Novel Nanotheranostic System For Phototherapy Guided By NIR-? Fluorescence Imaging

In recent years,photodiagnosis technology has become an effective method for cancer treatment due to its excellent clinical tre effect.As a non-invasive optical diagnostic technique,near-infrared one-zone(NIR-I,650?900 nm)fluorescence imaging has been widely used in biomedical research,However,There are still various deficiencies in clinical practice,such as limited spatial resolution and poor imaging quality.Near-infrared two-zone(NIR-?,1000?1700 nm)fluorescence imaging technology has unparalleled advantages compared to NIR-I fluorescence imaging technology,such as good imaging performance,high signal-to-noise ratio,deeper penetration depth and negligible tissue autofluorescence,causing Everyone's attention.NIR-? fluorophores based on quantum dots,carbon nanotubes and rare earth materials have been designed.However,these inorganic materials have their own shortcomings,including potential toxicity and limited metabolism in vivo,which limits their clinical application.Organic materials are ingeniously designed and developed for NIR-? fluorescence imaging due to their unique chemical and optical properties,excellent biocompatibility and excellent biodegradability.Photothermal/photodynamic therapy for diagnosis and treatment by light irradiation has proved to be an effective means of cancer treatment due to its noninvasive,high efficiency and precise control.This article proposes two new ideas for NIR-? fluorescence imaging-guided phototherapy.The specific research contents are as follows:(1)Dual-mode imaging guides phototherapy / chemotherapy: a single laser triggers material NIR-? fluorescence / photoacoustic imaging,and then guides photothermal / photodynamic /chemotherapy.A new type of small molecule dye DPP-BT was designed and synthesized here.It has a strong ultraviolet absorption capacity in NIR-I,and its fluorescence emission is in NIR-?.This dye can be used not only as a contrast agent for NIR-? fluorescence imaging and photoacoustic(PA)imaging,but also as a combined therapeutic agent for photothermal(PTT)and photodynamic(PDT).By encapsulating the dye DPP-BT,the chemotherapeutic drug DOX,natural phase change materials and amphiphilic materials containing folic acid functional groups,a multifunctional photothermal nanoparticle that can be excited by a near-infrared laser is constructed.It is worth noting that under the irradiation of NIR laser,the nanoparticles generate light and heat,and DOX can be effectively released from the nanoparticles.Injecting the nanoparticles into mice with Hela tumor through the tail vein,the size and location of the tumor can be accurately observed by NIR-? fluorescence / PA dual-mode imaging.The combination of PTT / PDT / chemotherapy istriggered by NIR laser irradiation.From the perspective of in vitro and in vivo therapeutic effects,this nanoparticle shows a significant anti-tumor effect.All in all,the multifunctional nano-platform designed and constructed by this work will provide an innovative strategy for clinical photothermology.(2)NIR-? fluorescence imaging guides mitochondrial targeted phototherapy: 808 nm laser triggers material NIR-? fluorescence imaging,and then guides mitochondrial targeted photothermal/ photodynamic combined therapy.There are still many deficiencies in current photothermal therapy.Complex and long-term treatments bring unnecessary side effects to patients and increase the patients' toxicity in the body.Here,we designed and manufactured multifunctional photothermal nanoparticles based on single-component organic molecules with mitochondria as the target.After being irradiated with a single light source 808 nm laser,the nanoparticles have excellent NIR-? fluorescence signals(with a high fluorescence quantum yield of 2.2% in water),and can be used for NIR-? fluorescence imaging,NIR-? fluorescence imaging can effectively locate the tumor and monitor the treatment process in real time.In addition,under 808 nm laser irradiation,these nanoparticles also have excellent photothermal conversion efficiency(39.6%)and singlet oxygen yield(2.3%,almost 12 times the clinical NIR dye indocyanine green),both It can produce intense heat or a large amount of singlet oxygen,which eventually leads to mitochondrial dysfunction and further apoptosis.When a single light source 808 nm laser triggers high-performance NIR-? fluorescence imaging to guide mitochondrial targeted phototherapy,in vitro and in vivo studies have shown that this nano-agent shows a more significant tumor treatment effect.It is worth noting that only a single dose injection and a single 808 nm laser irradiation were used during in vivo treatment.The photothermal nanoparticles designed in this work will open up a new field for cancer treatment.