Introduction: The targeted delivery of anti-cancer drugs to tumor tissue has been recognized as a promising strategy to increase their therapeutic efficacy and reduce side effects. Mesoporous silica-coated superparamagnetic Fe3O4 nanoparticles (NH2-MSNs), a kind of nanocarrier, can passively enter tumor tissues to enhance the permeability and retention of drugs. However, NH2-MSNs do not specifically bind to cancer cells. This drawback encouraged us to develop a more efficient nanocarrier for cancer therapy. Methods: Herein, we describe the development of an effective nanocarrier based on NH2-MSNs, which were modified with hyaluronic acid on their surface (HA-MSNs) and loaded with doxorubicin (DOX). We have successfully fabricated uniform spherical HA-MSNs nanocarriers. The targeting ability of this delivery system was evaluated through specific uptake by cells and IVIS imaging. Results: DOX-HA-MSNs nanocarriers displayed more dramatic cytotoxic activity against 4T1 breast cancer cells compared to GES-1 gastric mucosa cells. In vivo results revealed that once DOX-HA-MSNs nanocarriers are exposed to an external magnetic field, they could be rapidly attracted to the magnet and effectively cross the cytoplasmic membrane via CD44 receptor-mediated transcytosis. This allows them to access the cancer cell cytoplasm and release DOX based on changes in the physiological environment. Both in vitro and in vivo results demonstrated that the HA-MSNs nanocarriers provided better therapeutic efficacy. Conclusion: The HA-MSNs nanocarriers represent an effective new paradigm to treat cancers due to active targeting to the tumor cells. Moreover, the specific uptake by the tumor effectively protects normal tissues to reduce off-target side effects. The reported findings support further investigation of HA-MSNs for cancer therapy.

The inherent radioresistance and inaccuracy of localization of tumors weaken the clinical implementation effectiveness of radiotherapy. To overcome these limitations, hyaluronic acid-functionalized bismuth oxide nanoparticles (HA-Bi₂O₃ NPs) were synthesized by one-pot hydrothermal method for target-specific computed tomography (CT) imaging and radiosensitization of tumor. After functionalization with hyaluronic acid, the Bi₂O₃ NPs possessed favorable solubility in water and excellent biocompatibility and were uptaken specifically by cancer cells overexpressing CD44 receptors. The as-prepared HA-Bi₂O₃ NPs exhibited high X-ray attenuation efficiency and ideal radiosensitivity via synergizing X-rays to induce cell apoptosis and arrest the cell cycle in a dose-dependent manner in vitro. Remarkably, these properties offered excellent performance in active-targeting CT imaging and enhancement of radiosensitivity for inhibition of tumor growth. These findings demonstrated that HA-Bi₂O₃ NPs as theranostic agents exhibit great promise for CT imaging-guided radiotherapy in diagnosis and treatment of tumors.

Carbon quantum dots (CDs) as emerging carbon nano-materials have attracted tremendous attention in biomedical fields due to unique properties. In this study, hyaluronate (HA) and polyethylenimine (PEI) functionalized carbon dots (HP-CDs) were synthesized by a facile bottom-up method for tumor targeting and gene delivery. After HA modification, the HP-CDs exhibited superior dispersibility in water and good biocompatibility and were internalized readily into the cytoplasm of cancer via HA-receptor mediated endocytosis. Meanwhile, the HP-CDs with PEI functionalization were shown to have excellent gene condensation capability via electrostatic attraction and protective capacity by preventing nuclease degradation. By virtue of good photoluminescence properties, the HP-CDs as a gene carrier were successfully applied to intracellular imaging and gene delivery. Taken together, the resultant HP-CDs displayed great potential in tumor targeting, intracellular imaging and gene delivery.

Photoluminescent carbon dots (CDs) with graphite-like phase structure have been widely reported. Herein, we first report nitrogen-doped carbon dots (NCDs) with heterogeneous multi-layered structures by bottom-up hydrothermal carbonization process. The formation and surface passivation of NCDs was accomplished simultaneously. The as-prepared NCDs possess stable photoluminescence, solubility in water and various functional groups on their surface. XRD results clearly showed that there were two kinds of interlayer lattice spaces in the phase structure of prepared NCDs, which corresponded to the {002} plane of graphite and the {001} plane of graphite oxide. We further demonstrated that NCDs with good biocompatibility were easily and quickly internalized by cancer cells and are particularly suitable for multicolour real-time cellular imaging.

Background: Therapeutic tumor vaccine (TTV) that induces tumor-specific immunity has enormous potentials in tumor treatment, but high heterogeneity and poor immunogenicity of tumor seriously impair its clinical efficacy. Herein, a novel NIR responsive tumor vaccine in situ (HA-PDA@IQ/DOX HG) was prepared by integrating hyaluronic acid functionalized polydopamine nanoparticles (HA-PDA NPs) with immune adjuvants (Imiquimod, IQ) and doxorubicin (DOX) into thermal-sensitive hydrogel. Results: HA-PDA@IQ NPs with high photothermal conversion efficiency (41.2%) and T₁-relaxation efficiency were using HA as stabilizer by the one-pot oxidative polymerization. Then, HA-PDA@IQ loaded DOX via π-π stacking and mixed with thermal-sensitive hydrogel to form the HA-PDA@IQ/DOX HG. The hydrogel-confined delivery mode endowed HA-PDA@IQ/DOX NPs with multiple photothermal ablation performance once injection upon NIR irradiation due to the prolonged retention in tumor site. More importantly, this mode enabled HA-PDA@IQ/DOX NPs to promote the DC maturation, memory T cells in lymphatic node as well as cytotoxic T lymphocytes in spleen. Conclusion: Taken together, the HA-PDA@IQ/DOX HG could be served as a theranostic tumor vaccine for complete photothermal ablation to trigger robust antitumor immune responses.