Investigation Of Multifunctional Drug Carrier Based On Molybdenum Disulfide In Tumor Diagnosis And Therapy

In recent decades,tumor became one of the serious diseases that threaten the health and life.At present,the clinical treatment of cancer mainly includes surgery,chemotherapy and radiotherapy.Surgery is suitable for early primary lesions,but the treatment effect for middle and late stage of malignant tumors is often unsatisfactory.In addition,the surgical trauma to the human body is large,resulting in reduced immunity of the patient and causing postoperative complications.The development of multifunctional nanocarriers is able to improve the efficiency of both therapy and diagnosis,realizing individualized therapy.Current imaging modalities such as optical,fluorescence imaging?FL?,X-ray computed tomography?CT?and photoacoustic?PA?imaging have played increasingly important roles to guide the planning of treatment for patients.However,each single imaging modality usually has its inherent limitations,such as limited tissue penetration in optical imaging,short circulation half-lives and nonspecific distribution in CT imaging and relatively low sensitivity in PA imaging.Therefore,multimodal imaging,which is able to compensate for inherent limitations of each single imaging modality,has been an important trend in the development of new biomedical imaging instruments and contrasting agents.Molybdenum disulfide?MoS₂?is a quite interesting 2D nanomaterials transition metal dichalcogenides?TMDCs?,which has been widely studied and applied in nanoelectronics and catalysis.Encouraged by the relatively good near-infrared?NIR?absorption capability,MoS₂ have been developed in photothermal therapy?PTT?of cancers.Besides,Mo atom has strong X-ray attenuation that can be applied in theranostic applications like CT image-guided photothermal therapy.Therefore,creating MoS₂-based nanocomposites in a single system may enhance the antitumor effects.In this research,we developed two kinds of multifunctional nanocarriers based on MoS₂ nanocomposites for tumor therapy and imaging.In this study,many properties of nanocomposites were characterized and evaluated.We also assessed the therapeutic effect in vitro and in vivo.It was proved that the biodistribution and intratumoral accumulation of the nanocomposites could be real-time monitored by multi-modal imaging,guiding the tumor visualized and combined therapy.?1?In this present work,we developed X-ray computed tomography?CT?/near-infrared fluorescent?NIRF?imaging for visually guiding photothermal effect?PTT?/photodynamic effect?PDT?antitumor nanocomposites?PEG-MoS₂-Au-Ce6?by absorbing chlorin e6?Ce6?to the gold nanoparticles?AuNPs?-decorated molybdenum disulfide?PEG-MoS₂?nanosheets.Then,the NIR photosensitizer Ce6 was absorbed onto the PEG-MoS₂-Au hybrids via?–?stacking and hydrophobic interactions,where Ce6 remaining its quenched state due to the surface plasmon resonance?SPR?capacity of AuNPs as well as the coupling interaction with PEG-MoS₂ nanosheets.However,Ce6 dequenched and boosted strong NIR fluorescence signals after releasing from the surface of PEG-MoS₂-Au hybrids upon heat generation,thus performing PDT effect for anti-tumor therapy.Moreover,the PEG-MoS₂ nanosheets and Ce6 in the PEG-MoS₂-Au-Ce6 nanocomposites could be further taken advantages for CT and NIRF dual-modal imaging,respectively.In vitro NIR-triggered drug released study indicated the PEG-MoS₂-Au-Ce6 nanocomposites rapidly release drug around the tumor site under photothermal effect.Therefore,this dual-modality nanosystem enabled simultaneously precise cancer diagnosis and therapy.?2?Based on the first study,we were surprised to find that the small particle size of MoS₂ also had good photothermal effect.In addition,the small particle size of MoS₂nanoparticles was better than the water dispersibility of the MoS₂ nanoscale.However,because of the small particle size of MoS₂ nanodots,it was easy to be metabolized by the kidney,which limited the application of MoS₂ nanodots.In order to overcome these problems,we designed the MoS₂ nanodots contained in SiO₂,thereby increasing the circulation time of MoS₂ nanodots in vivo.In addition,due to the mesoporous structure of SiO₂,aluminum chloride phthalocyanine?Alpc?can be loaded in the SiO₂ channel to improve the drug loading capacity of photosensitizers.In order to avoid the premature leakage of Alpc from the Alpc-MoS₂@SiO₂ nanosystem,we designed the chitosan?CS?on the surface of the Alpc-MoS₂@SiO₂ to play a gated effect.In this experiment,we developed a novel Chitosan?CS?-controlled and Aluminum phthalocyanine chloride?Alpc?-loaded MoS₂ into a single nanoplatform?Alpc-MoS₂@SiO₂-CS?for near-infrared fluorescence?NIRF?,photoacoustic?PA?,and X-ray computed tomography?CT?multi-modality imaging-guided photothermal and photodynamic combination therapy of tumors.The MoS₂ nanodot was used as the PA/CT contrast as well as hyperthermal agent.The MoS₂@SiO₂ nanoparticles prepared by a facile one-pot approach can serve as drug-delivery vehicles to transport the NIR absorbing photosensitizer Alpc within the mesoporous cavities.Meanwhile a natural cationic polysaccharide,CS,was introduced as a gatekeeper to avoid the premature release of loaded Alpc.What's more,CS as a tumor microenvironment-responsive agent would control the release of loaded drugs to the acidic local environment in the tumor.The in vivo multimodal imaging uncovered that Alpc-MoS₂@SiO₂-CS nanocomposites showed enhanced tumor uptake and diagnosis effects after intravenous injection.More importantly,the nanocomposites exhibited an evident near-infrared induced photothermal effect in the in vitro and in vivo experiments,which remarkably improved the photodynamic therapy efficiency by accelerating the blood flow and subsequently increasing oxygen supply in the tumor.Taken together,our current work demonstrated a nanoplatform for multimodal imaging guided targeted dual-therapy,which revealed a potential strategy for tumor treatment.