Performance Improvement And Application Of Photosensitizer Materials In Phototherapy

Cancer has seriously affected human health.Among the many clinical approaches for treating cancer,photodynamic therapy(PDT)has attracted much attention due to its advantages of non-invasiveness and spatiotemporal selectivity.Improving the optical performance of photosensitizers(PSs)is key to improving the efficacy of PDT.The short absorption wavelength of existing aggregation-induced emission(AIE)leads to limited tissue penetration depth,which is not conducive to the treatment of deep-seated tumors.Designing donor-acceptor type AIE PSs facilitates the red-shifted absorption and improves the ROS yield of PSs.However,compared with the acceptor,the available donors are limited resulting in detrimental to designing better comprehensive performance of AIE PSs.Based on this,this thesis proposes an acene donor strategy to enrich the selection of donors for AIE PSs.In addition to improving the ROS production capacity of PSs,the safety problems caused by residual PSs after PDT treatment have gradually attracted the attention of researchers.The retention of PSs in tissues will continue to cause phototoxicity under the irradiation of light to damage normal tissues and organs.At the same time,singlemode PDT or photothermal therapy(PTT)is limited by the complex growth environment of tumor cells,such as the hypoxic microenvironment and heat resistance of tumor cells,resulting in unsatisfactory therapeutic effects.To explain and solve the above problems,this thesis is divided into three chapters:(1)In Chapter 1,we introduce the development history and the working principle of PDT,the development of PSs,and the design principle of AIE PSs with high ROS yield to find the donor unit for designing high-efficiency AIE PSs.Subsequently,we focused on the safety of PDT treatment and the advantages of combined PDT and PTT.This thesis summarizes the design methods of degradable PSs in recent years,hoping to design phototherapy reagents with both safety and PDT+PTT treatment mode.(2)In Chapter 2,we developed a new kind of donor that can improve the comprehensive performance of AIE PSs by expanding the π extension of aromatic rings at the end of the triphenylamine group through acene enlargement.The absorption and fluorescence peaks of anthryl-substituted AIE PS are red-shifted by 29 nm and 42 nm;the photosensitization efficiency is enhanced by 1.16 times;the AIE factor is 86.1 and the fluorescence quantum yield is 9.9%.We also demonstrated that the anthryl-based AIE PS can image and ablate cancer cells well both in vitro and in vivo.The anthryltriphenylamine donor provides an excellent option to design donor-acceptor AIE PSs with high comprehensive performance.(3)In Chapter 3,In order to solve the side effects caused by residual PSs and the unsatisfactory effect of a single treatment mode.we demonstrated that the diketopyrrolopyrrole(DPP)derivative molecular core can be degraded by NaClO to open the ring,and it is not affected by the side substituents.Based on this,we designed and synthesized a p-DTT polymerized from DPP derivatives,which exhibited both NaClO degradability and the combined therapeutic ability of PDT and PTT.p-DTT NPs shows excellent near-infrared absorption and photostability,good photothermal conversion coefficient(η=71%),efficient ROS generation efficiency,high-resolution photoacoustic imaging capability,and can combine PDT and PTT to inhibit the growth of 4T1 cells in vivo/vitro.In addition,NaClO can turn off the PDT and PTT processes of p-DTT NPs both in solution and in cells by degrading p-DTT NPs.In solid tumors in mice,photoacoustic imaging also confirmed that NaClO can degrade p-DTT NPs.NaClO can also oxidatively break the conjugated polymer chains of p-DTT NPs to generate biomolecules with faster metabolism,further reducing side effects.