials.

[151]  R. Givens,et al.  Photoremovable Protecting Groups in Chemistry and Biology: Reaction Mechanisms and Efficacy , 2012, Chemical reviews.

[152]  Kristi S. Anseth,et al.  Photodegradable, Photoadaptable Hydrogels via Radical-Mediated Disulfide Fragmentation Reaction , 2011, Macromolecules.

[153]  T. Furuta,et al.  Coumarin-4-ylmethoxycarbonyls as phototriggers for alcohols and phenols. , 2003, Organic letters.

[154]  Angela M Belcher,et al.  Targeted cytosolic delivery of cell-impermeable compounds by nanoparticle-mediated, light-triggered endosome disruption. , 2010, Nano letters.

[155]  Jennifer L. West,et al.  Three-dimensional micropatterning of bioactive hydrogels via two-photon laser scanning photolithography for guided 3D cell migration. , 2008, Biomaterials.

[156]  R. J. Lee,et al.  Targeted drug delivery via the folate receptor. , 2000, Advanced drug delivery reviews.

[157]  Kristi S. Anseth,et al.  Cytocompatible Click-based Hydrogels with Dynamically-Tunable Properties Through Orthogonal Photoconjugation and Photocleavage Reactions , 2011, Nature chemistry.

[158]  Xingshi Cai,et al.  Preparation and characterization of photo-responsive cell-penetrating peptide-mediated nanostructured lipid carrier , 2014, Journal of drug targeting.

[159]  Kristi S Anseth,et al.  A microwell cell culture platform for the aggregation of pancreatic β-cells. , 2012, Tissue engineering. Part C, Methods.

[160]  V. Popik,et al.  Wolff Rearrangement of 2-diazo-1(2H)-naphthalenone induced by nonresonant two-photon absorption of NIR radiation. , 2004, Journal of the American Chemical Society.

[161]  Christian Franck,et al.  Mechanically Tunable Thin Films of Photosensitive Artificial Proteins: Preparation and Characterization by Nanoindentation , 2008 .

[162]  T. A. Hatton,et al.  Light-regulated supramolecular engineering of polymeric nanocapsules. , 2012, Journal of the American Chemical Society.

[163]  Qiaochun Wang,et al.  Reversible light-controllable intelligent gel based on simple spiropyran-doped with biocompatible lecithin , 2016 .

[164]  Yang Jiao,et al.  Coumarin-containing photo-responsive nanocomposites for NIR light-triggered controlled drug release via a two-photon process. , 2013, Journal of materials chemistry. B.

[165]  Jiaxi Cui,et al.  Light-triggered multifunctionality at surfaces mediated by photolabile protecting groups. , 2013, Macromolecular rapid communications.

[166]  C. S. Ki,et al.  Facile preparation of photodegradable hydrogels by photopolymerization. , 2013, Polymer.

[167]  Kristi S. Anseth,et al.  Coumarin-Based Photodegradable Hydrogel: Design, Synthesis, Gelation, and Degradation Kinetics. , 2014, ACS macro letters.

[168]  Younan Xia,et al.  Targeting gold nanocages to cancer cells for photothermal destruction and drug delivery , 2010, Expert opinion on drug delivery.

[169]  Jennifer L. West,et al.  Three‐Dimensional Biochemical and Biomechanical Patterning of Hydrogels for Guiding Cell Behavior , 2006 .

[170]  Richard A. Evans,et al.  Photo-responsive systems and biomaterials: photochromic polymers, light-triggered self-assembly, surface modification, fluorescence modulation and beyond , 2010 .

[171]  Phototriggered protein syntheses by using (7-diethylaminocoumarin-4-yl)methoxycarbonyl-caged aminoacyl tRNAs , 2016, Nature communications.

[172]  Yingchun Zhu,et al.  Installing dynamic molecular photomechanics in mesopores: a multifunctional controlled-release nanosystem. , 2007, Angewandte Chemie.

