Theranostic Agent Combining Fullerene Nanocrystals and Gold Nanoparticles for Photoacoustic Imaging and Photothermal Therapy

Developing photoactivatable theranostic platforms with integrated functionalities of biocompatibility, targeting, imaging contrast, and therapy is a promising approach for cancer diagnosis and therapy. Here, we report a theranostic agent based on a hybrid nanoparticle comprising fullerene nanocrystals and gold nanoparticles (FGNPs) for photoacoustic imaging and photothermal therapy. Compared to gold nanoparticles and fullerene crystals, FGNPs exhibited stronger photoacoustic signals and photothermal heating characteristics by irradiating light with an optimal wavelength. Our studies demonstrated that FGNPs could kill cancer cells due to their photothermal heating characteristics in vitro. Moreover, FGNPs that are accumulated in tumor tissue via the enhanced permeation and retention effect can visualize tumor tissue due to their photoacoustic signal in tumor xenograft model mice. The theranostic agent with FGNPs shows promise for cancer therapy

Folate-Appended β‑Cyclodextrin as a Promising Tumor Targeting Carrier for Antitumor Drugs <i>in Vitro</i> and <i>in Vivo</i>

A large number of antitumor drug delivery carriers based on passive targeting and/or active targeting have been developed. However, encapsulation of antitumor drugs into these drug carriers is often complicated, and antitumor activities of these targeting systems are not satisfactory. In the present study, we first prepared <i>heptakis</i>-6-folic acid (FA)-appended β-cyclodextrin (β-CyD) possessing two caproic acids between FA and a β-CyD molecule as a spacer (Fol-c₂-β-CyD) and evaluated the potential as a novel tumor targeting carrier for antitumor drugs through a complexation. Fol-c₂-β-CyD formed an inclusion complex with doxorubicin (DOX) at a 1:1 molar ratio with a markedly high stability constant (>10⁶ M^–1). Cellular uptake of DOX was increased by the addition of Fol-c₂-β-CyD in KB cells, a folate receptor-α (FR-α)-positive cell line. Additionally, Fol-c₂-β-CyD increased <i>in vitro</i> antitumor activities of antitumor drugs such as DOX, vinblastine (VBL), and paclitaxel (PTX) in KB cells, but not in A549 cells, a FR-α-negative cell line. The complex of DOX with Fol-c₂-β-CyD markedly increased antitumor activity of DOX, not only after intratumoral administration but also after intravenous administration to mice subcutaneously inoculated Colon-26 cells, a FR-α-positive cell line. These findings suggest that Fol-c₂-β-CyD could be useful as a promising antitumor drug carrier

Design and Evaluation of Folate-Appended α‑, β‑, and γ‑Cyclodextrins Having a Caproic Acid as a Tumor Selective Antitumor Drug Carrier in Vitro and in Vivo

We reported that <i>per</i>-6-folic acid (FA)-appended β-cyclodextrin (β-CyD) possessing two caproic acids between FA and a β-CyD molecule as a spacer (Fol-c₂-β-CyD) could be useful as a promising antitumor drug carrier. However, the effects of the cavity size and the spacer length on the carrier ability are not still known. In this study, we designed and evaluated the FA-appended three kinds of CyDs possessing a caproic acid as a spacer between FA and a CyD molecule (Fol-c₁-CyDs) as a tumor targeting carrier for antitumor drugs. The stability constant of the Fol-c₁-β-CyD/doxorubicin (DOX) complex was much higher than those of Fol-c₁-α-CyD and Fol-c₁-γ-CyD at pH 7.3. Antitumor activity of DOX was increased by the complexation with Fol-c₁-β-CyD, but not with Fol-c₁-α-CyD or Fol-c₁-γ-CyD in KB cells, a folate receptor-α-positive cell line. Also, Fol-c₁-β-CyD increased antitumor activities of paclitaxel and vinblastine, but not 5-fluorouracil. Furthermore, Fol-c₁-β-CyD accelerated cellular uptake of DOX and inhibited its efflux from KB cells. The Fol-c₁-β-CyD/DOX complex showed much higher antitumor activity than DOX alone after intratumoral and intravenous administrations to tumor-bearing mice with a negligible change of the blood chemistry values. These findings suggest that Fol-c₁-β-CyD could be useful as a tumor-selective carrier for antitumor drugs