Signaling Pathways and Natural Compounds in Triple-Negative Breast Cancer Cell Line

Dewi, Citra; Fristiohady, Adryan; Amalia, Riezki; Ikram, Nur Kusaira Khairul; Ibrahim, Sugeng; Muchtaridi, Muchtaridi

doi:10.3390/molecules27123661

Cited by 11 publications

(1 citation statement)

References 234 publications

(255 reference statements)

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“…The limited or unclear therapeutic target in TNBC inhibits the benefits of endocrine and targeted therapy; thus, an efficient addressing of TNBC is an unmet requisite to explore efficient therapeutic strategies. , Therapeutic approaches for TNBC are currently restricted, both due to the limited accessibility to the tumor cells and the potential systemic toxicity of the drug candidates . In recent years, signaling pathways and receptor-specific targets have been reported to be effective in TNBC patients under certain clinical conditions. − In general, for most phenotypes of TNBC, little is known, and the expression level of folate receptor α (FRα) remains unclear due to their high grade of cellular and molecular heterogeneity and due to limited evidence in the literature. , Some well-established human TNBC cell lines (e.g., SUM-149-PT, MDA-MB-231, and BT-20) used for investigation in cancer research display an unenriched but nevertheless a largely moderate to very low expression of FRα (i.e., amount of FRα on the surface: SUM-149-PT > MDA-MB-231 > BT-20). , …”

Section: Introductionmentioning

confidence: 99%

Validation of Dual-Action Chemo-Radio-Labeled Nanocarriers with High Efficacy against Triple-Negative Breast Cancer

Ilyas,

E. M. Sahnoun,

Szymura

et al. 2023

ACS Appl. Mater. Interfaces

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Identification and selectivity of molecular targets with prolonged action for difficult-to-target cancer such as triple-negative breast cancer (TNBC) represent a persisting challenge in the precision delivery of therapeutics. In the quest to target undruggable sites, this study validates the bioavailability of polydopamine-sealed mesoporous silica nanocarriers (PDA-mSiO 2 ) for in vivo drug delivery to TNBC. For controlled transport and release, the chemotherapeutic drug doxorubicin was encapsulated in mSiO 2 nanocarriers coated with a PDA layer serving as a stimuli-responsive gatekeeper or seal. For unifying targeting and treatment modalities, these nanocarriers were covalently conjugated to a macrocyclic chelator (DOTA) and folate (FA-mSiO 2. ) that enabled incorporation of radionuclides and identification of FR Alpha (FolRα) receptors present on TNBC cells. The robust chemical design of FA-and DOTA-functionalized PDA-coated mSiO 2 nanocarriers constitutes mild reaction conditions to avoid the loss of surface-bound molecules. The radiolabeling studies with the theranostic pair 68 Ga and 177 Lu showed quantitative trends for radiochemical efficacy and purity. Nanocarriers equipped with both radiolabels and affinity ligands were optimally stable when incubated with human serum for up to 120 h ( 177 Lu), demonstrating hydrophilicity with a partition coefficient (log P) of −3.29 ± 0.08. Specifically, when incubated with TNBC cells, the cells received significant FA-mSiO 2 carriers, demonstrating efficient carrier internalization and time-dependent uptake. Moreover, in vivo results visualize the retention of drug-filled carriers at the tumor sites for a long time, which holds promise for therapeutic studies. This research work demonstrates for the first time the successful dual conjugation of nanocarriers through the colocation of radionuclides and anticancer drugs that is promising for both live molecular imaging and enhanced therapeutic effect for TNBC.

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