Biological targeting has been a key concept in cancer treatment. Despite the clinical success of some biological targeting systems, significant challenges still remain. For example, there are few tumor-specific biomarkers that are expressed at sufficient high level for targeted drug delivery. Many cancers do not have tumor-specific biomarkers that are amenable for targeting. One sure example is triple-negative breast cancers (TNBCs), tumors that do not overexpress estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2. Therefore, there is great need of developing new technology that can be broadly used in the targeting of cancers, in particular those without natural biomarkers. In this study, we aim to develop azido moiety (N3)- mannose analogues that are metabolically active only in cancer cells but are not in non-cancerous cells/tissues, and the metabolism of such azido-mannose analogues lead to ?over-expression? of N3 group on cancer cell surfaces as endogenously inserted tumor biomarkers for in vitro and in vivo Click Chemistry mediated targeting. Our work will provide an entirely small-molecule-based targeting technology for many cancers that do not have established biomarkers.
We aim to incorporate the use of this new cancer targeting technology in nanomedicine and develop an effective nanotherapeutics for targeted cancer chemotherapy and immunotherapy against TNBCs. The key hypotheses to be tested in this project are (1) whether effective in vitro and in vivo cancer targeting can be achieved based on endogenous insertion of azide, a synthetic chemical functional group, as the unnatural biomarker, followed by in vitro and in vivo covalent Click Chemistry and (2) whether this new targeting technology coupled with nanomedicine can be used to treat cancers that are typically non-targetable.
Many cancers do not have tumor-specific biomarkers; targeting these cancers can be very difficult or impossible. In this study, we aim to test the hypothesis whether cancer targeting can be achieved by simply using a specially designed sugar molecule and targeted cancer therapy can be achieved via nano-chemotherapy and nano- immunotherapy coupled with the use of this small molecule mediated cancer targeting technology.