Mesoporous silica nanoparticles can be modified to perform on-demand stimuli-responsive dosing of therapeutic molecules. The silica network was loaded with iron oxide superparamagnetic nanocrystals, providing the potential to perform targeting and magnetic resonance imaging. Single-stranded DNA was immobilized onto the material surface. The complementary DNA sequence was then attached to magnetic nanoparticles. The present work demonstrates that DNA/magnetic nanoparticle conjugates are able to cap the pores of the magnetic silica particles upon hybridization of both DNA strands. Progressive double-stranded DNA melting as a result of temperature increase gave rise to uncapping and the subsequent release of a mesopore-filled model drug, fluorescein. The reversibility of DNA linkage results in an "on-off" release mechanism. Moreover, the magnetic component of the whole system allows reaching hyperthermic temperatures (42-47 °C) under an alternating magnetic field. This feature leaves open the possibility of a remotely triggered drug delivery. Furthermore, due to its capacity to increase the temperature of the surrounding media, this multifunctional device could play an important role in the development of advanced drug delivery systems for thermochemotherapy against cancer.
The treatment of complex diseases such as cancer pathologies requires the simultaneously administration of several drugs in order to improve the effectiveness of the therapy and overwhelm the defensive mechanisms of tumor cells, responsible of the apparition of multidrug resistance (MDR). In this manuscript, a novel nanodevice able to perform remotely controlled release of small molecules and proteins in response to an alternating magnetic field has been presented. This device is based on mesoporous silica nanoparticles with iron oxide nanocrystals encapsulated inside the silica matrix and decorated on the surface with a thermoresponsive copolymer of poly(ethyleneimine)-b-poly(N-isopropylacrylamide) (PEI/ NIPAM). The polymer structure has been designed with a double purpose, to act as temperature-responsive gatekeeper for the drugs trapped inside the silica matrix and, on the other hand, to retain proteins into the polymer shell by electrostatic or hydrogen bonds interactions. The nanocarrier traps the different cargos at low temperatures (20 °C) and releases the retained molecules when the temperature exceeds 35−40 °C following different kinetics. The ability to remotely trigger the release of different therapeutic agents in a controlled manner in response to a nontoxic and highly penetrating external stimulus as alternating magnetic field, along with the synergic effect associated to hyperthermia and chemotherapy, and the possibility to use this nanocarrier as contrast agent in magnetic resonance imagining (MRI) convert this nanodevice in an excellent promising candidate for further studies for oncology therapy.
MSNPs are promising nanocarriers to efficiently transport and site-specifically deliver highly toxic drugs, such as chemotherapeutic agents for cancer treatment. However, there are certain issues that should be overcome to improve the suitability of MSNPs for clinical applications. Increasing the penetration capability of MSNPs within tumour tissues, providing them of appropriate colloidal stability in physiological fluids and ensuring that their active targeting capability and stimuli-responsive performance are preserved in complex biological media are of foremost significance. Few in vivo evaluation tests of MSNPs have been reported and much research effort into this field is mandatory to be able to move from bench to bedside.
A new method for the synthesis of beta(3)-amino acids is presented. Phthalimide protected allylic amines are oxidized under Wacker conditions selectively to aldehydes using PdCl(2) and CuCl or Pd(MeCN)(2)Cl(NO(2)) and CuCl(2) as complementary catalyst systems. The aldehydes are produced in excellent yields and exhibit a large substrate scope. Beta-amino acids and alcohols are synthesized by oxidation or reduction and subsequent deprotection.
An innovative self-propelled nanodevice able to perform motion, cargo transport, and target recognition is presented. The system is based on a mesoporous motor particle, which is asymmetrically functionalized by the attachment of single-stranded DNA onto one of its faces, while catalase is immobilized on the other face. This enzyme allows catalytic decomposition of hydrogen peroxide to oxygen and water, giving rise to the driving force for the motion of the whole system. Moreover the motor particles are able to capture and transport cargo particles functionalized with a noncomplementary single-stranded DNA molecule, only if a specific oligonucleotide sequence is present in the media. Functionalization with characteristic oligonucleotide sequences in the system implies a potential for further developments for lab-on-chip devices with applications in biomedical applications.
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