A Highly Efficient Tumor‐Targeting Nanoprobe with a Novel Cell Membrane Permeability Mechanism

Abstract

Efficient tumor targeting has been a great challenge in the clinic for a very long time. The traditional targeting methods based on enhanced permeability and retention (EPR) effects show only an ≈5% targeting rate. To solve this problem, a new graphene‐based tumor cell nuclear targeting fluorescent nanoprobe (GTTN), with a new tumor‐targeting mechanism, is developed. GTTN is a graphene‐like single‐crystalline structure amphiphilic fluorescent probe with a periphery that is functionalized by sulfonic and hydroxyl groups. This probe has the characteristic of specific tumor cell targeting, as it can directly cross the cell membrane and specifically target to the tumor cell nucleus by the changed permeability of the tumor cell membranes in the tumor tissue. This new targeting mechanism is named the cell membrane permeability targeting (CMPT) mechanism, which is very different from the EPR effect. These probes can recognize tumor tissue at a very early stage and track the invasion and metastasis of tumor cells at the single cell level. The tumor‐targeting rate is improved from less than 5% to more than 50%. This achievement in efficient and accurate tumor cell targeting will speed up the arrival of a new era of tumor diagnosis and treatment.

Safety Issue of Changed Nanotoxicity of Zinc Oxide Nanoparticles in the Multicomponent System

“…TiO 2 NPs have the function of adsorbing ions due to their small particle size and enormous specific surface area, facilitating more rapid adsorption of ions than the equivalent bulk material . The 5 nm TiO 2 NPs adsorb free Zn 2+ dissolved in the medium and are suspended in the medium due to their good water solubility, reducing the toxicity of ZnO NPs because they do not have access to get into cells . The 25 nm TiO 2 NPs also possess absorption capacity like 5 nm TiO 2 NPs; some adhere to the surface of the cell membrane due to the poor water solubility, and some are taken by cells .…”

Altering sub-cellular location for bioimaging by engineering the carbon based fluorescent nanoprobe

“…However, the specific capability of GTTN targeting to cancer in vivo and further targeting to cancer cell nuclei was found due to the difference of cell membrane permeabilities between tumor cells and normal cells. Based on this phenomenon, we proposed a new targeting mechanism, named as the cell membrane permeability targeting (CMPT) mechanism [50]. Compared with our previous work, the S-GQDs in this paper are expected to be a new fluorescent probe owing to its low toxicity, transmembrane transport, cellular distribution in lysosome, excellent biocompatibility and high PL QY.…”

“…FT-IR spectra of fresh S-GQDs, S-GQDs & urine and S-GQDs excreted from urine show a significant difference, revealing that the S-GQDs are not like the GTTN which is stable in vivo (Fig. S7b) [50]. For in vivo toxicity, the six parameters of serum biochemistry increased gradually after 2 h injection and all the indicators recovered to the normal ranges after 24 h injection ( Fig.…”

“…They have strong fluorescence, but show high toxicity in vitro and in vivo. While negatively charged sulfonic-GQDs, which have been reported as graphene-based tumor cell nuclei-targeting fluorescent nanoprobes (GTTNs) [50], cannot pass through the cell membrane even after co-incubation for 48 h under normal culture conditions. However, the specific capability of GTTN targeting to cancer in vivo and further targeting to cancer cell nuclei was found due to the difference of cell membrane permeabilities between tumor cells and normal cells.…”

Tumor Targeting Strategies of Smart Fluorescent Nanoparticles and Their Applications in Cancer Diagnosis and Treatment

“…Beyond that, we will also introduce the new targeting strategy called CMPT proposed by Wang's group, which improves the tumor-targeting rate from less than 5% of the EPR effect to more than 50%. [37] The CMPT mechanism will stimulate new insights for the targeting design, accelerate the development of tumor precision medicine, and contribute to cancer treatment and early diagnosis.…”