Chondroitin Sulfate-Modified Liposomes for Targeted Co-Delivery of Doxorubicin and Retinoic Acid to Suppress Breast Cancer Lung Metastasis

Abstract

Breast cancer treatment remains challenging due to high levels of cell metastasis. Chemotherapy drug combinations can inhibit both tumor growth in situ and metastasis to distant organs. Therefore, here, we developed chondroitin sulfate liposomes (CSLs) as a carrier for the co-delivery of retinoic acid (RA) and doxorubicin (DOX) and examined their efficiency in suppressing lung metastasis of breast cancer. CSLs were prepared using CS–deoxycholic acid conjugates and found to encapsulate both RA and DOX via hydrophobic and hydrophilic interactions. The resulting DOX+RA-CSLs were uniformly spherical and showed good serum stability and encapsulation efficiency of 98.7% ± 1.3% for RA and 90.8% ± 2.9% for DOX. Pharmacodynamic experiments in vitro and in vivo also revealed that DOX+RA-CSLs had better anticancer and anti-metastatic activity than CS-free liposomes, single drug-loaded liposomes, and free drug solutions at the same dose (2 mg/kg DOX or RA). Our results suggest that this liposomal delivery system can effectively suppress lung metastasis of breast cancer.

Nanotechnology for the theranostic opportunity of breast cancer lung metastasis: recent advancements and future challenges

“…More and more novel nanoparticle-based targeted DDSs to improve the treatment of BCLM are being studied (Table 3) (Liu et al, 2018;Li et al, 2019a;Cheng et al, 2019;Xiong et al, 2019;Yu et al, 2019;Fan et al, 2020;Gong et al, 2020;Liu et al, 2020;Mu et al, 2020;Shi et al, 2021;Shi et al, 2021;Li et al, 2021;Zhang et al, 2021;Shi et al, 2023;Sabatelle et al, 2024). The process of DDSs to target the metastatic site can be divided into two steps, including one targeting the specific organ where the metastasis is located and the second targeting cancer cells or subcellular organs (Schroeder et al, 2011).…”

An Overview of Antitumour Activity of Polysaccharides

“…CS-based multi-walled carbon nanotubes can precisely target CD44 receptors overexpressed on triple-negative breast cancer specific cells [150]. In addition, combined application of CS with doxorubicin or quercetin (chemicalsensitizer) can enhance chemical photodynamic therapy and overcome multidrug resistance [151,152].…”

Estrone-Conjugated PEGylated Liposome Co-Loaded Paclitaxel and Carboplatin Improve Anti-Tumor Efficacy in Ovarian Cancer and Reduce Acute Toxicity of Chemo-Drugs

“…Therefore, the use of liposomes to achieve the delivery of chemo-drug is an efficient way, which can improve the therapeutic effect and reduce systemic toxicities. 40 Unsatisfactorily, conventional liposomes are easy to be taken by the cells of mononuclear phagocyte system (MPS) so that they are rapidly removed from blood. 41 In order to solve this problem, the surface of conventional liposomes is commonly coated with inert, biocompatible hydrophilic polymers, such as polyethylene glycol (PEG).…”