Li Junyou

Limitations and side effects of conventional tumor therapies imperatively entail novel yet more efficacious methods against tumor. PTT, PDT and CDT have recently emerged as potent tumor therapeutic alternatives. By achieving tumor-ablation high temperature or generating highly cytotoxic ROS, these novel methods efficiently kill tumor cells while minimizing side effects, courtesy of controlled on-site functioning. Nanomaterials, which can be engineered to interact with biological systems at cellular and molecular   levels,   enable   targeted   and   precise   interventions.   Mesoporous   SiO2     (mSiO2)   coated upconversion nanoparticles (UCNPs), which convert lower-energy photons into higher-energy photons, are able to sufficiently house CDT agents CeO2 that was in situ oxidized inside mesopores. Meanwhile, functionalized mSiO2  surface enables the conjugation of TK-CUR-TPP for PDT and GRGDSP peptide chain for tumor targeting. Finally, AuNPs that were modified by light-triggered click chemistry compounds tetrazole and alkene were attached to the surface via electrostatic force to lock CeO2. After internalization by tumor cells, overexpressed ROS cleaves TK to release TPP-CUR, which resumes the negatively charged surface, causing the detachment of AuNPs and thus the release of CeO2. Upon UV light emitted by UCNP, AuNPs aggregate for remarkably enhanced PTT. Synergistically, ROS generated by CUR expedites the cleavage of TK, bolstering the more complete detachment of AuNPs and further the release of CeO2, which then generates more ROS for positive feedback and O2  for elevated PDT, forming a mutually facilitating circle. Hence, the devised UCNP@mSiO2@CeO2/AuNPs with three intertwined moieties exhibit great promises in tumor treatment in a synergistic fashion.

Audience Take Away Notes:

Our work will have a considerable impact on cancer treatment by integrating multiple sorts of therapy, including PDT, CDT, and PTT therapy. On top of the above, we designed different kinds of carriers to deliver the therapeutic agents efficiently and accurately into tumor and mitochondria, with tumor from targeting ability from GRGDSP peptide chain and mitochondria targeting ability from TPP that takes photosensitizers into mitochondria. Our work is free of commonly applied drug loading, which shows enhanced biosafety and aggregation of AuNPs provide additional photoacoustic imaging (PAI) capability. These merits of our design, in all, promise the applications of UCNPs in effective cancer treatment and encourages further explorations of nanoparticles for multifunctional cancer therapy and imaging.