RESUMEN
Choline phosphate lipids have been designed and developed as new-generation zwitterionic nanocarriers with excellent biocompatibility and bioorthogonality to provide a more programmable performance for cancer therapy. However, there is a lack of spatiotemporal and reversible control for drug release at target tumor cells, which can lead to severe adverse effects to normal tissue and discounted treatment outcome. Here, light-inducible Lip-cRGDfk/ICG/Dox liposomes were developed for synergistic cancer therapy. ICG can effectively convert light energy into selective heating in a local environment upon laser irradiation, thus inducing thermal ablation of tumor cells, and further reversibly trigger the spatiotemporal release of anticancer drugs (Dox) at tumor cells due to the conformation transformation of CP lipids to synergistically kill tumor cells. That Lip-cRGDfk/ICG/Dox exhibited a significant improvement for breast cancer therapy inâ vitro and inâ vivo is also demonstrated, thus it can serve as an efficient platform to noninvasively and spatiotemporally control the activation of cytotoxicity at tumor cells for precision cancer therapy.
Asunto(s)
Nanopartículas , Neoplasias , Doxorrubicina , Liberación de Fármacos , Lípidos , Neoplasias/tratamiento farmacológico , FosforilcolinaRESUMEN
Hydrogels used as strain sensors often rely on splicing tapes to attach them to surfaces, which causes much inconvenience. Therefore, to develop strain sensor hydrogels that possess both good mechanical properties and self-adhesion is still a great challenge. Inspired by the multiple hydrogen bonding interactions of nucleobases in DNA, we designed and synthesized a series of hydrogels PAAm-GO-Aba/Tba/Aba+Tba comprising polyacrylamide (PAAm), graphene oxide (GO), acrylated adenine and thymine (Aba and Tba). The introduction of nucleobases helps hydrogels to adhere to various substrates through multiple hydrogen-bonding interactions. It has also been found that the adhesive strength of hydrogels with nucleobases for hogskin increased to 2.5 times that of those without nucleobases. Meanwhile, these hydrogels exhibited good dynamic mechanical and self-recovery properties. They can be directly attached to human skin as strain sensors to monitor the motions of finger, wrist, and elbow. Electrical tests indicate that they give precise real-time monitoring data and exhibit good strain sensitivity and electrical stability. This work provides a promising basis from which to explore the fabrication of tough, self-adhesive, and strain-sensitive hydrogels as strain sensors for applications in wearable devices and healthcare monitoring.
Asunto(s)
Hidrogeles , Cementos de Resina , Dispositivos Electrónicos Vestibles , Adhesivos , Animales , ADN/química , Humanos , Hidrogeles/química , Movimiento (Física)RESUMEN
Liposomes are used to deliver therapeutics in vivo because of their good biocompatibility, efficient delivery, and ability to protect the therapeutics from degradation. However, the instability of liposomes will cause the therapeutics to lose protection and become ineffective. To deliver therapeutics to the target under guard, we synthesized and used a bio-membrane mimetic choline phosphate lipid (CP-lip) to intra-crosslink liposomes to highly improve their stability. We found that when the ratio of PC-lip to CP-lip is 1 : 2, the intra-crosslinked liposome (PC-CP-lipo) showed higher stability, better biocompatibility and improved anti-protein adsorption than other common liposomes. We used doxorubicin (Dox) loaded PC-CP-lipo to treat melanoma and the tumor inhibition ratio could reach 86.3%. After the combined Dox@PC-CP-lipo treatment with PD-L1 antibody to block the immune checkpoints, the tumor suppression rate could reach 94.4%, and 60% of the mice did not suffer from tumor rechallenge. The method of using a CP-lip to intra-crosslink liposomes is applicable to all liposomes, solving the key problem of liposome disintegration, thus enhancing the protection of drugs and antibodies by liposomes in vivo.
Asunto(s)
Liposomas , Melanoma , Animales , Línea Celular Tumoral , Doxorrubicina , Sistemas de Liberación de Medicamentos , Lípidos , Melanoma/tratamiento farmacológico , Ratones , FosforilcolinaRESUMEN
To prevent tumor reproduction and metastasis, a method to modify the membranes of cancer cells was designed to suppress their vitality. A phosphatidyl choline reversed choline phosphate lipid (CP-Lip) was synthesized and modified with a PD-L1 antibody (CP-αPDL). Drug-loaded nanoparticles of CP-Lip/CP-αPDL (Dox@tCP-Lipos) could be selectively attached to melanoma cells, thus causing CP-Lip to be inserted and to interact strongly with the cell membrane, which largely reduced the fluidity and functionality of the membrane. As a result, the metabolism, reproduction, and migration of melanoma cells were proved to be weakened by CP-Lip and the tumor was 100% suppressed after treatment with Dox@tCP-Lipos.
Asunto(s)
Antineoplásicos/farmacología , Membrana Celular/química , Lípidos/química , Fosforilcolina/química , Animales , Línea Celular Tumoral , Doxorrubicina/uso terapéutico , Sistemas de Liberación de Medicamentos , Melanoma , Ratones , Neoplasias ExperimentalesRESUMEN
We proposed a method using an aza-crown ether derivative to lock a hyperbranched polyethyleneimine, which endows the PEI25k with tumor targeting ability, anti-serum ability and extended circulation in the blood meanwhile retaining the high gene complexation and high transfection efficiency. The method we proposed here simultaneously endows cationic materials with high transfection efficiency and high safety, which greatly pushed the cationic materials to be applied in in vivo gene delivery.