Nanoparticles based on polyferylic and polygentisic acids as new carriers of anticancer drugs
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Department of Biology, M. V. Lomonosov Moscow State University, Moscow, Russia
G. K. Skryabin Institute of Biochemistry and Physiology of Microorganisms, Russian Academy of Sciences, Pushchino, Russia
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia
Institute of Biological Instrumentation, Russian Academy of Sciences, Pushchino, Russia
Publication date: 2022-05-27
Public Health Toxicol 2022;2(Supplement Supplement 2):A9
Nanoparticles (NPs) as a tool of delivering drugs to tumor cells are considered as one of the most important options for enhancing the effectiveness of tumor treatment. Recently, the successful use of natural lignin polymers for the formation of biodegradable NPs has been shown. But the lack of certainty of the chemical structure and the limited possibility of making modifications to the chemical composition limits their use in pharmacology. We proposed to synthesize de novo polymers from phenolic monomers to be able to control polymerization and form lignin-like NPs. This makes it possible to improve such characteristics of nanosystems such as charge, stability, efficiency of penetration into human cells, and the possibility of use for targeted antitumor therapy.
This work is devoted to obtaining stable NPs based on lignin-like polymers synthesized enzymatically and chemically, and evaluating their physicochemical properties, as well as studying their penetration and cytotoxicity in vitro in tumor cell lines.
It was shown that out of the 12 studied phenolic monomers, NPs from polyferulic (pFA) and polygentisic (pGA) acids, which were synthesized using the enzyme laccase, have optimal physicochemical properties (diameter 100–300 nm, PDI lower 0.2, zeta-potential lower -30mV). The resulting NPs are stable in protein solutions and can carry hydrophobic low molecular weight compounds (Doxorubicin, Dox). When studying the internalization of NPs by tumor cell lines, a more active uptake of pFA NPs was shown. For both types of breast cancer (MDA-MB-231 and MCF-7), as well as for normal human foreskin fibroblasts (Bj-5ta), no toxicity of the empty NPs was found even at a concentration of 100 mg/mL. Loaded pFA NPs and pGA NPs have similar toxicity values to free Dox in MDA-MB-231. MCF-7 is resistant to the samples with pFA NPs, and at high concentrations of loaded Dox, NPs have a more pronounced toxic efficacy. Using 3D spheroids based on MCF-7, we have shown that, with two methods of samples incubation (with removal after 15 min and without removal, complete incubation for 48 h), NPs penetrate more efficiently and cause apoptosis.
A comparative analysis of two types of polymer NPs showed the possibility of using pFA NPs to develop new approaches to antitumor therapy, such as complex therapy using mixtures of NPs carrying different pharmacological compounds and targeted drug delivery exclusively to tumor cells.
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