[173]  A. Heckel,et al.  Light‐Controlled Tools , 2013 .

[174]  Nongyue He,et al.  Advanced Gold Nanomaterials for Photothermal Therapy of Cancer. , 2016, Journal of nanoscience and nanotechnology.

[175]  Xiaobing Zhang,et al.  Photon-manipulated drug release from a mesoporous nanocontainer controlled by azobenzene-modified nucleic acid. , 2012, ACS nano.

[176]  John H Slater,et al.  Fabrication of 3D Biomimetic Microfluidic Networks in Hydrogels , 2016, Advanced healthcare materials.

[177]  Simon H. Friedman,et al.  Light Control of Insulin Release and Blood Glucose Using an Injectable Photoactivated Depot , 2016, Molecular pharmaceutics.

[178]  Linzhu Zhou,et al.  Multi-responsive polypeptidosome: characterization, morphology transformation, and triggered drug delivery. , 2014, Macromolecular rapid communications.

[179]  April M. Kloxin,et al.  Redirecting Valvular Myofibroblasts into Dormant Fibroblasts through Light-mediated Reduction in Substrate Modulus , 2012, PloS one.

[180]  Zhong Luo,et al.  Polymer-Coated Hollow Mesoporous Silica Nanoparticles for Triple-Responsive Drug Delivery. , 2015, ACS applied materials & interfaces.

[181]  Jianan Liu,et al.  NIR-triggered anticancer drug delivery by upconverting nanoparticles with integrated azobenzene-modified mesoporous silica. , 2013, Angewandte Chemie.

[182]  J. Allard,et al.  A new two-photon-sensitive block copolymer nanocarrier. , 2009, Angewandte Chemie.

[183]  S. Burdette,et al.  Photoisomerization in different classes of azobenzene. , 2012, Chemical Society reviews.

[184]  Giovanny F. Acosta-Vélez,et al.  Hybrid Photopatterned Enzymatic Reaction (HyPER) for in Situ Cell Manipulation , 2014, Chembiochem : a European journal of chemical biology.

[185]  Jianjun Cheng,et al.  Dual Stimuli-Responsive Poly(β-amino ester) Nanoparticles for On-Demand Burst Release. , 2015, Macromolecular bioscience.

[186]  W. Fan,et al.  Photoresponsive Coumarin Polyesters That Exhibit Cross-Linking and Chain Scission Properties , 2013 .

[187]  Kristi S Anseth,et al.  Photoreversible Patterning of Biomolecules within Click-Based Hydrogels , 2011, Angewandte Chemie.

[188]  Wiktor Szymanski,et al.  Photopharmacology: beyond proof of principle. , 2014, Journal of the American Chemical Society.

[189]  Adah Almutairi,et al.  UV and near-IR triggered release from polymeric nanoparticles. , 2010, Journal of the American Chemical Society.

[190]  R. Martínez‐Máñez,et al.  pH- and photo-switched release of guest molecules from mesoporous silica supports. , 2009, Journal of the American Chemical Society.

[191]  A. Kasko,et al.  Photo-selective delivery of model therapeutics from hydrogels. , 2012, ACS macro letters.

[192]  Kristi S Anseth,et al.  In situ elasticity modulation with dynamic substrates to direct cell phenotype. , 2010, Biomaterials.

[193]  Kristi S. Anseth,et al.  Peptide-Functionalized Click Hydrogels with Independently Tunable Mechanics and Chemical Functionality for 3D Cell Culture , 2010, Chemistry of materials : a publication of the American Chemical Society.

[194]  H. Breitinger,et al.  Synthesis and characterization of photolabile derivatives of serotonin for chemical kinetic investigations of the serotonin 5-HT(3) receptor. , 2000, Biochemistry.

[195]  P. Neveu,et al.  o-nitrobenzyl photolabile protecting groups with red-shifted absorption: syntheses and uncaging cross-sections for one- and two-photon excitation. , 2006, Chemistry.

