RESUMO
The precise and targeted delivery of therapeutic agents to the lesion sites remains a major challenge in treating brain diseases represented by ischemic stroke. Herein, we modified liposomes with mesenchymal stem cells (MSC) membrane to construct biomimetic liposomes, termed MSCsome. MSCsome (115.99 ± 4.03 nm) exhibited concentrated accumulation in the cerebral infarcted hemisphere of mice with cerebral ischemia-reperfusion injury, while showing uniform distribution in the two cerebral hemispheres of normal mice. Moreover, MSCsome exhibited high colocalization with damaged nerve cells in the infarcted hemisphere, highlighting its advantageous precise targeting capabilities over liposomes at both the tissue and cellular levels. Leveraging its superior targeting properties, MSCsome effectively delivered Dl-3-n-butylphthalide (NBP) to the injured hemisphere, making a single-dose (15 mg/kg) intravenous injection of NBP-encapsulated MSCsome facilitate the recovery of motor functions in model mice by improving the damaged microenvironment and suppressing neuroinflammation. This study underscores that the modification of the MSC membrane notably enhances the capacity of liposomes for precisely targeting the injured hemisphere, which is particularly crucial in treating cerebral ischemia-reperfusion injury.
Assuntos
Benzofuranos , Sistemas de Liberação de Medicamentos , Lipossomos , Células-Tronco Mesenquimais , Traumatismo por Reperfusão , Animais , Traumatismo por Reperfusão/terapia , Masculino , Benzofuranos/administração & dosagem , Isquemia Encefálica/terapia , Materiais Biomiméticos/química , Materiais Biomiméticos/administração & dosagem , Camundongos , Camundongos Endogâmicos C57BL , Transplante de Células-Tronco Mesenquimais/métodosRESUMO
Mesenchymal stem cell (MSC)-based therapies are flourishing. MSCs could be used as potential therapeutic agents for regenerative medicine due to their own repair function. Meanwhile, the natural predisposition toward inflammation or injury sites makes them promising carriers for targeted drug delivery. Inorganic nanoparticles (INPs) are greatly favored for their unique properties and potential applications in biomedical fields. Current research has integrated INPs with MSCs to enhance their regenerative or antitumor functions. This model also allows the in vivo fate tracking of MSCs in multiple imaging modalities, as many INPs are also excellent contrast agents. Thus, INP-integrated MSCs would be a multifunctional biologic agent with great potential. In this review, the current roles performed by the integration of INPs with MSCs, including (i) enhancing their repair and regeneration capacity via the improvement of migration, survival, paracrine, or differentiation properties, (ii) empowering tumor-killing ability through agent loaded or hyperthermia, and (iii) conferring traceability are summarized. An introduction of INP-integrated MSCs for simultaneous treatment and tracking is also included. The promising applications of INP-integrated MSCs in future treatments are emphasized and the challenges to their clinical translation are discussed.
RESUMO
Mesenchymal stem cells (MSCs) are recognized as promising drug delivery vehicles. However, the limitation of drug loading capacity and safety considerations are two obstacles to the further application of MSCs. Here, we report MSC membrane-coated mesoporous silica nanoparticles (MSN@M) that maintain the active stealth and self-positioning drug delivery abilities of MSCs and resolve issues related to MSCs-mediated drug delivery. MSN@M was established through uniformly integrating MSC membrane onto a mesoporous silica nanoparticle (MSN) core by sonication. Reduced clearance of phagocytes mediated by CD47 marker on MSC membrane was observed in vitro, which explained the only ~ 25% clearance rate of MSN@M compared with MSN in vivo within 24 h. MSN@M also showed stronger tumor targeting and penetration ability compared with MSN in HepG2 tumor bearing mice. Simultaneously, MSN@M exhibited strong capacity for drug loading and sustained drug release ability of MSN when loaded with doxorubicin (DOX), the drug loading of MSN@M increased ~ 5 folds compared with MSC membrane. In HepG2 xenograft mice, DOX-loaded MSN@M effectively inhibited the growth of tumors and decreased the side effects of treatment by decreasing the exposure of other tissues to DOX. Consequently, our MSN@M may serve as alternative vehicles for MSCs and provide more options for antitumor treatment.
