Polymeric Engineering of Nanoparticles for Highly Efficient Multifunctional Drug Delivery Systems

Abstract

Most targeting strategies of anticancer drug delivery systems (DDSs) rely on the surface functionalization of nanocarriers with specific ligands, which trigger the internalization in cancer cells via receptor-mediated endocytosis. The endocytosis implies the entrapment of DDSs in acidic vesicles (endosomes and lysosomes) and their eventual ejection by exocytosis. This process, intrinsic to eukaryotic cells, is one of the main drawbacks of DDSs because it reduces the drug bioavailability in the intracellular environment. The escape of DDSs from the acidic vesicles is, therefore, crucial to enhance the therapeutic performance at low drug dose. To this end, we developed a multifunctionalized DDS that combines high specificity towards cancer cells with endosomal escape capabilities. Doxorubicin-loaded mesoporous silica nanoparticles were functionalized with polyethylenimine, a polymer commonly used to induce endosomal rupture, and hyaluronic acid, which binds to CD44 receptors, overexpressed in cancer cells. We show irrefutable proof that the developed DDS can escape the endosomal pathway upon polymeric functionalization. Interestingly, the combination of the two polymers resulted in higher endosomal escape efficiency than the polyethylenimine coating alone. Hyaluronic acid additionally provides the system with cancer targeting capability and enzymatically controlled drug release. Thanks to this multifunctionality, the engineered DDS had cytotoxicity comparable to the pure drug whilst displaying high specificity towards cancer cells. The polymeric engineering here developed enhances the performance of DDS at low drug dose, holding great potential for anticancer therapeutic applications.

Electrophoresis of composite soft particles with differentiated core and shell permeabilities to ions and fluid flow

“…on microorganisms, nanoparticles or colloids, are interpreted on the basis of analytical equations derived by Ohshima valid for specific ranges of particle size, Debye layer thickness and shell Brinkman length. It is believed that the analytical mobility expressions developed here, valid over a larger range of conditions and applicable to a wider spectrum of core-shell particle types, will pave the way for a refined evaluation of the electro-hydrodynamic properties of colloids whose composition often involves complex mixtures of biotic and abiotic materials with diversified (bio)polymers-based surface functionalization, as required in drug delivery [74], environmental [75] and other biomedical applications [76][77]. Future developments of this work involve the derivation of electrophoretic mobility of the composite core-shell particles examined here albeit with full account of electric double layer relaxation and polarization at the Poisson-Nernst-Planck level, which requires numerical analysis of the relevant governing electro-hydrodynamic equations.…”

Thirty Years of Cancer Nanomedicine: Success, Frustration, and Hope

“…Even if the real efficacy of active targeting in cancer affected patients is still in debate, this kind of approach allowed improvement in the awareness about the molecular characteristics of different cancer types [10,72,81]. Moreover, the evidence that NCs could be entrapped inside endosomes and/or lysosomes led the scientists to study this mechanism developing NCs able to reach the cell cytosol by clever strategies, including direct fusion with the plasma membrane [59] or by performing enhanced endosomal escape [82][83][84]. The use of engineered NCs can bring other opportunities, such as the encapsulation of poorly soluble drugs [85][86][87], as well as the delivery of biologics improving their bioavailability, permeability, and stability in the biological environment [53,72].…”

Combining Nanomaterials and Developmental Pathways to Design New Treatments for Cardiac Regeneration: The Pulsing Heart of Advanced Therapies

“…Polymeric NPs have recently caught attention by virtue of their versatility and higher tunable properties, which make them extremely interesting tools for controlled drug encapsulation and release (Figures 5A,B). Indeed, their physico-chemical properties (i.e., surface charge, surface functionalities, hydrophobicity) can be finely tuned for accommodating nucleic acids, drugs and proteins to promote their efficient release inside the cells (Patil and Panyam, 2009;Fortuni et al, 2019). This large class of NPbased system include amphiphilic micelles, vesicles, dendrimers and polymersomes possessing unique structures and properties, which can be efficiently adjusted during synthesis for hosting different kind of cargos (Chandarana et al, 2018).…”