Abstract
Drug targeting of tumor cells is one of the great challenges in cancer therapy; nanoparticles based on natural polymers represent valuable tools to achieve this aim. The ability to respond to environmental signals from the pathological site (e.g., altered redox potential), together with the specific interaction with membrane receptors overexpressed on cancer cells membrane (e.g., CD44 receptors), represent the main features of actively targeted nanoparticles. In this work, redox-responsive micelle-like nanoparticles were prepared by self-assembling of a hyaluronic acid–human serum albumin conjugate containing cystamine moieties acting as a functional spacer. The conjugation procedure consisted of a reductive amination step of hyaluronic acid followed by condensation with albumin. After self-assembling, nanoparticles with a mean size of 70 nm and able to be destabilized in reducing media were obtained. Doxorubicin-loaded nanoparticles modulated drug release rate in response to different redox conditions. Finally, the viability and uptake experiments on healthy (BALB-3T3) and metastatic cancer (MDA-MB-231) cells proved the potential applicability of the proposed system as a drug vector in cancer therapy.
Highlights
Published: 26 February 2021Non-specific targeting and multi-drug resistance are the main limitations to the success of conventional chemotherapy
Nanoparticles can efficiently accumulate in the tumor site by virtue of angiogenesis and the lack of lymphatic drainage, a condition known as the enhanced permeation and retention (EPR) effect [2]
We aimed to develop a novel drug delivery system with redox-responsive and actively targeting properties for anticancer therapies
Summary
Published: 26 February 2021Non-specific targeting and multi-drug resistance are the main limitations to the success of conventional chemotherapy. The possibility to modify the physicochemical and surface properties of nanoparticles allows the amount of drug delivered to the target site to be remarkably increased For this purpose, two different approaches can be followed: (i) conjugation with ligands binding to receptors over-expressed onto the tumor cells [3]; (ii) functionalization with chemical groups able to respond to signals from tumor microenvironments [4,5]. Two different approaches can be followed: (i) conjugation with ligands binding to receptors over-expressed onto the tumor cells [3]; (ii) functionalization with chemical groups able to respond to signals from tumor microenvironments [4,5] These engineered materials, known as actively-targeted drug delivery systems, have emerged as “magic bullets” able to hit the site of disease, avoiding the side effects to other healthy organs [6]. Small molecules [7] or macromolecular compounds [8]
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