Assuntos
Biomimética , Nanopartículas , Animais , Doxorrubicina , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Humanos , Camundongos , Porosidade , Dióxido de SilícioRESUMO
Understanding how systems with many semi-autonomous parts reach a desired target is a key question in biology (e.g., Drosophila larvae seeking food), engineering (e.g., driverless navigation), medicine (e.g., reliable movement for brain-damaged individuals), and socioeconomics (e.g., bottom-up goal-driven human organizations). Centralized systems perform better with better components. Here, we show, by contrast, that a decentralized entity is more efficient at reaching a target when its components are less capable. Our findings reproduce experimental results for a living organism, predict that autonomous vehicles may perform better with simpler components, offer a fresh explanation for why biological evolution jumped from decentralized to centralized design, suggest how efficient movement might be achieved despite damaged centralized function, and provide a formula predicting the optimum capability of a system's components so that it comes as close as possible to its target or goal.
Assuntos
Modelos Teóricos , AlgoritmosRESUMO
Magnetoresistance (R m) of a double-stranded (G:C) N DNA sandwiched between ferromagnetic electrodes has been studied using the transfer matrix method of the tight-binding model. A R m magnitude up to 72.5% for DNA in its natural structure is observed when the spin-orbit coupling with the helix spring geometry and a possible dephasing effect are taken into account. It can be greatly manipulated by stress or torque applied to the DNA with respect to its axis. In addition, the external voltage bias can also be used to efficiently control R m. The dependence of R m on the DNA length in a decaying oscillation form is observed.
Assuntos
DNA/química , Fenômenos Magnéticos , Modelos Moleculares , Pareamento de Bases , ElétronsRESUMO
OBJECTIVE: To report the application of reverse second dorsal metatarsal artery island flap for From May 2005 to September 2008, 5 cases with soft tissue repairing the soft tissue defect at toes. METHODS: defects at toes were treated with reverse second dorsal metatarsal artery island flaps. The flaps size ranged from 2 cm x 3 cm to 5 cm x 6 cm. RESULTS: All the 5 flaps survived completely. The patients could walk 1-2 months after operation. The patients were followed up for 5-7 months with good appearance, texture and sensation of toes. CONCLUSION: The reverse second dorsal metatarsal artery island flap has a reliable blood supply and good tissue texture. It is a practical method for repairing the soft tissue defect at toes.
Assuntos
Traumatismos do Pé/cirurgia , Transplante de Pele/métodos , Lesões dos Tecidos Moles/cirurgia , Retalhos Cirúrgicos , Adulto , Fáscia/transplante , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Retalhos Cirúrgicos/irrigação sanguínea , Dedos do Pé/lesões , Adulto JovemRESUMO
OBJECTIVE: To introduce a method by reversed ulnar fasciocutaneous flap incised form the ulnar side of the fifth metacarpal area for repairing the soft tissue defect of the fifth finger. METHODS: From May 2001 to September 2001, ten patients with the soft tissue defects of the thenar side, dorsal side or ulnar side of the fifth finger were treated with the reversed ulnar fasciocutaneous flap incised from the fifth metacarpal area. The axial line of the flap was the line from ulnar side of the head of the fifth metacarpal bone to the pisiform level. The revolving point of the flap pedicle was 0.5-1 cm near the proximal end of the metacarpal-phalangeal joint.The area of the flap was form 5.0 cm x 3.5 cm to 1.5 cm x 1.0 cm. RESULTS: All flaps of the ten cases were alive. 5-7 months followed-up show that, after operation, the flap present sensation in 6-12 mm, with soft texture and good appearances. CONCLUSIONS: The advantages of this operative method were as follows: the reversed ulnar fasciocutaneous flap of the fifth metacarpal area have reliable blood supply, it was easily dissected and with good texture. So far this kind of flap is a good choice in repairing the soft tissue of the fifth finger.