Abstract
Photodynamic therapy is an effective alternative to traditional treatments due to its minimally invasive nature, negligible systemic toxicity, fewer side effects, and avoidance of drug resistance. However, it is still challenging to design photosensitizers with high singlet oxygen (1O2) quantum yields (QY) due to severe aggregation of the hydrophobic photosensitizers. Herein, we developed a discrete organoplatinum(II) metallacage using therapeutic cis-(PEt3)2Pt(OTf)2 as the building block to improve the 1O2 QY, thus achieving synergistic anticancer efficacy. The metallacage-loaded nanoparticles (MNPs) with tri-modality imaging capability allow precise diagnosis of tumor and real-time monitoring the delivery, biodistribution, and excretion of the MNPs. MNPs exhibited excellent anti-metastatic effect and superior anti-tumor performance against U87MG, drug resistant A2780CIS, and orthotopic tumor models, ablating the tumors without recurrence after a single treatment. Gene chip analyses confirmed the contribution of different therapeutic modalities to the tumor abrogation. This supramolecular platform holds potential in precise cancer theranostics.
Highlights
Photodynamic therapy is an effective alternative to traditional treatments due to its minimally invasive nature, negligible systemic toxicity, fewer side effects, and avoidance of drug resistance
Motivated by the efficient tumor uptake of these metallacage-loaded nanoparticles (MNPs) revealed by nearinfrared fluorescence imaging (NIRFI), positron emission tomography (PET), and magnetic resonance imaging (MRI), in vivo photochemotherapy exhibits superior anticancer outcomes in combating against U87MG, drug-resistant A2780CIS, and orthotopic tumor models, effectively preventing tumor recurrence and metastasis after a single treatment
The isotopic resolution of each peak was in agreement with the corresponding theoretical isotopic distribution, indicating that M possessed the expected 1:2:4 ratio of building blocks
Summary
Photodynamic therapy is an effective alternative to traditional treatments due to its minimally invasive nature, negligible systemic toxicity, fewer side effects, and avoidance of drug resistance. The large π-conjugate of planar porphyrin always suffers severe π–π stacking that leads to significant quench of the excited state, resulting in the decrease of 1O2 generation quantum yield (QY), greatly limiting their applications in PDT and raising challenges for the development of suitable pharmaceutical formulations[19,20]. It is efficient in local ablation of tumors, PDT is incapable of effectively eliminating cancers distal from the primary tumor and infiltrating cancer cells, always leading to tumor recurrence. Gene chip analyses were employed to identify the underlying biological contribution of each therapeutic modality and synergistic therapy to achieve tumor abrogation
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