Abstract
Nanoparticles are widely used as theranostic agents for the treatment of various pathologies, including cancer. Among all, dendrimers-based nanoparticles represent a valid approach for drugs delivery, thanks to their controllable size and surface properties. Indeed, dendrimers can be easily loaded with different payloads and functionalized with targeting agents. Moreover, they can be used in combination with other materials such as metal nanoparticles for combinatorial therapies. Here, we present the formulation of an innovative nanostructured hybrid system composed by a metallic core and a dendrimers-based coating that is able to deliver doxorubicin specifically to cancer cells through a targeting agent. Its dual nature allows us to transport nanoparticles to our site of interest through the magnetic field and specifically increase internalization by exploiting the T7 targeting peptide. Our system can release the drug in a controlled pH-dependent way, causing more than 50% of cell death in a pancreatic cancer cell line. Finally, we show how the system was internalized inside cancer cells, highlighting a peculiar disassembly of the nanostructure at the cell surface. Indeed, only the dendrimeric portion is internalized, while the metal core remains outside. Thanks to these features, our nanosystem can be exploited for a multistage magnetic vector.
Highlights
Nanomedicine aims at developing smart devices that are able to interact selectively with pathologic cells or tissues, allowing a better signal-to-noise ratio in diagnostics and improved therapeutic index in drug delivery applications
It is known that polyamidoamine (PAMAM) dendrimers can adsorb small molecules noncovalently, releasing them in mildly acidic conditions, and this feature has already been exploited in the controlled delivery of fluorescent and therapeutic payloads [4]
We recently reported the synthesis and intracellular behavior of self-assembled systems composed of a core magnetic nanoparticle and an amphiphilic dendrimer coating [7]
Summary
Nanomedicine aims at developing smart devices that are able to interact selectively with pathologic cells or tissues, allowing a better signal-to-noise ratio in diagnostics and improved therapeutic index in drug delivery applications. Many approaches have been proposed to achieve this goal, including the use of organic-based systems, polymeric nanoparticles, and dendrimers [1]. Dendrimers are receiving increasing attention due to their controllable size and surface properties, which make them an attractive platform for drug delivery [2,3]. It is known that polyamidoamine (PAMAM) dendrimers can adsorb small molecules noncovalently, releasing them in mildly acidic conditions, and this feature has already been exploited in the controlled delivery of fluorescent and therapeutic payloads [4]. Dendrimers represent an excellent coating for metal nanoparticles, allowing the preparation of nanodevices that merge advantages of both organic and inorganic nanomaterials, such as high drug-loading capability and effective use as a contrast agent or as vector for magnetically targeted delivery.
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