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

• DOI: 10.1021/acsami.3c10579
• Publication Date: 2023-10-13T16:22:37Z
• Authors: Shaista Ilyas; Sabri E. M. Sahnoun; Annika Szymura; Jonas Pes; Shahin Habib; Alexandru Florea; Laura Schäfer; Eva Miriam Buhl; Agnieszka Morgenroth; Pardes Habib; Felix M. Mottaghy; Sanjay Mathur
• Keywords: Nanocarriers; Triple-negative breast cancer

Identification and selectivity of molecular targets with prolonged action for difficult-to-target cancer such as triple-negative breast (TNBC) represent a persisting challenge in the precision delivery therapeutics. In quest to target undruggable sites, this study validates bioavailability polydopamine-sealed mesoporous silica nanocarriers (PDA-mSiO2) vivo drug TNBC. For controlled transport release, chemotherapeutic doxorubicin was encapsulated mSiO2 coated PDA layer serving stimuli-responsive gatekeeper or seal. unifying targeting treatment modalities, these were covalently conjugated macrocyclic chelator (DOTA) folate (FA-mSiO2.) that enabled incorporation radionuclides identification FR Alpha (FolRα) receptors present on TNBC cells. The robust chemical design FA- DOTA-functionalized PDA-coated constitutes mild reaction conditions avoid loss surface-bound molecules. radiolabeling studies theranostic pair 68Ga 177Lu showed quantitative trends radiochemical efficacy purity. Nanocarriers equipped both radiolabels affinity ligands optimally stable when incubated human serum up 120 h (177Lu), demonstrating hydrophilicity partition coefficient (log P) -3.29 ± 0.08. Specifically, cells, cells received significant FA-mSiO2 carriers, efficient carrier internalization time-dependent uptake. Moreover, results visualize retention drug-filled carriers at tumor sites long time, which holds promise therapeutic studies. This research work demonstrates first time successful dual conjugation through colocation anticancer drugs is promising live imaging enhanced effect