Fabrication Of Photothermal Conversion Nanoparticles For Cacner Theranostics

Photothermal therapy is one of recently developed cancer therapy technologies,and can destroy cancer cells through the conversion from light energy to heat energy with the help of photothermal conversion materials to rise tissue temperature rapidly.This treatment technology has been regarded as a promsing alternative to surgery to relize tumor ablation because of the advantages of non-invasion,located ablation and easy operation.Medical imaging is used to identify and locate tumor befor therapy;medical imaging is used to monitor treatment effects during therapy;medical imaging is also used to confirm the success of treatment after therapy.Therefore,theranostic agents,the integration of imaging components and photothermal conversion agents,can reduce medication times and improve the diagnosis and treatment efficiency of cancer.Although inorganic nanomaterials such as gold,copper sulfide and carbon,and organic nanomaterials such as polyaniline,polypyrrole and porphyrin liposomes have been considered to play an important role in the diagnosis and photothermal therapy of cancer,the majority of photothermal nanomaterials in lab still face the problems of poor biocompatibility,nondegradation and complex preparation process.In this study,three kinds of novel nanoagents for cancer diagnosis and treatment were designed and prepared for the purpose of developing highly biocompatible nanomaterials,which have significant application potential for cancer diagnosis and therapy.To conquer the disadvantages of natural hydrophobic and modification requirement of carbon materials,carbon nanospheres?CNSs?with an average size of 60 nm were prepared via hydrothermal methods.Compared to carbon materials?graphene and carbon nanotube?which require the oxidation treatment,or the modification of hydrophilic molecules to enhance its dispersibility in water environment for biomedical application,CNSs have high biocompatibility,which is due to the formation of numerous hydrophilic groups during hydrothermal process.In addition,the carbonization core of CNSs inherits the strong near-infrared absorption characteristic of carbon materials,and has significant photothermal effect,and the photothermal conversion efficiency is 35.1%.With the assitance of near-infrared laser irradiation,up to 85% of cancer cells were killed through the photothermal effect;in vivo photoacoustic imaging results showed that the photoacoustic signal of tumor region at 12 h after injection was 2.5 times higher than that of preinjection,and has significant photoacoustic contrast effect.Glucosederived CNSs can be empolyed as a novel theranostic agent with high biocompatibility for photoacoustic imaging and photothermal therapy of tumors.To avoid the concerns of potential long-term toxicity in the body due to nondegradation of carbon nanospheres and other inorgnic materials,PEGylated Mn²⁺-chelated polydopamine?PMPDA?nanoparticles were developed as novel theranostic agents for simultaneous MRI imaging and photothermal ablation of cancer cells,based on intrinsic manganese-chelating properties of polydopamine nanomaterials.Polydopamine is synthesized via the polymerization of dopamine under alkaline environment,and has a similar composition and structure to human melanin,so it exhibits excellent biocompatibility in preclinical studies.The longitudinal relaxation rate reached 6.55 mM-1s-1,higher than that of commercial Gd-DTPA agent.Compared with most theranostic agents for MRI-guided phototherapy,PMPDA nanoparticles have a simple fabrication process,and do not require the introduction of external chelating agent to chelate paramagnetic metal ions,thus reducing the risk of external chelating agent.Besides,the use of Mn²⁺ for MRI signal enhancement can avoid the risk of nephrogenic systemic fibrosis.Hence,this kind of highly biocompatible theranostic agent with the combination of magnetic resonance imaging and photothermal therapy is promising.For polydopamine and other chemically synthetic materials,detailed metabolic mechanism research and long toxicity assessment are alaways required before clinical application.In this study,natural sodium humate,which are naturally formed through the biodegradation of animal and plant precursors,were developed as a promising novel theranostic agent for photoacoustic imaging and photothermal therapy.It was found that sodium humate had significant photothermal effect,and the photothermal conversion efficiency was as high as 66.2%.The results of photoacoustic imaging in vivo and in vitro showed that sodium humate had excellent photoacoustic contrast ability.After 2 h of sodium humate injection,the intensity of photoacoustic signal in the tumor area reached 2.15 times higher than that of preinjection.Upon the intratumoral injection of humic acid sodium,successful tumor ablation was achieved under laser irradiation,no recurrence of tumor within 20 days was found and the cure rate reached 100%.Subsequently,the results of the MTT cytotoxicity test,serum biochemistry and histological slice showed that sodium humate were highly biocompatible.As a new type of photohermal theranostic agent,sodium huamte has shown significant clinical application potential.