RESUMO
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.
Assuntos
Hidrogéis , Cimentos de Resina , Dispositivos Eletrônicos Vestíveis , Adesivos , Animais , DNA/química , Humanos , Hidrogéis/química , Movimento (Física)RESUMO
Since adhesive hydrogels showed wide applications ranging from wearable soft materials to medical sealants, more and more attention has been paid toward the exploration of novel adhesive hydrogels. However, the difficulty in removing the residue caused by the excessive adhesive strength and sluggish degradation or nondegradation behaviors of the adhesive has always been challenging. Inspired by the multiple complementary hydrogen bond interactions in DNA, the bioinspired nucleobase (A, T, and U) monomers were first synthesized and used to tackify polyphosphoester hydrogels. The multiple hydrogen bonds and hydrophobic interactions between purine rings and pyrimidine functionalities endowed the hydrogels with excellent controllable adhesive properties. Besides this, it has been found that these nucleobase-tackified hydrogels could be easily peeled off without leaving any residue and could be totally degraded under alkaline conditions due to hydrolysis of phosphoester chains. At the same time, they also exhibited controllable biodegradation to different extents under the different pH conditions. The excellent adhesive performance, controllable biodegradation, and excellent biocompatibility showed by this nucleobase-tackified polyphosphoester adhesive hydrogel demonstrated its great potential in wound dressing, as a tissue sealant, and so on.
Assuntos
Adesivos/química , DNA/química , Hidrogéis/química , Purinas/química , Pirimidinas/química , Células 3T3 , Acrilatos/química , Animais , Materiais Biocompatíveis/química , Plásticos Biodegradáveis/química , Camundongos , Organofosfatos/químicaRESUMO
Rapid cellular uptake and efficient drug release in tumor cells are two of the major challenges for cancer therapy. Herein, we designed and synthesized a novel pH-responsive polymer-drug conjugate system poly(2-(methacryloyloxy)ethyl choline phosphate)-b-poly(2-methoxy-2-oxoethyl methacrylate-hydrazide-doxorubicin) (PCP-Dox) to overcome these two challenges simultaneously. It has been proved that PCP-Dox can be easily and rapidly internalized by various cancer cells due to the strong interaction between multivalent choline phosphate (CP) groups and cell membranes. Furthermore, Dox, linked to the polymer carrier via acid-labile hydrazone bond, can be released from carriers due to the increased acidity in lysosome/endosome (pH 5.0-5.5) after the polymer prodrug was internalized into the cancer cells. The cell viability assay demonstrated that this novel polymer prodrug has shown enhanced cytotoxicity in various cancer cells, indicating its great potential as a new drug delivery system for cancer therapy.
Assuntos
Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Neoplasias/tratamento farmacológico , Fosforilcolina/análogos & derivados , Polímeros/administração & dosagem , Ácidos Polimetacrílicos/química , Pró-Fármacos/farmacologia , Células A549 , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/química , Portadores de Fármacos , Células Hep G2 , Humanos , Concentração de Íons de Hidrogênio , Células MCF-7 , Nanopartículas/administração & dosagem , Nanopartículas/química , Fosforilcolina/química , Polímeros/química , Pró-Fármacos/químicaRESUMO
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.
Assuntos
Lipossomos , Melanoma , Animais , Linhagem Celular Tumoral , Doxorrubicina , Sistemas de Liberação de Medicamentos , Lipídeos , Melanoma/tratamento farmacológico , Camundongos , FosforilcolinaRESUMO
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.
Assuntos
Compostos Aza/química , Éteres de Coroa/química , Técnicas de Transferência de Genes , Polietilenoimina/química , Células A549 , Animais , Compostos Aza/administração & dosagem , Éteres de Coroa/administração & dosagem , Humanos , Injeções Intravenosas , Camundongos , Estrutura Molecular , Células NIH 3T3 , Nanopartículas/administração & dosagem , Nanopartículas/química , Neoplasias Experimentais , Imagem Óptica , Tamanho da Partícula , Polietilenoimina/administração & dosagem , Propriedades de SuperfícieRESUMO
Limited cellular uptake and inefficient intracellular drug release severely hamper the landscape of polymer drug nanocarriers in cancer chemotherapy. Herein, to address these urgent challenges in tumor treatment simultaneously, we integrated the multivalent choline phosphate (CP) and bioreducible linker into a single polymer chain, designed and synthesized a neoteric bioreducible polymer nanocarrier. The excellent hydrophility of these zwitterionic CP groups endowed high drug loading content and drug loading efficiency of doxorubicin to this drug delivery system (â¼22.1 wt %, â¼95.9%). Meanwhile, we found that the multivalent choline phosphate can effectively enhance the internalization efficiency of this drug-loaded nanocarrier over few seconds, and the degree of improvement depended on the CP density in a single polymer chain. In addition, after these nanocarriers entered into the tumor cells, the accelerated cleavage of bioreducible linker made it possible for more cargo escape from the delivery system to cytoplasm to exert their cytostatic effects more efficiently. The enhanced therapeutic efficacy in various cell lines indicated the great potential of this system in anticancer drug delivery applications.