[196]  Gonen Ashkenasy,et al.  Light induced drug delivery into cancer cells. , 2011, Biomaterials.

[197]  Mark W. Tibbitt,et al.  Responsive culture platform to examine the influence of microenvironmental geometry on cell function in 3D. , 2012, Integrative biology : quantitative biosciences from nano to macro.

[198]  J. Zink,et al.  Activation of snap-top capped mesoporous silica nanocontainers using two near-infrared photons. , 2013, Journal of the American Chemical Society.

[199]  J. Burdick,et al.  Hydrogels with differential and patterned mechanics to study stiffness-mediated myofibroblastic differentiation of hepatic stellate cells. , 2014, Journal of the mechanical behavior of biomedical materials.

[200]  Mustapha Mabrouki,et al.  PEG-Based Hydrogel Synthesis via the Photodimerization of Anthracene Groups , 2002 .

[201]  Kristi S Anseth,et al.  Wavelength-controlled photocleavage for the orthogonal and sequential release of multiple proteins. , 2013, Angewandte Chemie.

[202]  C G Morgan,et al.  Active Uptake of Drugs into Photosensitive Liposomes and Rapid Release on UV Photolysis¶ , 2000, Photochemistry and photobiology.

[203]  Surajit Sinha,et al.  Light-controlled gene silencing in zebrafish embryos. , 2007, Nature chemical biology.

[204]  T. Lithgow,et al.  Light-triggered release of ciprofloxacin from an in situ forming click hydrogel for antibacterial wound dressings. , 2015, Journal of materials chemistry. B.

[205]  K. Anseth,et al.  Amplified Photodegradation of Cell‐Laden Hydrogels via an Addition–Fragmentation Chain Transfer Reaction , 2017, Advanced materials.

[206]  Kristi S Anseth,et al.  In Situ Control of Cell Substrate Microtopographies Using Photolabile Hydrogels , 2012, Small.

[207]  Jeffrey I Zink,et al.  Light-activated nanoimpeller-controlled drug release in cancer cells. , 2008, Small.

[208]  Yuta Nihongaki,et al.  Photoactivatable CRISPR-Cas9 for optogenetic genome editing , 2015, Nature Biotechnology.

[209]  Yumay Chen,et al.  4-Hydroxytamoxifen probes for light-dependent spatiotemporal control of Cre-ER mediated reporter gene expression. , 2015, Molecular bioSystems.

[210]  T. Kunitake,et al.  PHOTORESPONSIVE MEMBRANES. REGULATION OF MEMBRANE PROPERTIES BY PHOTOREVERSIBLE cis–trans ISOMERIZATION OF AZOBENZENES , 1980 .

[211]  Malar A. Azagarsamy,et al.  Synthetically Tractable Click Hydrogels for Three-Dimensional Cell Culture Formed Using Tetrazine–Norbornene Chemistry , 2013, Biomacromolecules.

[212]  A. Kasko,et al.  Photodegradable macromers and hydrogels for live cell encapsulation and release. , 2012, Journal of the American Chemical Society.

[213]  Peng Huang,et al.  An aptamer-targeting photoresponsive drug delivery system using "off-on" graphene oxide wrapped mesoporous silica nanoparticles. , 2015, Nanoscale.

[214]  Kristi S. Anseth,et al.  Spatial and temporal control of the alkyne-azide cycloaddition by photoinitiated Cu(II) reduction. , 2011, Nature chemistry.

[215]  S. Sen,et al.  Matrix Elasticity Directs Stem Cell Lineage Specification , 2006, Cell.

[216]  Younan Xia,et al.  Gold nanocages covered by smart polymers for controlled release with near-infrared light , 2009, Nature materials.

