Hyaluronan functionalized pH-responsive calcium carbonate nanoparticles for local treatment of breast cancer

last updated: 2023-08-02
ProjectOncoNeoTreat :: publications list
TitleHyaluronan functionalized pH-responsive calcium carbonate nanoparticles for local treatment of breast cancer
Publication TypeConference Abstract -ISI Web of Science Indexed
Year of Publication2023
AuthorsBastos F. R., Costa R. R., Soares da Costa D., Reis R. L., Pashkuleva I., and Alves N. M.

INTRODUCTION: Current radio- and chemotherapies are not efficient and many tumors remain
resistant to conventional cancer treatments. Specific properties and signaling molecules from tumor
microenvironment (TME) have been explored to increase treatment efficacy. An example is the acidic
pH of the TME that has been explored to develop stimuli responsive release systems. Herein, we
obtained biocompatible calcium carbonate (CaCO3) nanoparticles that are stable at neutral pH but
dissolve at acidic conditions and evaluated their potential as a drug carrier for local cancer treatment.
METHODS: CaCO3 nanoparticles were produced by co-precipitation of calcium chloride (CaCl2) and
sodium carbonate (Na2CO3) in the presence of ethylene glycol [1]. Rhodamine was encapsulated as a
model drug. The morphology and diameter of the nanoparticles were determined by scanning
electron microscopy and dynamic laser scattering. The particles were coated by layer-by-layer (LbL)
assembly of poly-L-lysine and hyaluronic acid (HA). The release was studied in phosphate buffered
saline at pH 6.3 and 7.4. Cultures of two breast cancer cell lines (MDA-MB-231 and SK-BR-3) and a
healthy epithelial cell line MCF10A (control) were observed under confocal laser scanning microscopy
to assess particles internalization and their effect on cell viability (live/dead staining) and metabolic
activity (Alamar Blue).
RESULTS: We obtained nanoparticles with a diameter of 560 nm and negative charge that allowed
deposition of a LbL coating containing HA - a specific ligand for CD44 receptors overexpressed in
cancer cells. The coating and the pH affected the kinetics and quantity of rhodamine release. The
coating reduced the release at pH 6.3 two-fold, and three-fold at physiological pH 7.4. Significantly
more nanoparticles were internalized after the coating by the cancer cells MDA-MB-231 and SK-BR-3,
which inhibited their metabolic activity (48h). The nanoparticles had little effect on the healthy
MCF10A cells.
DISCUSSION & CONCLUSIONS: CaCO3 particles are advantageous encapsulation systems because
therapeutics can be conveniently embedded during their production. Our results demonstrated a
higher release at the pH found in the TME and a double role of the coating in tuning the release
profile and internalization that was dependent on the expression of CD44. Keeping in mind the
possibility to tailor the size and morphology of CaCO3 nanoparticles as well as the thickness of the
coating, we suggest that this system is an excellent candidate for local stimuli responsive cancer
ACKNOWLEDGEMENTS: Portuguese Fundação para a Ciência e Tecnologia (FCT, grants
CEECIND/02842/2017, SFRH/BPD/85790/2012; project PTDC/CTM-REF/0022/2020).
REFERENCES: [1] Parakhonskiy et al, J. Nanobiotechnol. 13, 53 (2015).

JournalTissue Engineering, Part A
Conference NameTERMIS 2023 – European Chapter
Date Published2023-06-30
PublisherMary Ann Liebert, Inc.
Conference LocationManchester, United Kingdom
KeywordsCancer, Drug delivery
Peer reviewedyes

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