Constructing Nanoplatforms Based On Supramolecular Interactions For Tumor Theranostics

Nanodevices for multimodal tumor theranostics have attracted great attentions in the past five years.It gives the hope to achieve noninvasive tumor ablation with the combination of targeting,recognition,labeling,tracing,imaging,and therapy in a same nanometer-sized carrier.My researches focus on the understanding of supramolecular weak interactions and can mainly be divided into two stages,fabricating nanodevices based on weak interactions and exploiting weak interactions for enhanced tumor uptake.In the second chapter,Aqueous Au nanoparticles(NPs)are chosen as building blocks to construct chainlike self-assembly architectures,which greatly enhance the extinction coefficient at 808 nm.Biocompatible polypyrrole(PPy)is further adopted as the package material to coat Au NP chains,producing stable photothermal agents.Primary animal experiment proves that the current composite photothermal agents are efficient in inhibiting tumor growth under an 808 nm irradiation.To further improve the capability of tumor depression and avoid accumulation of nonbiodegradable materials,we load the cupreous complexes into biocompatible and biodegradable polymer NPs of chitosan to temporarily lower the toxicity.Based on the gradual degradation of chitosan,the release of Cu(II)exhibits chemotherapeutic behavior.Onefold chemotherapy experiments indicate the tumor inhibition rate of 93.1%.Further combining the photothermal converting capability of cupereous complexes,thermochemotherapy(TCT)achieves complete tumor ablation and no tumor recrudesce is observed in the following two months.In the thrid chapter,we use transitional metal ions doping strategy to extend the functions of polyaniline from bare photothermal conversion to magnetic resonance imaging(MRI)guided TCT.The Cu(II)doped polyaniline nanoshuttles(CuPani NSs)are capable of shortening the longitudinal relaxation(T1)of protons under magnetic fields and can help mark tumor area in T1-weighted magnetic resonance imaging.In addition,the released Cu(II)ions from CuPani NSs lead to cytotoxicity,showing the behavior of chemotherapeutic agent.Further combining the good photothermal performance of CuPani NSs,TCT achieves complete tumor ablation and protecting treated site from tumor recurrence with good safety.In the fourth chapter,the influence of weak interactions on tumor uptake is further tested in tumor models.Since Hela cells exhibit the best electrostatic attractions of CuPani NSs at cell level,a dramatically high tumor uptake rate of 8.1 %ID/g is detected in vivo.By the contrary,a lower accumulation in KB tumor is observed as 3.2 %ID/g.Further investigated in the mice bearing a double tumor model,the accumulations of NSs in KB and Hela tumors are 7.9 and 2.8 %ID/g,confirming that electrostatic attractions can actively enhance the tumor uptake.The difference of tumors in attractions with NSs could be recognized by the MRI tests and we term this targeting procedure as nonspecific tumor recognition and targeting.