TY - JOUR
T1 - Validation of Dual-Action Chemo-Radio-Labeled Nanocarriers with High Efficacy against Triple-Negative Breast Cancer
AU - Ilyas, Shaista
AU - E M Sahnoun, Sabri
AU - Szymura, Annika
AU - Pes, Jonas
AU - Habib, Shahin
AU - Florea, Alexandru
AU - Schäfer, Laura
AU - Buhl, Eva Miriam
AU - Morgenroth, Agnieszka
AU - Habib, Pardes
AU - Mottaghy, Felix M
AU - Mathur, Sanjay
PY - 2023/10/13
Y1 - 2023/10/13
N2 - 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 ) for in vivo drug delivery to TNBC. For controlled transport and release, the chemotherapeutic drug doxorubicin was encapsulated in mSiO 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 ) that enabled incorporation of radionuclides and identification of FR Alpha (FolRa) receptors present on TNBC cells. The robust chemical design of FA- and DOTA-functionalized PDA-coated mSiO nanocarriers constitutes mild reaction conditions to avoid the loss of surface-bound molecules. The radiolabeling studies with the theranostic pair Ga and 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 ( Lu), demonstrating hydrophilicity with a partition coefficient (log ) of -3.29 ± 0.08. Specifically, when incubated with TNBC cells, the cells received significant FA-mSiO 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.
AB - 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 ) for in vivo drug delivery to TNBC. For controlled transport and release, the chemotherapeutic drug doxorubicin was encapsulated in mSiO 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 ) that enabled incorporation of radionuclides and identification of FR Alpha (FolRa) receptors present on TNBC cells. The robust chemical design of FA- and DOTA-functionalized PDA-coated mSiO nanocarriers constitutes mild reaction conditions to avoid the loss of surface-bound molecules. The radiolabeling studies with the theranostic pair Ga and 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 ( Lu), demonstrating hydrophilicity with a partition coefficient (log ) of -3.29 ± 0.08. Specifically, when incubated with TNBC cells, the cells received significant FA-mSiO 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.
KW - PDA-sealed mesoporous silica nanocarriers
KW - low receptor expression
KW - macrocyclic chelator
KW - radiotracers
KW - stimuli-responsive drug delivery
KW - triple-negative breast cancer
U2 - 10.1021/acsami.3c10579
DO - 10.1021/acsami.3c10579
M3 - Article
SN - 1944-8252
VL - 15
SP - 48963
EP - 48977
JO - ACS applied materials & interfaces
JF - ACS applied materials & interfaces
IS - 42
ER -