ROS-responsive liposomes with NIR light-triggered doxorubicin release for combinatorial therapy of breast cancer

Abstract

Background Reactive oxygen species (ROS)-responsive drug delivery systems (DDSs) are potential tools to minimize the side effects and substantially enhance the therapeutic efficacy of chemotherapy. However, it is challenging to achieve spatially and temporally controllable and accurate drug release in tumor sites based on ROS-responsive DDSs. To solve this problem, we designed a nanosystem combined photodynamic therapy (PDT) and ROS-responsive chemotherapy. Methods Indocyanine green (ICG), an ROS trigger and photosensitizer, and pB-DOX, a ROS-responsive prodrug of doxorubicin (DOX), were coencapsulated in polyethylene glycol modified liposomes (Lipo/pB-DOX/ICG) to construct a combination therapy nanosystem. The safety of nanosystem was assessed on normal HEK-293 cells, and the cellular uptake, intracellular ROS production capacity, target cell toxicity, and combined treatment effect were estimated on human breast cancer cells MDA-MB-231. In vivo biodistribution, biosafety assessment, and combination therapy effects were investigated based on MDA-MB-231 subcutaneous tumor model. Results Compared with DOX·HCl, Lipo/pB-DOX/ICG showed higher safety on normal cells. The toxicity of target cells of Lipo/pB-DOX/ICG was much higher than that of DOX·HCl, Lipo/pB-DOX, and Lipo/ICG. After endocytosis by MDA-MB-231 cells, Lipo/pB-DOX/ICG produced a large amount of ROS for PDT by laser irradiation, and pB-DOX was converted to DOX by ROS for chemotherapy. The cell inhibition rate of combination therapy reached up to 93.5 %. After the tail vein injection (DOX equivalent of 3.0 mg/kg, ICG of 3.5 mg/kg) in mice bearing MDA-MB-231 tumors, Lipo/pB-DOX/ICG continuously accumulated at the tumor site and reached the peak at 24 h post injection. Under irradiation at this time point, the tumors in Lipo/pB-DOX/ICG group almost disappeared with 94.9 % tumor growth inhibition, while those in the control groups were only partially inhibited. Negligible cardiotoxicity and no treatment-induced side effects were observed. Conclusions Lipo/pB-DOX/ICG is a novel tool for on-demand drug release at tumor site and also a promising candidate for controllable and accurate combinatorial tumor therapy.

Smart nanomaterials for cancer diagnosis and treatment

“…ROS-responsive liposome nanocarrier was also demonstrated for their synergistic antitumor effect in breast cancer cells with no cardiotoxicity or side-effects to normal cells as shown in Fig. 9 A, B [ 275 ].

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“…f Body weight curves of MDA-MB-231 tumor-bearing mice for each group. g Representative histological images of tumor and heart samples from the treated mice (Panel B ) [ 275 ] …”

Delivery of triptolide: a combination of traditional Chinese medicine and nanomedicine

“…As one of the most mature nanodelivery carriers, liposomes are one of the few nanoformulation that have been applied in clinical treatment, and their particle size ranges from 50–1000 nm [ 70 ]. Due to the special lipid bilayer structure, the water-soluble drugs can be encapsulated in the core and the lipid-soluble drugs can be encapsulated between the lipid bilayers [ 71 – 73 ]. The properties of liposomes, such as amphiphilicity, biocompatibility and biodegradation, are very valuable for the delivery of TCM.…”

NIR and Reduction Dual-Sensitive Polymeric Prodrug Nanoparticles for Bioimaging and Combined Chemo-Phototherapy

“…Among various multimodal therapies, chemo-phototherapy has been extensively investigated [8][9][10][11][12]. Phototherapy, mainly including PDT and PTT, is expected to possess many exclusive advantages, such as a noninvasive nature, high spatiotemporal controllability, diminutive side effects and negligible drug resistance [5,13,14]. On the other hand, PDT and PTT also face some bottleneck problems, including tumor hypoxia, insufficient light penetration depth and the heat resistance of the tumor cells [15].…”