Biomimetic oxygen delivery nanoparticles for enhancing photodynamic therapy in triple-negative breast cancer

Abstract

Background Triple-negative breast cancer (TNBC) is a kind of aggressive breast cancer with a high rate of metastasis, poor overall survival time, and a low response to targeted therapies. To improve the therapeutic efficacy and overcome the drug resistance of TNBC treatments, here we developed the cancer cell membrane-coated oxygen delivery nanoprobe, CCm–HSA–ICG–PFTBA, which can improve the hypoxia at tumor sites and enhance the therapeutic efficacy of the photodynamic therapy (PDT), resulting in relieving the tumor growth in TNBC xenografts. Results The size of the CCm–HSA–ICG–PFTBA was 131.3 ± 1.08 nm. The in vitro 1O2 and ROS concentrations of the CCm–HSA–ICG–PFTBA group were both significantly higher than those of the other groups (P < 0.001). In vivo fluorescence imaging revealed that the best time window was at 24 h post-injection of the CCm–HSA–ICG–PFTBA. Both in vivo 18F-FMISO PET imaging and ex vivo immunofluorescence staining results exhibited that the tumor hypoxia was significantly improved at 24 h post-injection of the CCm–HSA–ICG–PFTBA. For in vivo PDT treatment, the tumor volume and weight of the CCm–HSA–ICG–PFTBA with NIR group were both the smallest among all the groups and significantly decreased compared to the untreated group (P < 0.01). No obvious biotoxicity was observed by the injection of CCm–HSA–ICG–PFTBA till 14 days. Conclusions By using the high oxygen solubility of perfluorocarbon (PFC) and the homologous targeting ability of cancer cell membranes, CCm–HSA–ICG–PFTBA can target tumor tissues, mitigate the hypoxia of the tumor microenvironment, and enhance the PDT efficacy in TNBC xenografts. Furthermore, the HSA, ICG, and PFC are all FDA-approved materials, which render the nanoparticles highly biocompatible and enhance the potential for clinical translation in the treatment of TNBC patients.

Research Progress on Cell Membrane-Coated Biomimetic Delivery Systems

“…The cancer cell membrane is used for targeting and immune escape, and a biomimetic system has been prepared for scanning imaging and photodynamic therapy. The experimental results showed that the system had a higher oxygen capacity, and fluorescence imaging in vivo showed that the fluorescence intensity of the system was stronger and exhibited increased duration, and that the system could significantly inhibit tumor growth ( Fang et al, 2021 ). Zhang et al (2019) developed novel O 2 -evolved PDT NPs for homologous cancer cell targeting and dual-mode imaging (magnetic resonance imaging and fluorescence imaging).…”

Progress in Nanocarriers Codelivery System to Enhance the Anticancer Effect of Photodynamic Therapy

“…Common oxygen transport carriers include nanoscale artificial red blood cell tumors targeting human serum albumin, which can deliver oxygen-loaded hemoglobin and PSs to the tumor site [52,53]. Perfluorocarbon (PFC), an artificial blood substitute that can dissolve large amounts of oxygen, can also alleviate tumor hypoxia after cotargeted delivery with PS [54]. Another method is to use metal carriers to react with peroxide to generate oxygen at tumor sites [55,56].…”

NIR-II-driven and glutathione depletion-enhanced hypoxia-irrelevant free radical nanogenerator for combined cancer therapy

“…However, hypoxia as a characteristic hallmark in solid tumors has been demonstrated to seriously hinder the performance of oxygen-dependent PDT. Besides, conventional PDT agents are usually activated by shorter wavelength lasers which are known to have only limited tissue penetration [ 4 – 6 ]. In view of these considerations, the use of free radical initiator, 2,2′-azobis[2-(2-imidazolin-2-yl)propane]-dihydrochloride (AIPH), has become a research hotspot as it allows the prompt production of toxic alkyl radical (·R) upon thermal stimulation and without the need of oxygen molecules [ 7 , 8 ].…”