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

Abstract

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.

A novel polymer enabled by polymerized small molecule strategy for tumor photothermal and photodynamic therapy

“…7d). In addition, compared with the PBS, PYT NPs, NIR groups, the results of hematoxylin-eosin (H&E) and Ki67 staining (H&E and Ki67 staining method refers to previous reports [67][68][69][70][71]) showed that the tumor tissue in PYT NPs + NIR group disappeared at 12 days after irradiation, only connective tissue and granulation tissue were observed in irradiation region (Fig. 7e).…”

A Novel Polymer Enabled by Polymerized Small Molecule Strategy for Tumor Photothermal and Photodynamic Therapy

“…7d). In addition, compared with the PBS, PYT NPs, NIR groups, the results of hematoxylin-eosin (H&E) and Ki67 staining (H&E and Ki67 staining method refers to previous reports [45][46][47]) showed that the tumor tissue in PYT NPs + NIR group disappeared at 12 days after irradiation, only connective tissue and granulation tissue were observed in irradiation region (Fig. 7e).…”

A potent multifunctional ZIF-8 nanoplatform developed for colorectal cancer therapy by triple-delivery of chemo/radio/targeted therapy agents

“…The clinical application of nanoplatforms has been restricted due to significant concerns regarding their toxicity. 71 In order to address this issue, three major parameters, including body weight changes, pathological toxicity, and systematic distribution of treatment agents, were analyzed to assess the toxicity and biosafety of candidate formulations in immunocompromised C57BL/6 mice. Throughout the treatments, no significant weight loss was observed in all experimental groups (Fig.…”