An Efficient Carbon‐Based Drug Delivery System for Cancer Therapy through the Nucleus Targeting and Mitochondria Mediated Apoptotic Pathway

Abstract

such as poor water solubility, [2] low bioavailability, rapid blood clearance, and multidrug resistance. [3] In order to solve these problems, drug delivery systems based on nanocarriers have been extensively developed, which not only increase the drug loading capacity and blood time of the target drug, but also reduce the potential systemic toxicity of the loaded drug. [4] So far, traditional nanocarriers are generally composed of inorganic materials such as carbon-based nanomaterials (CBNs), [5] magnetic particles, [6] silica, [7] gold-based nanomaterials, [8] and organic molecules such as polymer NPs, [9] liposomes, [10] micelles, [11] etc. Among them, CBNs have the characteristics of biocompatibility, low toxicity, high water-solubility, and potential to conjugate various molecules, they have been widely used in drug delivery, cancer diagnosis and therapy, and other fields, and are considered as an excellent nanocarrier. [12] It has been reported that CBNs loaded with DOX can be used to target tumor cell nucleus, but in order to improve the drug targeting rate, it is usually necessary to modify active targeting ligands, such as antibodies, folic acid, and peptides (RGD and nuclear targeting peptides), etc. However, these active targeting ligands have potential drawbacks while improving drug targeting, such as the high cost of antibodies and low tumor penetration due to their large size, the low stability of aptamers due to the nucleases in blood plasma, and the low circulating half-life of The emergence of nanocarriers solves the problems of antitumor drugs such as non-targeting, huge side effects, etc., and has been widely used in tumor therapy. Some kinds of antitumor drugs such as doxorubicin (DOX) mainly act on the nucleic acid causing DNA damage, interfering with transcription, and thereby disrupting or blocking the process of cancer cell replication. Herein, a new nanodrug delivery system, the carbon-based nanomaterials (CBNs)-Pluronic F127-DOX (CPD), is designed by using CBNs as a nanocarrier for DOX. As a result, the tumor growth inhibition rate of CPD group is as high as 79.42 ± 2.83%, and greatly reduces the side effects. The targeting rate of the CPD group of DOX in the tumor nucleus is 36.78%, and the %ID/g in tumor tissue is 30.09%. The CPD regulates the expression levels of Caspase-3, p53, and Bcl-2 genes by increasing intracellular reactive oxygen species (ROS) levels and reducing mitochondrial membrane potential, which indicates that mitochondrial-mediated pathways are involved in apoptosis. The CPD nanodrug delivery system increases the effective accumulation of DOX in tumor cell nuclei and tumor tissues, and generates massive ROS, thereby inhibiting tumor growth in vivo, representing a promising agent for anticancer applications.The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/smtd.202100539.

An Endogenous H2S-Activated Nanoplatform for Triple Synergistic Therapy of Colorectal Cancer

“…With the extra addition of H 2 O 2 , the greatest proportion of apoptotic cells was obtained with treatment with Cur-P@HMPB, indicating the much enhanced efficacy for HCT116 cells, in agreement with the results in Figure c. Notably, the Western blot results indicate that the Cur-P@HMPB group shows an obviously enhanced expression of apoptosis-related protein caspase-3, which could be attributed to the ROS-mediated mitochondrial damage (Figure e), further confirming the efficient treatment of HCT116 by Cur-P@HMPB.…”

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“…In addition, impairment of the mitochondria leads to decreased ATP production. 47–49 As shown in Fig. 3D, the intracellular ROS level (green fluorescence after staining with DCFH-DA) in H9C2 cells was increased after anoxia treatment, which however was significantly reduced after SPP/siE2F1 NC treatment.…”

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