Smart Therapeutic Nanoplatform Based on Ti₃C₂ MXenes for Tumor-Targeted PTT/PDT/CHT at Low Temperatures

Thermal injury to surrounding normal organs resulting from hyperthermia (>50 °C) is the main challenge in photothermal therapy (PTT) of tumors. Thus, significant effort should be directed toward developing photothermal strategies that deliver robust cancer cell killing under mild hyperthermia (≤45 °C). Herein, a multimodal therapeutic nanoplatform Ti₃C₂/ICG/PDA/GA/Apt-M (TIPGA) was developed for active targeted tumor therapy at low temperatures. In the TIPGA therapeutic nanoplatform, Ti₃C₂ MXenes were employed as photothermal agents (PTAs) to produce therapeutic heat upon near-infrared light irradiation, and indocyanine green (ICG) endowed the TIPGA therapeutic nanoplatform with photodynamic therapy (PDT) performance. Furthermore, a polydopamine (PDA) membrane was coated on the therapeutic nanoplatform to improve stability and gambogic acid (GA) as an antitumor drug and heat shock protein (HSP) inhibitor was loaded onto the nanoplatform. A transmembrane glycoprotein mucin (MUC1) aptamer (Apt-M) was covalently bound to the therapeutic nanoplatform, endowing this therapeutic nanoplatform with an excellent active tumor targeting ability. The TIPGA nanoplatform exhibited efficient cellular uptake mediated by Apt-M and the intracellular release of GA triggered by glutathione (GSH). GA downregulated HSP90 expression, reducing the tumor cell resistance to thermal stresses. Encouragingly, experiments demonstrated that the TIPGA therapeutic nanoplatform could sharply accumulate in MCF-7 tumors due to its potent active targeting capability and displayed superior tumor suppressive ability through targeted PTT/PDT/CHT at low temperatures. Our findings reveal a novel approach of the Ti₃C₂-based therapeutic nanoplatform for targeted PTT/PDT/CHT at low temperatures.