[217]  Christopher J Bettinger,et al.  Light-Induced Remodeling of Physically Crosslinked Hydrogels Using Near-IR Wavelengths. , 2014, Journal of materials chemistry. B.

[218]  Shaojun Guo,et al.  Black Phosphorus Nanosheet‐Based Drug Delivery System for Synergistic Photodynamic/Photothermal/Chemotherapy of Cancer , 2017, Advanced materials.

[219]  K. Berg,et al.  Photochemical internalization provides time- and space-controlled endolysosomal escape of therapeutic molecules. , 2010, Journal of controlled release : official journal of the Controlled Release Society.

[220]  Matthias P Lutolf,et al.  In Situ Patterning of Microfluidic Networks in 3D Cell‐Laden Hydrogels , 2016, Advanced materials.

[221]  Samuel G. Awuah,et al.  Visible Light Controlled Release of Anticancer Drug through Double Activation of Prodrug. , 2013, ACS medicinal chemistry letters.

[222]  H Anholt,et al.  Photochemical internalization: a novel technology for delivery of macromolecules into cytosol. , 1999, Cancer research.

[223]  J Moan,et al.  Lysosomes as photochemical targets , 1994, International journal of cancer.

[224]  Qiao Jin,et al.  Biocompatible drug delivery system for photo-triggered controlled release of 5-Fluorouracil. , 2011, Biomacromolecules.

[225]  K. Anseth,et al.  Photoresponsive elastic properties of azobenzene-containing poly(ethylene-glycol)-based hydrogels. , 2015, Biomacromolecules.

[226]  S. Hecht,et al.  o-Fluoroazobenzenes as readily synthesized photoswitches offering nearly quantitative two-way isomerization with visible light. , 2012, Journal of the American Chemical Society.

[227]  Jiaxi Cui,et al.  Light-triggered cross-linking of alginates with caged Ca2+. , 2013, Biomacromolecules.

[228]  J. Ho,et al.  Photocontrolled targeted drug delivery: photocaged biologically active folic acid as a light-responsive tumor-targeting molecule. , 2012, Angewandte Chemie.

[229]  Jeffrey I. Zink,et al.  Photo-Driven Expulsion of Molecules from Mesostructured Silica Nanoparticles , 2007 .

[230]  Cindi M Morshead,et al.  Spatially controlled simultaneous patterning of multiple growth factors in three-dimensional hydrogels. , 2011, Nature materials.

[231]  N. Thakor,et al.  Conjugated polymer and drug co-encapsulated nanoparticles for chemo- and photo-thermal combination therapy with two-photon regulated fast drug release. , 2015, Nanoscale.

[232]  Jason A Burdick,et al.  Nanofibrous Hydrogels with Spatially Patterned Biochemical Signals to Control Cell Behavior , 2015, Advanced materials.

[233]  Keitaro Yoshimoto,et al.  CRISPR–Cas9-based photoactivatable transcription systems to induce neuronal differentiation , 2017, Nature Methods.

[234]  Jennifer L. West,et al.  Three-dimensional photolithographic patterning of multiple bioactive ligands in poly(ethylene glycol) hydrogels , 2010 .

[235]  E M Callaway,et al.  Brominated 7-hydroxycoumarin-4-ylmethyls: photolabile protecting groups with biologically useful cross-sections for two photon photolysis. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[236]  J. Ortega,et al.  Porphyrin-phospholipid liposomes with tunable leakiness. , 2015, Journal of controlled release : official journal of the Controlled Release Society.

[237]  David A Tirrell,et al.  A photoreversible protein-patterning approach for guiding stem cell fate in three-dimensional gels. , 2015, Nature materials.

[238]  Paul A. Janmey,et al.  Mechanisms of mechanical signaling in development and disease , 2011, Journal of Cell Science.

[239]  Qian Liu,et al.  Ultraviolet light-mediated drug delivery: Principles, applications, and challenges. , 2015, Journal of controlled release : official journal of the Controlled Release Society.