Original Articles
A traceable nanoplatform for enhanced chemo-photodynamic therapy by reducing oxygen consumption

https://doi.org/10.1016/j.nano.2019.03.001Get rights and content

Abstract

Tumor hypoxia impedes the efficiencies of oxygen-dependent photodynamic therapy (PDT) and chemotherapy. Herein, we design a traceable nanoplatform (DOX/Met/BSA-HA-CDs) by reducing oxygen (O2) consumption to overcome the hypoxia-caused cancer therapy. Carbon dots (CDs) are used not only as a PDT agent but also applied for in vivo traceable imaging. Metformin (Met), a potent antihyperglycemic agent, to improve tumor oxygenation and enhance the efficiencies of hypoxia-caused cancer therapy. In the hypoxic tumor microenvironment, Met was released more rapidly than DOX, which is advantageous for improving hypoxic cancer to exert a better therapeutic efficiency. Ex vivo immunofluorescence staining revealed that the DOX/Met/BSA-HA-CDs nanoparticles greatly reduce O2 consumption in tumor site. Followed by in vivo synergistic treatment achieved considerably enhanced cancer therapeutic efficiency. This system holds great clinical promise as a traceable imaging approach to guide the improvement of PDT and chemotherapy efficiencies through utilizing a simple, safe method improved hypoxic tumor microenvironment.

Graphical Abstract

In this work, we utilized metformin (Met), a potent antihyperglycemic agent, to improve tumor oxygenation and subsequently enhance the efficiencies of hypoxia-caused photodynamic therapy (PDT) and chemotherapy. Carbon dots (CDs) can be applied as a PDT agent for simultaneous traceable imaging and cancer treatment. In the hypoxic tumor microenvironment, Met was released rapidly than DOX, which is advantageous for improving hypoxic cancer to exert a better therapeutic efficiency. Therefore, the DOX/Met/BSA-HA-CDs nanoparticles hold great clinical promise as a traceable imaging approach to guide the improvement of PDT and chemotherapy efficiencies through utilizing a simple, safe strategy to improve hypoxic tumor microenvironment.

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Section snippets

Background

Tumor hypoxia, resulting from an imbalance between the supply and consumption of oxygen (O2), is a characteristic feature of solid tumors.1., 2. Available O2 is consumed by irregular cancer cells proliferation at the tumor periphery, thereby limiting the diffusion of O2 into the deep layers of tumors, causing local hypoxia as well as acidulated environment.3 It is well documented that the occurrence of hypoxia is associated with most medical therapies, particularly radiotherapy and photodynamic

Preparation and characterization of DOX/Met/BSA-HA-CDs

Details of the experiments about preparation and characterization of DOX/Met/BSA-HA-CDs were described in the Supplementary data.

Cell uptake of DOX

Cellular uptake was observed by fluorescence microscopy (Zeiss LSM 510, Thornwood, NY, USA). Cells were seeded in 6-well culture plates at a density of 1 × 105 cells per well and allowed to adhere for 24 h. Then cells were exposed to 5 μg/mL equivalent DOX solution and DOX/Met/BSA-HA. For MCF-7 cells (Human breast carcinoma cell lines), after incubation for 4 h, the

Synthesis and characterization of CDs

In previous studies, CDs were synthesized by using citric acid as a carbon precursor and formamide was chose as a modifier to provide amino group for CDs. The as-produced CDs were water-dispersible, and the color of its solution was dark brown. The morphology of the CDs was characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS). From Figure 2, A, it can be seen that the CDs had a uniform dispersion without any apparent aggregation, and the diameters of

Discussion

In this paper, DOX and Met loaded BSA-HA-CDs nanoparticles were produced for tumor diagnosis and therapy. Firstly, HA-CDs conjugates were synthesized by amide bond formation between carboxyl groups of HA and amine groups of CDs in water using EDC and NHS chemistry. Secondly, HA-CDs conjugates were attached to BSA performed by employing EDC and NHS, in which the reducing-end carbonyl group of HA was conjugated to the amino group of BSA. DOX and Met loaded BSA-HA-CDs nanoparticles were produced

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    The authors declare no conflict of interest.

    This work was supported by grants from the National Natural Science Foundation of China (81503038).

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