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Bioresponsive and near infrared photon co-enhanced cancer theranostic based on upconversion nanocapsules.

ABSTRACT: Developing nanotheranostics responsive to tumor microenvironments has attracted tremendous attention for on-demand cancer diagnosis and treatment. Herein, a facile Mn-doping strategy was adopted to transform mesoporous silica coated upconversion nanoparticles (UCNPs) to yolk-like upconversion nanostructures which possess a tumor-responsive biodegradation nature. The huge internal space of the innovated nanocarriers is suitable for doxorubicin (DOX) storage, besides, the Mn-doped shell is sensitive to the intratumoral acidity and reducibility, which enables shell biodegradation and further accelerates the breakage of Si-O-Si bonds within the silica framework. This tumor-responsive shell degradation is beneficial for realizing tumor-specific DOX release. Subsequently, polyoxometalate (POM) nanoclusters that can enhance photothermal conversion in response to the tumor reducibility and acidity were modified on the surface of the silica shell, thereby achieving NIR-enhanced shell degradation and also preventing premature DOX leakage. The as-produced thermal effect of the POM couples with the chemotherapy effect of the released DOX to perform a synergetic chemo-photothermal therapy. Additionally, the shell degradation brings size shrinkage to the nanocarriers, allowing faster nanoparticle diffusion and deeper tumor penetration, which is significant for improving theranostic outcomes. Also, the drastic decline of the red/green (R/G) ratio caused by the DOX release can be used to monitor the DOX release content through a fluorescence resonance energy transfer (FRET) method. The MRI effect caused by Mn release together with the MRI/CT/UCL imaging derived from Gd3+/Yb3+/Nd3+/Er3+ co-doped UCNPs under 808 nm laser excitation endow the nanosystem with multiple imaging capability, thus realizing imaging-guided cancer therapy.

SUBMITTER: Xu J

PROVIDER: S-EPMC5931193 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Bioresponsive and near infrared photon co-enhanced cancer theranostic based on upconversion nanocapsules.

Xu Jiating J Han Wei W Cheng Ziyong Z Yang Piaoping P Bi Huiting H Yang Dan D Niu Na N He Fei F Gai Shili S Lin Jun J

Chemical science 20180206 12

Developing nanotheranostics responsive to tumor microenvironments has attracted tremendous attention for on-demand cancer diagnosis and treatment. Herein, a facile Mn-doping strategy was adopted to transform mesoporous silica coated upconversion nanoparticles (UCNPs) to yolk-like upconversion nanostructures which possess a tumor-responsive biodegradation nature. The huge internal space of the innovated nanocarriers is suitable for doxorubicin (DOX) storage, besides, the Mn-doped shell is sensiti ...[more]

PMID: 29844897

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Project description:Photodynamic therapy (PDT) has been widely applied in the clinic for the treatment of various types of cancer due to its precise controllability, minimally invasive approach and high spatiotemporal accuracy as compared with conventional chemotherapy. However, the porphyrin-based photosensitizers (PSs) used in clinics generally suffer from aggregation-caused reductions in the generation of reactive oxygen species (ROS) and limited tissue penetration because of visible light activation, which greatly hampers their applications for the treatment of deep-seated tumors. Methods: We present a facile strategy for constructing a NIR-regulated cancer theranostic nanoplatform by encapsulating upconversion nanoparticles (UCNPs) and a luminogen (2-(2,6-bis((E)-4-(phenyl(40-(1,2,2-triphenylvinyl)-[1,10-biphenyl]-4-yl)amino)styryl)-4H-pyran-4-ylidene)malononitrile, TTD) with aggregation-induced emission (AIEgen) characteristics using an amphiphilic polymer, and further conjugating cyclic arginine-glycine-aspartic acid (cRGD) peptide to yield UCNP@TTD-cRGD NPs. We then evaluated the bioimaging and anti-tumor capability of the UCNP@TTD-cRGD NPs under NIR light illumination in an in vitro three-dimensional (3D) cancer spheroid and in a murine tumor model, respectively. Results: With a close match between the UCNP emission and absorption of the AIEgen, the synthesized NPs could efficiently generate ROS, even under excitation through thick tissues. The NIR-regulated UCNP@TTD-cRGD NPs that were developed could selectively light up the targeted cancer cells and significantly inhibit tumor growth during the NIR-regulated PDT treatment as compared with the cells under white light excitation. Conclusion: In summary, the synthesized UCNP@TTD-cRGD NPs showed great potential in NIR light-regulated photodynamic therapy of deep-seated tumors. Our study will inspire further exploration of novel theranostic nanoplatforms that combine UCNPs and various AIEgen PSs for the advancement of deep-seated tumor treatments with potential clinical translations.

Dataset Information

Bioresponsive and near infrared photon co-enhanced cancer theranostic based on upconversion nanocapsules.

Publications

Bioresponsive and near infrared photon co-enhanced cancer theranostic based on upconversion nanocapsules.

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