In vitro development of albumin nanoparticles binding an antitumor agent
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Date
2024-07-03
Authors
Al Hasan, Mira
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Abstract
Cancer remains a highly lethal disease worldwide. Conventional cancer therapies and modern immunotherapies are non-tumor-targeted therapeutic approaches thus cannot accurately distinguish malignant cells from healthy ones, giving rise to multiple undesired side effects.
Recent advances in nanotechnology have led to the development of a variety of nanocarriers, which aim to improve the therapeutic efficacy and reduce off-target toxicity of the encapsulated anticancer agents through tumor-specific targeting. Albumin-based nanoparticles are an emerging platform for the delivery of various chemotherapeutics because of their biocompatibility, safety, and ease of surface modification for specific targeting. Nevertheless, the currently used methods for the preparation of albumin nanoparticles employ organic solvents, cross-linking agents, and harsh conditions leading to the denaturation of albumin. In this report, we developed a novel method for the preparation of human serum albumin nanoparticles (HSA NP) from albumin-based biomaterials using a top-down approach. This new method is based on green-chemistry and gentle conditions to minimize protein denaturation and potentiate targeting of endogenous albumin receptors expressed on cancer cells and blood vessels. The nanoparticles obtained using this method had a mean hydrodynamic diameter of 120 nm, polydispersity index of 0.2 and a zeta potential of -10 mV. They were stabilized by lyophilization and have shown remarkable stability (solid form and in solution). They were loaded with doxorubicin as a model anticancer drug at a loading rate of 1.5%. They had a loading efficiency of 97% and maintained their size even after loading. The biocompatibility of the unloaded nanoparticles was established in vitro using HCT116 cells. Moreover, doxorubicin loaded onto these NP had faster cytotoxic efficacy in contrast to the free drug. These results are very promising and these nanoparticles could be further developed for the delivery of anticancer drugs. Further testing in vitro is needed to determine the mechanism of internalization of these nanoparticles into cells. Furthermore, the nanoparticles loaded with doxorubicin should also be tested in vivo to look not only for improvement in cytotoxic efficacy but also reduction in adverse side effects.
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Keywords
Albumin, Nanoparticles, Cytotoxic efficacy