The aim of this research is to utilize a hybrid system of liposomal doxorubicin (DOX-Lip) loaded thermogel (DOX-Lip-Gel) to realize the steady sustained delivery of doxorubicin (DOX), a small hydrophilic drug, for the treatment of breast cancer locally. Herein, liposomal doxorubicin was prepared via the traditional film dispersion method with the particle size of 75 nm and drug entrapment efficiency of 86%. And, the triblock copolymer of poly (D, L-lactide-co-glycolide)-b-poly (ethylene glycol)-b-poly (D, L-lactide -co-glycolide) (PLGA-PEG-PLGA) was synthesized via ring-opening polymerization to prepare the thermosensitive hydrogel through dissolving the polymers in DOX-Lip solution. The liposome loaded hydrogel was in a sol state at room temperature and converted into the gel state at body temperature and would degrade gradually during the time in vivo. The drug release of DOX out of DOX-Lip-Gel could be in a steady sustained manner up to 11 days without significant burst release as compared to that of DOX-loaded hydrogel (DOX-Gel). An orthotopic breast cancer model was adopted to evaluate the in vivo antitumor efficacy. And, the results revealed DOX-Lip-Gel had better antitumor efficiency as well as lower side effects.

Novel breast carcinoma dual-targeted redox-responsive nanoparticles (NPs) based on cholesteryl-hyaluronic acid conjugates were designed for intracellular delivery of the antitumor drug doxorubicin (DOX). A series of reduction-responsive hyaluronic acid derivatives grafted with hydrophobic cho­lesteryl moiety (HA-ss-Chol) and GE11 peptide conjugated HA-ss-Chol (GE11–HA-ss-Chol) were synthesized. The obtained conjugates showed attractive self-assembly characteristics and high drug loading capacity. GE11–HA-ss-Chol NPs were highly stable under conditions mimicking normal physiological conditions, while showing a fast degradation of the vehicle’s structure and accelerating the drug release dramatically in the presence of intracellular reductive environment. Furthermore, the cellular uptake assay confirmed GE11–HA-ss-Chol NPs were taken up by MDA-MB-231 cells through CD44- and epidermal growth factor receptor-mediated endocytosis. The internalization pathways of GE11–HA-ss-Chol NPs might involve clathrin-mediated endocytosis and macropinocytosis. The intracellular distribution of DOX in GE11–HA-ss-Chol NPs showed a faster release and more efficient nuclear delivery than the insensitive control. Enhanced in vitro cytotoxicity of GE11–HA-ss-Chol DOX-NPs further confirmed the superiority of their dual-targeting and redox-responsive capacity. Moreover, in vivo imaging investigation in MDA-MB-231 tumor-bearing mice confirmed that GE11–HA-ss-Chol NPs labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide, a near-infrared fluorescence dye, possessed a preferable tumor accumulation ability as compared to the single-targeting counterpart (HA-ss-Chol NPs). The antitumor efficacy showed an improved therapy efficacy and lower systemic side effect. These results suggest GE11–HA-ss-Chol NPs provide a good potential platform for antitumor drugs.

Liver cancer has become one of the most common fatal cancers worldwide, with morbidity rates increasing each year. Wogonin (WG) is an attractive candidate for the development of new anti-cancer drugs. In this study, a novel glycyrrhetinic acid (GA)-modified WG liposome was developed for use in targeted anti-cancer therapy. Three types of WG preparations were investigated: free wogonin in solution (WG), passively targeted wogonin liposomes (WG-Lip) and GA-modified wogonin liposomes (GA-WG-Lip). The entrapment efficiency, size and zeta potential were measured. Cellular uptake, cytotoxicity, in vivo bio-distribution and anti-tumor efficacy were also investigated. Addition of GA to the liposomes did not diminish the high entrapment efficiency observed in the liposomes without GA. GA-WG-Lip showed the greatest uptake and had an IC₅₀ value 1.46 times higher than that of WG-Lip. The GA-modified liposomes rapidly accumulated in the liver with a long retention time, and also displayed a better tumor inhibitory ratio than that of the unmodified liposomes. Overall, the data indicated that use of the GA-modified WG liposomes conferred improvements in bio-distribution, accumulation at the tumor and therapeutic efficacy, perhaps due to increased receptor-mediated uptake of liposomes by liver-targeted cells. Together, these data show that GA-WG-Lip is a promising means of targeted therapy for liver cancer.