“Petal-like” size-tunable gold wrapped immunoliposome to enhance tumor deep penetration for multimodal guided two-step strategy

Abstract

Background Breast cancer is the fastest-growing cancer among females and the second leading cause of female death. At present, targeted antibodies combined with hyperthermia locally in tumor has been identified as a potential combination therapy to combat tumors. But in fact, the uniformly deep distribution of photosensitizer in tumor sites is still an urgent problem, which limited the clinical application. We reported an HER2-modified thermosensitive liposome (immunoliposome)-assisted complex by reducing gold nanocluster on the surface (GTSL-CYC-HER2) to obtain a new type of bioplasma resonance structured carrier. The HER2 decoration on the surface enhanced targeting to the breast cancer tumor site and forming irregular, dense, "petal-like" shells of gold nanoclusters. Due to the good photothermal conversion ability under near-infrared light (NIR) irradiation, the thermosensitive liposome released the antitumor Chinese traditional medicine, cyclopamine, accompanied with the degradation of gold clusters into 3–5 nm nanoparticles which can accelerate renal metabolism of the gold clusters. With the help of cyclopamine to degrade the tumor associated matrix, this size-tunable gold wrapped immunoliposome was more likely to penetrate the deeper layers of the tumor, while the presence of gold nanoparticles makes GTSL-CYC-HER2 multimodal imaging feasible. Results The prepared GTSL-CYC-HER2 had a size of 113.5 nm and displayed excellent colloidal stability, photo-thermal conversion ability and NIR-sensitive drug release. These GTSL-CYC-HER2 were taken up selectively by cancer cells in vitro and accumulated at tumour sites in vivo. As for the in vivo experiments, compared to the other groups, under near-infrared laser irradiation, the temperature of GTSL-CYC-HER2 rises rapidly to the phase transition temperature, and released the cyclopamine locally in the tumor. Then, the released cyclopamine destroyed the stroma of the tumor tissue while killing the tumor cells, which in turn increased the penetration of the liposomes in deep tumor tissues. Moreover, the GTSL-CYC-HER2 enhanced the performance of multimodal computed tomography (CT) and photothermal (PT) imaging and enabled chemo-thermal combination therapy. Conclusions This optically controlled biodegradable plasmonic resonance structures not only improves the safety of the inorganic carrier application in vivo, but also greatly improves the anti-tumor efficiency through the visibility of in vivo CT and PT imaging, as well as chemotherapy combined with hyperthermia, and provides a synergistic treatment strategy that can broaden the conventional treatment alone. Graphic Abstract

Design and Application of Near-Infrared Nanomaterial-Liposome Hybrid Nanocarriers for Cancer Photothermal Therapy

“…Finally, gold ion is further reduced with ascorbic acid to further form a continuous GNS layer [107]. Based on the same method, Yanan Li et al reported an HER2-modified thermosensitive liposome (immunoliposome) auxiliary complex, by reducing the gold nanoclusters on the surface (GTSL-CYC-HER2) to obtain a novel type of bio-plasmonic resonance structure carrier (Figure 4B) [35]. In another study, a biodegradable liposome-AuNP carrier was designed for curcumin (CUR) delivery.…”

“…Pharmaceutics 2021, 13, x FOR PEER REVIEW 1 thermosensitive liposome (immunoliposome) auxiliary complex, by reducing the nanoclusters on the surface (GTSL-CYC-HER2) to obtain a novel type of bio-plasm resonance structure carrier (Figure 4B) [35]. In another study, a biodegradable lipo AuNP carrier was designed for curcumin (CUR) delivery.…”

“…In comparison, liposomes have good biocompatibility and easy biodegradability. Therefore, many researchers have focused on the utilization of NIRNs-liposome hybrid nanocarriers (NIRN-Lips) as they have been observed to overcome drawbacks of NIRNs [34][35][36][37].…”

“…Reprinted with permission from[95], American Chemical Society, 2020 (B) Illustration of dual-targeting GTSL-CYC-HER2 and its intracellular trafficking pathway in tumor cells. Reprinted wit permission from[35], Springer Nature, 2021.…”

Gold-Nanoparticle Hybrid Nanostructures for Multimodal Cancer Therapy

“…Another study by Li et al utilized immune-targeted GNP-coated liposomes modified with a HER-2 antibody to deliver the drug cyclopamine, a drug capable of stroma destruction and tumor cell eradication [ 104 ]. The proposed nanoformulation was reported to induce significant toxicity against tumor cells in vitro and in vivo, due to combined chemotherapy/PTT and deep tumor penetration compared with single chemotherapy or PTT treatments.…”