Theranostic lyotropic liquid crystalline nanostructures for selective breast cancer imaging and therapy

Herein, we report the development of theranostic lyotropic liquid crystalline nanostructures (LCN's) loaded with unique MnO nanoparticles (MNPs) for selective cancer imaging and therapy. MNPs serves as a fluorescent agent as well as a source of manganese (Mn²⁺) and enables localized oxidative stress under the hallmarks of cancer (acidosis, high H₂O₂ level). In pursuit of synergistic amplification of Mn²⁺ antitumor activity, betulinic acid (BA) is loaded in LCN's. In this investigation, nano-architecture of LCN's phase interface is established via SAXS, Cryo-TEM and Cryo-FESEM. Intriguing in vitro studies showed that the LCN's triggered hydroxyl radical production and exhibited greater selective cytotoxicity in cancer cells, ensuring the safety of normal cells. Significant tumor ablation is realized by the 96.5 % of tumor growth inhibition index of LCN's as compared to control group. Key insights into on-site drug release, local anti-cancer response, and tumor location are gained through precise guidance of fluorescent MNPs. In addition, comprehensive assessment of the safety, pharmacokinetics and tumor distribution behavior of LCN's is performed in vivo or ex vivo. This work emphasizes the promise of modulating tumor microenvironment with smart endogenous stimuli sensitive nano systems to achieve advanced comprehensive cancer nano-theranostics without any external stimulus. STATEMENT OF SIGNIFICANCE: Effective diagnosis and treatment approaches with maximum anti-cancer activity and minimal side-effects are critical to ameliorate cancer therapy. Compared to radiation, photodynamic and photothermal therapy, the specific and selective activation of tumor microenvironmental endogenous stimuli for the logical generation of cytotoxic OH^· free radicals serves as an efficient therapeutic strategy for chemodynamic-cancer treatment. In this investigation, MnO nanoparticles fulfill two needs (fluorescence-based optical imaging and a source of Mn²⁺ based chemodynamic therapy) in one unit. This approach also ensures the safety of normal cells, as the toxic OH^· free radical activity is substantially suppressed under the mild alkaline/H₂O₂ conditions in normal cell microenvironment.