Multifunctional theranostic glyconanoprobes for synergistic eradication of breast cancer

Theranostic agents hold great promise for personalized medicine by combining diagnostic and therapeutic functions. Herein, two novel multifunctional theranostic glyconanoprobes targeting breast cancer were engineered for synergistic dual chemo-gene therapy and triple chemo-gene-photothermal therapy. Upconversion nanoparticles (UCNPs) were prepared and coated with a Dox-loaded glycopeptide polymer (P-Dox) to form UCNP@P-Dox for improving stability. UCNP@MP-Dox equipped for triple therapy was prepared by combining UCNP@P-Dox with magnetic (Fe₃O₄, M) nanoparticles with photothermal properties. To regulate the expression of the anti-apoptotic Bcl-2 protein, both UCNP@P-Dox and UCNP@MP-Dox were loaded with anti-Bcl-2 siRNA. Impressive photothermal efficiency and good MRI contrast were demonstrated in preliminary evaluations. Moreover, the UCNP@P-Dox/siRNA nanoprobe for dual therapy was shown in preclinical studies to significantly increase anti-tumor efficacy. <i>In vivo</i> experiments in tumor-induced mice showed nanoprobe accumulation in tumors and enhanced antitumor efficacy with combinatorial therapy over Dox and siRNA alone. This study demonstrates the tumor-targeting capability of multifunctional theranostic glyconanoprobes, establishing chemo-gene synergy as a potent therapeutic strategy for breast cancer.