A highly tumor-specific light-triggerable drug carrier responds to hypoxic tumor conditions for effective tumor treatment

Park, Wooram; Bae, Byoung-chan; Na, Kun

doi:10.1016/j.biomaterials.2015.11.014

Cited by 71 publications

(41 citation statements)

References 45 publications

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“…[14] Although these polymeric prodrugs can avert drug leakage during circulation in vivo,the release of drugs in tumor is uncontrollable due to the heterogeneity of tumor cells. [15] To release PSs at the tumor sites,e xogenous stimuli-responsive PS delivery systems also have been constructed, such as thermo- [16] and light- [17] sensitive nanoparticle systems.O wing to the non-invasive nature and the potential of precise spatiotemporal control, ar ange of photo-responsive systems have been engineered using exogenous light irradiation. [18] However,most of photochromic moieties,s uch as azobenzene, [19] suffer from various drawbacks,s uch as low penetration depth and skin injury because of the harmful UV light response.A lthough upconverting nanoparticles (UCNPs) [20] have been proposed to convert near infrared (NIR) light to UV light to overcome this limitation, the low energy conversion efficiencya nd expensive cost still exist in treatments.…”

Section: Introductionmentioning

confidence: 99%

Self‐Amplified Photodynamic Therapy through the ¹O₂‐Mediated Internalization of Photosensitizers from a Ppa‐Bearing Block Copolymer

Cao

Xue

et al. 2020

Angewandte Chemie

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Nanocarriers are employed to deliver photosensitizers for photodynamic therapy (PDT) through the enhanced penetration and retention effect, but disadvantages including the premature leakage and non‐selective release of photosensitizers still exist. Herein, we report a 1O2‐responsive block copolymer (POEGMA‐b‐P(MAA‐co‐VSPpaMA) to enhance PDT via the controllable release of photosensitizers. Once nanoparticles formed by the block copolymer have accumulated in a tumor and have been taken up by cancer cells, pyropheophorbide a (Ppa) could be controllably released by singlet oxygen (1O2) generated by light irradiation, enhancing the photosensitization. This was demonstrated by confocal laser scanning microscopy and in vivo fluorescence imaging. The 1O2‐responsiveness of POEGMA‐b‐P(MAA‐co‐VSPpaMA) block copolymer enabled the realization of self‐amplified photodynamic therapy by the regulation of Ppa release using NIR illumination. This may provide a new insight into the design of precise PDT.

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Section: Introductionmentioning

confidence: 99%

Self‐Amplified Photodynamic Therapy through the ¹O₂‐Mediated Internalization of Photosensitizers from a Ppa‐Bearing Block Copolymer

Cao

Xue

et al. 2020

Angewandte Chemie

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“…In order to further confirm the ROS types generated by UTMs, we chose a fluorogenic ROS Type 1 probe dihydroethidium (DHE) to detect ROS Type 1 (•OH and

{normalO}_{2}^{• -}

) . DHE is able to be degraded to ethidium (E + ) and 2‐hydroxyethidium (2‐OH‐E + ) by ROS Type 1 , which can emit strong red fluorescence once intercalating into DNA of cell nuclei.…”

Section: Resultsmentioning

confidence: 99%

An O₂ Self‐Supplementing and Reactive‐Oxygen‐Species‐Circulating Amplified Nanoplatform via H₂O/H₂O₂ Splitting for Tumor Imaging and Photodynamic Therapy

Zhang

Chen

Liu

et al. 2017

Adv Funct Materials

192

116

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Conventional photodynamic therapy (PDT) has limited applications in clinical cancer therapy due to the insufficient O 2 supply, inefficient reactive oxygen species (ROS) generation, and low penetration depth of light. In this work, a multifunctional nanoplatform, upconversion nanoparticles (UCNPs)@TiO 2 @ MnO 2 core/shell/sheet nanocomposites (UTMs), is designed and constructed to overcome these drawbacks by generating O 2 in situ, amplifying the content of singlet oxygen ( 1 O 2 ) and hydroxyl radical (·OH) via water-splitting, and utilizing 980 nm near-infrared (NIR) light to increase penetration depth. Once UTMs are accumulated at tumor site, intracellular H 2 O 2 is catalyzed by MnO 2 nanosheets to generate O 2 for improving oxygen-dependent PDT. Simultaneously, with the decomposition of MnO 2 nanosheets and 980 nm NIR irradiation, UCNPs can efficiently convert NIR to ultraviolet light to activate TiO 2 and generate toxic ROS for deep tumor therapy. In addition, UCNPs and decomposed Mn 2+ can be used for further upconversion luminescence and magnetic resonance imaging in tumor site. Both in vitro and in vivo experiments demonstrate that this nanoplatform can significantly improve PDT efficiency with tumor imaging capability, which will find great potential in the fight against tumor. Scheme 1. Schematic illustration of UTMs for O 2 self-supplemented and ROS circulating amplified PDT. A) Fabrication of UTMs nanoplatform by combining UCNPs@TiO 2 nanoparticles and MnO 2 nanosheets. B) EPR effect mediated tumor accumulation and cellular uptake of UTMs. C) Intracellular decomposition of MnO 2 nanosheets to produce O 2 and NIR-activated catalysis of TiO 2 nanoshells to induce ROS ( 1 O 2 and ·OH) generation via H 2 O 2 and H 2 O splitting reactions. D) The detailed mechanisms of circulating amplified ROS generation: NIR-activated energy transfer to emit UV light via UCNPs; UV-excited electrons transfer from valence band (VB) to conduction band (CB) of TiO 2 nanoshells to further catalyze O 2 and H 2 O to generate 1 O 2 , O 2 •− and ·OH; MnO 2 nanosheets-catalyzed production of O 2 via H 2 O 2 splitting to further enhance O 2 concentration, and finally intracellular superoxide dismutase (SOD) for converting O 2 •− back to O 2 and H 2 O 2 to put a perfect ending on ROS circulating amplified reactions. E) All the corresponding reactions of various components (MnO 2 , TiO 2 , and SOD) and their interrelations for circulating amplified ROS generation. www.afm-journal.de www.advancedsciencenews.com 1700626 (3 of 14)

