Multifunctional Nanocarriers For Biomolecule Delivery And Cancer Therapy

The incidence rate of cancer has been increasing year by year,accompanied by a high mortality rate,which seriously affects the life and health of people.With the development of medicine,the research on cancer has been developed rapidly.Attributing to their excellent optical,electrical and magnetic properties,nanomaterials are widely used in the field of cancer diagnosis and treatment.In this paper,biodegradable nanocarriers are constructed to deliver protein or functional nucleic acid as well as to track the biomolecule delivery and monitor the release process.The main contents are as follows: 1.Outer-Frame-Degradable Nanovehicles Featuring Near-Infrared Dual Luminescence for in Vivo Tracking of Protein Delivery in Cancer TherapyThe real-time visualization of the delivery process of therapeutic proteins in vivo is very important to cancer diagnosis and treatment.However,many proteins are non-fluorescent and cannot provide fluorescent signals for tracking their release behavior in real time.Combining with the advantages of nanomaterials,this chapter constructs a kind of degradable nanovehicles with near-infrared dual luminescence to enable highly sensitive real-time imaging of protein delivery path and release in vivo.Upconversion nanoparticles(UCNPs)as the core are coupled with fluorescent dye-doped degradable macroporous silicon(DS)layer to form core-shell nanostructure.The large pores of DS favor high payload of therapeutic protein cytochrome c(Cyt c).The further decoration of hyaluronic acid layer(HA)on the outer surface prevents premature protein leakage and imparts targeting capacity.Due to the overlap between the emission spectrum of UCNPs and the absorption spectrum of DS,the upconversion luminescence of UCNPs is well blocked by fluorescence resonance energy transfer effect.When the nanovehicles are specifically internalized by tumor cells,the intracellular hyaluronidase(HAase)degrades the outermost HA layer,leading to the slow degradation of DS,followed by protein release and signal recovery of UCNPs.The biodistribution of the nanovehicles can be visualized by tracking the fluorescence signal of doped dye at 710 nm,meanwhile,the protein release was revealed by the gradually enhanced emission signal of UCNPs at 660 nm,thereby achieving real-time imaging of protein delivery and release.In vitro and In vivo experiments collectively demonstrated the good therapeutic effect of Cyt c.This system requires neither specific binding between the protein and the carrier nor the luminescent properties of the cargo,providing a universal strategy for visualizing the translocation of various biomolecules.2.Calcium Phosphate Mineralized Porphyrin Metal-Organic Framework Nanomaterials for Combined Gene and Photodynamic TherapyMicro RNAs are the key regulatory factors for the occurrence,development and spread of cancer.Studies have shown that inhibiting the function of overexpressed oncogenic mi RNAs can suppress the proliferation of tumor cells,induce cell apoptosis and enhance the therapeutic effect of cancer.However,how to efficiently deliver mi RNAs inhibitors to organisms needs further exploration.In this chapter,PCN-224 with unsaturated metal sites on the surface is selected as the container to carry anti-21 by coordinating with the phosphate backbone of the nucleic acid.At the same time,the nanomaterial is covered with a layer of mineralized Ca P to facilitate the physiological stability,intracellular release of anti-21 and lysosomal escape of anti-21.The dispersibility of the material was improved by PEG corona.Meanwhile,the Ca P shell can effectively improve the stability of PCN-224 in the blood circulation,which accelerates the tumor accumulation of photosensitizers so as to boost the effect of photodynamic therapy.Through the introduction of Ca P,we anticipate to achieve synergistic therapeutic effect of gene and photodynamic therapy to eradicate tumor without recurrence.