A new site-specific and dual-therapeutic probe to chemically bind complementary functionalities, folic acid and macrocyclic chelator on polydopamine-capped mesoporous silica nanocarrier towards systematically tracking molecular targets and treat difficult-to-cope diseases such as triple-negative breast cancer. These mesoporous carriers demonstrate their excellent ability to encapsulate anticancer drug doxorubicin beside short- and long-lived radionuclides (Gallium-68: ⁶⁸Ga/ Leuticium-177: ¹⁷⁷Lu)] which facilitated joint biodistribution therapeutic effects study in TNBC tumour mice. The increased DOTA content and radiolabeling conditions using [⁶⁸Ga]Ga-DOTA-FA and [¹⁷⁷Lu]Lu-DOTA-FA carriers; offered quantitative excellent radiochemical efficacy and distinctive purity (> 98%). These hydrophilic carriers (partition coefficient (log P) of -3.29 ± 0.08) were optimally stable when incubated with phosphate buffer saline and human serum up to 120 h (¹⁷⁷Lu).  Using different TNBC cell lines, the active folic acid molecules on these nanocarriers allowed significant cell internalization and excellent time-dependent uptake after radiolabeling with ¹⁷⁷Lu, indicating an interaction between cells and nanocarriers. Co-administration of radiation and DOX resulted in significant cell death in all TNBC cells tested as compared to treatments with loaded or ¹⁷⁷Lu radiolabeled carriers separately which showed a therapeutic effect after extended treatment. Our data suggest that dual-functions nanocarriers has great potential in targeted delivery of radiations and drug doses for TNBC tumour treatment and points out further studies to evaluate its preclinical therapeutic efficacy.
Keywords: mesoporous silica nanoparticles; folic acid; macrocyclic chelator DOTA; radiotracers; apoptosis; targeted drug delivery; triple-negative breast cancer

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