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SCIENCE CHINA Materials, Volume 60, Issue 6: 487-503(2017) https://doi.org/10.1007/s40843-017-9025-3

Hydrogel-based phototherapy for fighting cancer and bacterial infection

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  • ReceivedFeb 24, 2017
  • AcceptedMar 28, 2017
  • PublishedMay 16, 2017

Abstract

Hydrogels constitute a group of polymeric materials which can hold a large amount of water in their three-dimensional networks due to their hydrophilic structures. In the past few years, they have been researched for various biomedical applications, such as drug/cell carriers, tissue engineering, and biosensors. Particularly, the hydrogels used as drug delivery systems have shown distinct advantages in phototherapy. This review presents recent advancements of hydrogel’s use in phototherapeutic applications by focusing on three kinds of phototherapeutic methods including photodynamic therapy (PDT), photothermal therapy (PTT), and phototherapy-containing combination therapy (PCCT). The applications of these therapies in anticancer and antibacterial fields have also been summarized. We hope that this review will inspire researchers to further develop promising materials for phototherapy applications.


Funded by

National Natural Science Foundation of China(21673037)

Graduate Students’ Scientific Research Innovation Project of Jiangsu Province Ordinary University(SJLX16_0054)

Fundamental Research Funds for the Central Universities(2242015R30016)

Six Talents Peak Project in Jiangsu Province(2015-SWYY-003)

and Scientific Research Foundation for the Returned Overseas Chinese Scholars

Ministry of Education(China)


Acknowledgment

This work was supported by the National Natural Science Foundation of China (21673037), Graduate Students’ Scientific Research Innovation Project of Jiangsu Province Ordinary University (SJLX16_0054), Fundamental Research Funds for the Central Universities (2242015R30016), Six Talents Peak Project in Jiangsu Province (2015-SWYY-003), and Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry.


Interest statement

The authors declare that they have no conflict of interest.


Contributions statement

Zhang X, Wu F, Xia L, Chen X, and Chen Z wrote the paper. Wu F, Zhang X, and Chen Z designed the outlines.


Author information

Xiaodong Zhang received his BSc degree in biomedical engineering from Southeast University in 2014. Now, he is a PhD student at Southeast University. His current research interests include the design of hydrogels and fluorescent nanomaterials and their biomedical applications.


Zhan Chen is a professor of chemistry at the University of Michigan, specializing in molecular level studies on surfaces and interfaces using nonlinear optical spectroscopy. Dr. Chen received his BSc, MSc, and PhD. degrees from Peking University, Chinese Academy of Sciences, and UC-Berkeley, respectively. He was a postdoctoral fellow at Lawrence Berkeley National Laboratory.


Fu-Gen Wu is a professor of biomedical engineering in Southeast University. He obtained his BSc and PhD degrees from Tsinghua University in 2006 and 2011, respectively. After a postdoctoral period in the University of Michigan-Ann Arbor, he joined the Faculty of School of Biological Science and Medical Engineering of Southeast University in 2013 and was promoted to be a professor. His main research interests are biomaterials, nanomedicine, and cell surface engineering.


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  • Figure 1

    Synthetic route of the multifunctional polymeric nanomedicine. Reprinted with permission from Ref. [26]. Copyright 2012, American Chemical Society.

  • Figure 2

    (a) Schematic representation of the multi-photo-responsive supramolecular hydrogel and molecular structures of the corresponding compounds; (b) typical photographs of the mixture before and after gelation; (c) photographs of the hydrogel under irradiation of 470 and 650 nm, respectively. Reprinted with permission from Ref. [30]. Copyright 2014, the Royal Society of Chemistry.

  • Figure 3

    The chemical structure of chitosan derivative that contains self-doped PANI side chains and the mechanism of its photothermal cancer treatment. Reprinted with permission from Ref. [46]. Copyright 2015, Elsevier.

  • Figure 4

    (a, b) Locally sustained drug release through a collagen-based hydrogel after intratumoral injection; (c, d) in vivo antitumor activity evaluation using the collagen-based hydrogel. Reprinted with permission from Ref. [50]. Copyright 2016, Wiley Weinheim.

  • Figure 5

    (a) Schematic illustration of the multi-stimuli responsive mussel-inspired hybrid hydrogel as a platform for synergistic anticancer treatment, combining both PTT and multidrug chemotherapy; (b) graph showing the MC3T3-E1 cell viability after exposure to NIPAM-AM-DP and NOPAM-AM-DP/DOX-BTZ for 2, 5, and 7 d; (c) cell viability of CT26 colon cancer cells treated with (A) NIPAM-AM/DP, (B) NIPAM-AM/DP+NIR, (C) NIPAM-AM/DP-BTZ+NIR, (D) NIPAM-AM/DP-DOX+NIR, and (E) NIPAM-AM/DP-BTZ-DOX+NIR. Reprinted with permission from Ref. [66]. Copyright 2016, Macmillan Publishers.

