Smart Chondroitin Sulfate Micelles for Effective Targeted Delivery of Doxorubicin Against Breast Cancer Metastasis.

Introduction: Metastasis is a major challenge in breast cancer therapy. The successful chemotherapy of breast cancer largely depends on the ability to block the metastatic process. Herein, we designed a dual-targeting and stimuli-responsive drug delivery system for targeted drug delivery against breast cancer metastasis. Methods: AS1411 aptamer-modified chondroitin sulfate A-ss-deoxycholic acid (ACSSD) was synthesized, and the unmodified CSSD was used as the control. Chemotherapeutic drug doxorubicin (DOX)-containing ACSSD (D-ACSSD) micelles were prepared by a dialysis method. The ACSSD conjugate was confirmed by Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), dynamic light scattering (DLS), and transmission electron microscopy (TEM). In vitro cellular uptake and cytotoxicity of D-ACSSD micelles were studied by confocal laser scanning microscopy (CLSM) and MTT assay in breast tumor cells. The inhibition capability of D-ACSSD micelles in cell migration and invasion was carried out in 4T1 cells. In vivo antitumor activity of DOX-containing micelles was investigated in metastatic 4T1-bearing Balb/c mice. Results: D-ACSSD and DOX-loaded CSSD (D-CSSD) micelles exhibited high drug encapsulation content and reduction-responsive characteristics. D-ACSSD micelles were spherical in shape. Compared with D-CSSD, D-ACSSD showed higher cellular uptake and more potent killing activity in 4T1 and MDA-MB-231 cells. Additionally, D-ACSSD exhibited stronger inhibitory effects on the invasion and migration of highly metastatic 4T1 cells than unmodified D-CSSD. Among the DOX-containing formulations, D-ACSSD micelles presented the most effective inhibition of tumor growth and lung metastasis in orthotopic 4T1-bearing mice in vivo. It also revealed that ACSSD micelles did not exhibit obvious systemic toxicity. Conclusion: The smart D-ACSSD micelles could be a promising delivery system for the therapy of metastatic breast cancer.

Paddle-Wheel-Shaped Porous Cu(II)-Organic Framework with Two Different Channels as an Absorbent for Methylene Blue.

The destruction of the ecological environment caused by human activity and modern industrial development is so severe that the water environment has become seriously polluted. Therefore, the exploration of high-efficiency absorbents has become one of the hot topics to solve this issue. Herein, a porous metal-organic framework [Cu(L)]·2.5H2O·0.5DMF (1, DMF = N,N-dimethylformamide) was successfully constructed using a rigid N-heterocyclic 5-(4-(1H,3,4-triazol-1-yl)phenyl)isophthalic acid (H2L) ligand. In particular, its structure includes the classical paddle-wheel-shaped secondary building units and two 1D channels with diameters of 7.2 and 3.2 Å, respectively. Complex 1 shows great sorption performance for methylene blue (MB) with a maximum capacity of 589 mg·g-1. The various influence factors, including the time, dye concentration, adsorbent dosage, and the pH of the solution, are investigated respectively. Also, the adsorption process is more in line with the first-order kinetics and the Langmuir isothermal adsorption model. The strong electrostatic force and intermolecular forces are primarily responsible for the remarkable adsorption ability of MB.