Chitosan oligosaccharide decorated liposomes combined with TH302 for photodynamic therapy in triple negative breast cancer

Abstract

Background Triple negative breast cancer (TNBC) is an aggressive tumor with extremely high mortality that results from its lack of effective therapeutic targets. As an adhesion molecule related to tumorigenesis and tumor metastasis, cluster of differentiation-44 (also known as CD44) is overexpressed in TNBC. Moreover, CD44 can be effectively targeted by a specific hyaluronic acid analog, namely, chitosan oligosaccharide (CO). In this study, a CO-coated liposome was designed, with Photochlor (HPPH) as the 660 nm light mediated photosensitizer and evofosfamide (also known as TH302) as the hypoxia-activated prodrug. The obtained liposomes can help diagnose TNBC by fluorescence imaging and produce antitumor therapy by synergetic photodynamic therapy (PDT) and chemotherapy. Results Compared with the nontargeted liposomes, the targeted liposomes exhibited good biocompatibility and targeting capability in vitro; in vivo, the targeted liposomes exhibited much better fluorescence imaging capability. Additionally, liposomes loaded with HPPH and TH302 showed significantly better antitumor effects than the other monotherapy groups both in vitro and in vivo. Conclusion The impressive synergistic antitumor effects, together with the superior fluorescence imaging capability, good biocompatibility and minor side effects confers the liposomes with potential for future translational research in the diagnosis and CD44-overexpressing cancer therapy, especially TNBC. Graphic abstract

Synergistic Cascade Strategy Based on Modifying Tumor Microenvironment for Enhanced Breast Cancer Therapy

“…The second MW irradiation was dedicated to activate the sensitizer BML and to release the chemotherapy agent Ptx in the nanoparticles. Thirty 4T1 breast tumor-bearing mice were divided into five groups: PBS (control group, G1) ( Tajbakhsh et al, 2018 ), first MW + HA-BNPs@Ptx (G2) ( Thakur and Kutty, 2019 ), first MW + HA-BNPs + second MW (G3) ( Mu et al, 2017 ), HA-BNPs@Ptx + second MW (conventional SDDS, G4) ( Ding et al, 2021 ), and first MW + HA-BNPs@Ptx + second MW (G5) ( Hu et al, 2020 ). After treatment with mild hyperthermia (4-min MW exposure at 0.8 W cm −2 , G2, G3, and G5), PBS, HA-BNPs, or HA-BNPs@Ptx (0.5 μl/g, each microliter of nanoparticle suspension contained 0.434 μg of Ptx) was immediately injected into 4T1 breast tumor-bearing mice intravenously.…”

“…Despite the early detection and intervention, metastatic breast cancers remain largely incurable, especially triple-negative breast cancer (TNBC) ( Mu et al, 2017 ; Thakur and Kutty, 2019 ). TNBC is an aggressive subtype of breast cancer and accounts up to 10%–20% of all breast cancer cases ( Ding et al, 2021 ). Due to the lack of specific targets and high probability of metastasis, currently available treatment options are very limited ( Hu et al, 2020 ).…”

Recent Development of Photoresponsive Liposomes Based on Organic Photosensitizers, Au Nanoparticles, and Azobenzene Derivatives for Nanomedicine

“…From the development of the first generation of hematoporphyrin organic photosensitizers to the present, researchers have carried out a series of improvement works on the cytotoxicity, solubility, and phototoxicity issues of organic photosensitizers 64 and obtained various organic photosensitizers with different application scenarios. For example, Ding 65 used photochlor (HPPH) photosensitizer to design a photoresponsive liposome loaded with hypoxia-activated prodrug evofosfamide (TH302). The overexpression activity of adhesion molecule CD44 was inhibited by the mediation of 660 nm light, the activity of human breast cancer cells decreased by approximately 88.9%, and the volume ablation of tumor tissue reached approximately 90% after 1 week of incubation.…”

NIR-light-controlled G-quadruplex hydrogel for synergistically enhancing photodynamic therapy via sustained delivery of metformin and catalase-like activity in breast cancer

“…PDT, due to its high selectivity, non-invasiveness and lethal damage of tumour cells by generating tremendous cytotoxic ROS, becomes an attractive modality for anticancer therapy [ 2 ]. In the tumour microenvironment (TME), such PDT-induced antitumour process like apoptosis and necrosis was related to T cell-mediated immune responses through induction of immunogenic cell death (ICD) [ 3 , 4 ].…”