  • Figure 6

    (a) Live imaging of mice with colorectal tumor xenografts implanted with hydrogels that are embedded with drug-Au NRs and siRNA-Au NSs with NIR treatment, either with no tumor resection or after tumor resection. Ex vivo images of tumors and whole body organs (T, tumor; Lv, liver; K, kidneys; S, spleen; H, heart; Lu, lung; Int, intestines) are also depicted; (b,c) tumor burden following treatment as measured by luciferase activity, without tumor resection and after tumor resection; (d) tumor burden of mice treated with gene therapy (siRNA-Au NSs), chemotherapy (drug-Au NRs), phototherapy (Au NRs) or double (chemo + gene, gene + photo, chemo + photo) and triple therapy (gene, chemo and phototherapy combination), as measured by luciferase activity; (e) Kaplan–Meier curves for mice treated with hydrogel scaffolds for gene therapy, chemotherapy, phototherapy or triple therapy (gene therapy, chemotherapy and phototherapy combination); (f) immunohistochemical evaluation of Ki67 for tumors treated with hydrogels alone or following triple therapy; (g) histopathology and biodistribution analyses of tumor tissue from mice treated with triple-therapy combination for several time points (from 6 h to 15 d) (blue, nucleus, DAPI; red, RNAi nanospheres, DY647; green, antibody-drug nanorods, Alexa Fluor 555). Reprinted with permission from Ref. [59]. Copyright 2016, Macmillan Publishers.

  • Table 2   Various phototherapy-involving synergistic treatments for cancer

    Hydrogel

    Drug

    Type of therapy

    Ref.

    Au NRs, spinach extract, PEGDA

    Spinach extract

    PDT

    [48]

    Au NRs

    PTT

    rGO, Au NPs, and amaranth extract

    Amaranth extract

    PDT

    [49]

    rGO, Au NPs

    PTT

    AuCl4 and collagen protein

    TMPyP

    PDT

    [50]

    Au NPs

    PTT

    Alginate

    Hypocrellin B

    PDT

    [51]

    DOX

    Chemotherapy

    Amphiphilic porphyrin and SPPCL-b-PEG

    Porphyrin derivatives

    PDT

    [52]

    DOX

    Chemotherapy

    DNA

    Au NRs

    PTT

    [53]

    DOX

    Chemotherapy

    Gelatin, SWNT, PNIPAM-NH2

    SWNT

    PTT

    [54]

    DOX

    Chemotherapy

    Chitosan and β-glycerophosphate salt

    GO/IONP

    PTT

    [55]

    DOX

    Chemotherapy

    Polypeptide

    Ce6

    PDT

    [56]

    Ce6

    I125

    Brachytherapy

    rGO, Au nanocages, and spinach extract

    Spinach extract

    PDT

    [57]

    rGO, Au nanocages

    PTT

    5-FU

    Chemotherapy

    TiO2@MWCNTs and PEGDA

    TiO2

    PDT

    [58]

    MWCNTs

    PTT

    DOX

    Chemotherapy

    Dextran aldehyde

    Au NRs

    PDT

    [59]

    KRAS (siRNA)

    Gene therapy

    Avastin

    Chemotherapy

  • Table 1   Types of hydrogels and PSs used in photodynamic therapy

    Hydrogel

    PS

    Size/Appearance

    Significance

    Ref

    PAA

    mTHPC

    2–3 nm

    PS-loaded PAA nanogels for cancer therapy

    [23]

    PAA

    MB

    50–60 nm

    PS covalently loaded PAA nanogel for tumor-targeted PDT

    [24]

    30–99 nm

    [25]

    PAA

    HPPH

    44 nm

    PAA-based nanogels for cancer theranostics, including active tumor targeting, fluorescence imaging, and PDT

    [26]

    Chitosan and

    alginate

    TPPS

    ~560 nm

    Antibody-conjugated chitosan/alginate nanogel significantly enhanced the therapeutic effectiveness of entrapped TMP

    [27]

    Molybdenum cluster and

    β-cyclodextrin polymer

    Molybdenum cluster

    ~200 nm

    Inorganic materials as both PSs and hydrogel component

    [28]

    PVA

    TPP or TPyP or TPPS

    Macrogel with a pore size in the range of 80–950 nm

    Water-soluble and -insoluble PSs loaded hydrogel

    [29]

    Poly-β-cyclodextrin and modified dextran, ZnPc, nitric oxide photodonor

    ZnPc, nitric oxide photodonor

    Supramolecular macro hydrogel

    Hydrogel having dual-color fluorescence and dual-modal photodynamic action

    [30]

    PVM/MA and glycerol

    5-ALA

    Hydrogel based microneedles

    Hydrogel-based microneedle arrays for PSs/precursor delivery

    [31]

    Poloxamer 407

    5-ALA

    Thermosetting gel

    Thermosetting gel for PS precursor delivery

    [32]

    PEGDA, PEG, PTA

    ZnPc

    Photopolymerisable hydrogel

    In situ gelation through photopolymerization for localized PDT

    [33]

    TiO2 and PEGDA

    TiO2

    Photopolymerisable hydrogel

    Inorganic/organic hybrid hydrogel system

    [34]

    PVA and sodium tetraborate

    MB

    Macrogels

    PS-loading hydrogel for drug-resistant bacterial killing

    [35]

    HEMA and MAA

    TMPyP

    Macrogels

    Localizing the photocytotoxic effect of PSs at a biomaterial surface for PACT

    [36]

    PMVE and MA

    MB

    Macrogels

    Electrically-responsive anti-adherent hydrogels for PACT

    [37]

    HPMC and chitosan

    TBO

    Macrogels

    PS-loaded hydrogels for the treatment of biofilm

    [38]

    PAA

    MB derivatives

    Macrogels

    PS-loaded hydrogel was found to be active for four-cycle PACT

    [39]

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