A supramolecular nanoplatform for imaging-guided phototherapies via hypoxia tumour microenvironment remodeling

Abstract

A supramolecular platform was constructed for imaging-guided photodynamic and photothermal therapies by hypoxia tumour microenvironment remodeling via the inhibition of mitochondria-associated oxidative phosphorylation and combined therapeutic effects.

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“…In vivo, 38 showed almost complete tumor growth suppression compared to the PBS control after 2 weeks with 808 nm 1.0 W/cm 2 light irradiation for 5 min daily following tumor site injection. Moreover, there were negligible body weight changes in the mice and no obvious organ damage was observed, confirming the biosafety of these combinational therapies, which is essential for clinical translation …”

“…Moreover, there were negligible body weight changes in the mice and no obvious organ damage was observed, confirming the biosafety of these combinational therapies, which is essential for clinical translation. 139 Similar in mechanism to 38, synthetic high-density lipoprotein (sHDL) loaded with pyropheophorbide-a and CPT represents another actively targeted nanoscale delivery system combining photodynamic and photothermal therapy. 142 Apart from a photodynamic therapy system like 38, another notable delivery system is 39 (Figure 6), which utilizes endogenous mitochondrial ROS (mtROS) amplification for chemodynamic therapy.…”

“…The host–guest interaction between POPD and CPT-Py/Cy7-CN guests significantly reduced Cy7 aggregation and enhanced its photochemical properties, promoting ∼500% higher ROS generation compared to free Cy7 after 10 min of light irradiation by DPBF assay. Encapsulated ATO at 10 μM concentration inhibited 4T1 tumor cell mitochondrial respiration and oxygen consumption by ∼30% per Seahorse XF Cell Mito Stress Test, overcoming hypoxia limitations and further boosting in vivo PDT efficacy …”

“…Another recently reported supramolecular nanoscale delivery system, 38 (Figure 6), integrated enhanced photodynamic and photothermal therapies with CPT chemotherapy. 139 38 was achieved through host−guest interactions that co-assembled the amphiphilic polymer POPD with a pillar [5] arene base, the phototherapeutic agent Cy7-CN, the respiratory drug atovaquone (ATO), and the chemotherapeutic CPT prodrug CPT-Py with improved CPT water solubility into supramolecular nanoparticles. 139 A key feature of 38 is the incorporation of ATO to address limited PDT efficiency caused by tumor hypoxia, which can spur metastasis and recurrence.…”

“…Another recently reported supramolecular nanoscale delivery system, 38 (Figure ), integrated enhanced photodynamic and photothermal therapies with CPT chemotherapy .…”