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“…The electron rich chondroitin sulfate (CS) is known to promote generation of type I ROS, making it a suitable ROS‐degradable carrier under hypoxic conditions. By decorating a PS on CS backbone, a DDS responsive to both external (light) and internal (tumor hypoxia) stimuli was constructed . The DDS consists of a CS‐PS (pheophorbide) conjugate which forms NPs with loaded DOX.…”

Section: Multiple‐stimuli Responsive Ddssmentioning

confidence: 99%

ROS‐responsive drug delivery systems

Liang

Liu

2016

Bioengineering & Transla Med

190

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Reactive oxygen species (ROS) play an important role in signal transduction and metabolism. Over‐produced ROS in cells or tissues, however, often leads to oxidation stress that has implications in a series of diseases including cancer, aging, atherosclerosis and inflammation. Driven by the need for on‐demand drug delivery and fuelled by recent development of ROS‐responsive materials and nanomedicine, responsive drug delivery systems (DDSs) have gained increasing research interest. ROS‐responsive DDS is designed to release therapeutic agents only in targets of interest that produce excessive ROS, which may lead to both enhanced therapeutic efficiency and reduced side effects. Multiple‐stimuli responsive DDSs that are also sensitive to other stimuli can further enhance controlled drug release in sites where multiple stimuli coexist. Beyond drug delivery, multifunctional DDSs have great potential in achieving simultaneous imaging, combinatorial therapy and targeting ability by introducing multifunctional elements such as signal reporter, targeting elements and photosensitizer. This review will summarize the latest development of ROS‐responsive DDSs and discuss their design principle and biomedical applications.

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A highly tumor-specific light-triggerable drug carrier responds to hypoxic tumor conditions for effective tumor treatment

Cited by 71 publications

References 45 publications

Self‐Amplified Photodynamic Therapy through the ¹O₂‐Mediated Internalization of Photosensitizers from a Ppa‐Bearing Block Copolymer

Self‐Amplified Photodynamic Therapy through the ¹O₂‐Mediated Internalization of Photosensitizers from a Ppa‐Bearing Block Copolymer

An O₂ Self‐Supplementing and Reactive‐Oxygen‐Species‐Circulating Amplified Nanoplatform via H₂O/H₂O₂ Splitting for Tumor Imaging and Photodynamic Therapy

ROS‐responsive drug delivery systems

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A highly tumor-specific light-triggerable drug carrier responds to hypoxic tumor conditions for effective tumor treatment

Cited by 71 publications

References 45 publications

Self‐Amplified Photodynamic Therapy through the 1O2‐Mediated Internalization of Photosensitizers from a Ppa‐Bearing Block Copolymer

Self‐Amplified Photodynamic Therapy through the 1O2‐Mediated Internalization of Photosensitizers from a Ppa‐Bearing Block Copolymer

An O2 Self‐Supplementing and Reactive‐Oxygen‐Species‐Circulating Amplified Nanoplatform via H2O/H2O2 Splitting for Tumor Imaging and Photodynamic Therapy

ROS‐responsive drug delivery systems

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Self‐Amplified Photodynamic Therapy through the ¹O₂‐Mediated Internalization of Photosensitizers from a Ppa‐Bearing Block Copolymer

Self‐Amplified Photodynamic Therapy through the ¹O₂‐Mediated Internalization of Photosensitizers from a Ppa‐Bearing Block Copolymer

An O₂ Self‐Supplementing and Reactive‐Oxygen‐Species‐Circulating Amplified Nanoplatform via H₂O/H₂O₂ Splitting for Tumor Imaging and Photodynamic Therapy