Mitochondria and Nuclei Dual-Targeted Hollow Carbon Nanospheres for Cancer Chemophotodynamic Synergistic Therapy

Abstract

Dual-targeted nanoparticles are gaining increasing importance as a more effective anticancer strategy by attacking double key sites of tumor cells, especially in chemophotodynamic therapy. To retain the nuclei inhibition effect and enhance doxorubicin (DOX)-induced apoptosis by mitochondrial pathways simultaneously, we synthesized the novel nanocarrier (HKH) based on hollow carbon nitride nanosphere (HCNS) modified with hyaluronic acid (HA) and the mitochondrial localizing peptide D[KLAKLAK]2 (KLA). DOX-loaded HKH nanoparticles (HKHDs) showed satisfactory drug-loading efficiency, excellent solubility, and very low hemolytic effect. HA/CD44 binding and electrostatic attraction between positively charged KLA and A549 cells facilitated HKHD uptake via the endocytosis mechanism. Acidic microenvironment, hyaluronidase, and KLA targeting together facilitate doxorubicin toward the mitochondria and nuclei, resulting in apoptosis, DNA intercalation, cell-cycle arrest at the S phase, and light-induced reactive oxygen species production. Intravascular HKHD inhibited tumor growth in A549-implanted mice with good safety. The present study, for the first time, systemically reveals biostability, targetability, chemophotodynamics, and safety of the functionalized novel HKHD.

An in Situ Template for the Synthesis of Tunable Hollow Carbon Particles for High-Performance Lithium–Sulfur Batteries

“…Previous results have confirmed the role of carbon as the host for sulfur. 9−11 Recently, some efforts have focused on using hollow carbon particles as substrates due to their intriguing hollow structures. 30−32 However, the electrochemical properties have always been studied under a relative low current density (e.g., 0.1, 0.25 C, wherein 1 C = 1675 mA g –1 ) due to the intrinsic fast capacity degradation of Li–S battery systems, especially at high current densities.…”

“…To date, research has focused on the use of varied carbon materials in lithium–sulfur batteries because nanostructured carbon materials such as layered graphene (oxide), carbon nanotubes, and porous carbon play a critical role in embedding sulfur, enhancing the conductivity of electrodes, and suppressing diffusion of the polysulfide intermediates in order to maintain good cyclic performance. Previous results have confirmed the role of carbon as the host for sulfur. − Recently, some efforts have focused on using hollow carbon particles as substrates due to their intriguing hollow structures. − However, the electrochemical properties have always been studied under a relative low current density (e.g., 0.1, 0.25 C, wherein 1 C = 1675 mA g –1 ) due to the intrinsic fast capacity degradation of Li–S battery systems, especially at high current densities. Herein, we investigated the performances of three kinds of hollow carbon particles in lithium–sulfur applications at a high current density (e.g., 1 C) and found that one type showed good performance.…”

“…Hollow carbon nano- and microparticles have widespread applications in the fields of catalysis, electrochemistry, , energy (e,g., dye-sensitized solar cells), supercapacitors, rechargeable batteries, − and biotechnology , due to their hollow structure, physical stability, chemical inertness, high conductivity, and biocompatibility. To date, the most commonly used synthesis approach has been the well-known hard-template method, the steps of which usually consist of the synthesis of core particles as a template followed by coating the presynthesized core particles (e.g., silica gel, polystyrene, or metal (oxide) nanoparticles , ) with a layer of carbon and finally removing the core to form a hollow structure.…”

Mito‐Bomb: Targeting Mitochondria for Cancer Therapy

“…Moreover, DOX was also synthesized with HA, hollow carbon nitride nanosphere and a delocalized positively charged cationic apoptotic peptides KLA to obtain nanoparticles, HKHD. [ 86 ] HKHD was directed by KLA to target mitochondria. In the presence of light irradiation, it directly generated ROS, which led to apoptosis.…”

Precise design strategies of nanomedicine for improving cancer therapeutic efficacy using subcellular targeting

“…Therefore, in the rational design of subcellular targeting anticancer nanomedicine, we need to use dual-targeting strategies, taking into account both cancer cell targeting and subcellular targeting. For example, Qu's team 112 designed folate and TAT-modified Fe 3 O 4 core/mesoporous silica shell NPs to deliver camptothecin, López et al 113 developed mesoporous silica particles with asymmetric modification of folate and TPP, and Xie et al 114 constructed hollow carbonitride nanospheres modified by hyaluronic acid (HA) and mitochondrial localization peptide D. These NDDSs achieved the organic combination of cancer enrichment and subcellular level targeting, which greatly improving the efficiency of the antitumor agents. Furthermore, it should be noted that the overlapping interactions between two target ligands and their relative densities may have influences on their targeting ability.…”