Nanotheranostics:A powerful next-generation solution to tackle hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is an epidemic burden and remains highly prevalent worldwide.The significant mortality rates of HCC are largely due to the tendency of late diagnosis and the multifaceted,complex nature of treatment.Meanwhile,current therapeutic modalities such as liver resection and transplantation are only effective for resolving early-stage HCC.Hence,alt-ernative approaches are required to improve detection and enhance the efficacy of current treatment options.Nanotheranostic platforms,which utilize biocompatible nanoparticles to perform both diagnostics and targeted delivery,has been considered a potential approach for cancer management in the past few decades.Advancement of nanomaterials and biomedical engineering techniques has led to rapid expansion of the nanotheranostics field,allowing for more sensitive and specific diagnosis,real-time monitoring of drug delivery,and enhanced treatment efficacies across various malignancies.The focus of this review is on the applications of nanotheranostics for HCC.The review first explores the current epidemiology and the commonly encountered obstacles in HCC diagnosis and treatment.It then presents the current technological and functional advancements in nanotheranostic technology for cancer in general,and then specifically explores the use of nanotheranostic modalities as a promising option to address the key challenges present in HCC management.

Self-assembled multifunctional nanotheranostics against circulating tumor clusters in metastatic breast cancer

Circulating tumor clusters(CTC)disseminating from the primary tumor are responsible for secondary tumor formation where the conventional treatments such as chemotherapy and radiotherapy does not prevent the metastasis at locally advanced stage of breast cancer.In this study,a smart nanotheranostic system has been developed to track and eliminate the CTCs before it can colonize at a new site,which would reduce metastatic progression and increase the five-year survival rate of the breast cancer patients.Targeted multiresponsive(magnetic hyperthermia and pH)nanomicelles incorporated with NIR fluorescent superparamagnetic iron oxide nanoparticles were developed based on self-assembly for dual modal imaging and dual toxicity for spontaneous killing of CTCs in blood stream.A heterogenous tumor clusters model was developed to mimic the CTCs isolated from breast cancer patients.The nanotheranostic system was further evaluated for the targeting property,drug release kinetics,hyperthermia and cytotoxicity against developed CTC model in vitro.In vivo model in BALB/c mice equivalent to stageⅢandⅣhuman metastatic breast cancer was developed to evaluate the biodistribution and therapeutic efficacy of micellar nanotheranostic system.Reduced CTCs in blood stream and low distant organ metastasis after treatment with the nanotheranostic system demonstrates its potential to capture and kill the CTCs that minimize the secondary tumor formation at distant sites.

Nanotheranostics and its role in diagnosis, treatment and prevention of COVID-19

Microbe-related,especially viral-related pandemics have currently paralyzed the world and such pathogenesis is expected to rise in the upcoming years.Although tremendous efforts are being made to develop antiviral drugs,very limited progress has been made in this direction.The nanotheranostic approach can be a highly potential rescue to combat this pandemic.Nanoparticles(NPs)due to their high specificity and biofunctionalization ability could be utilized efficiently for prophylaxis,diagnosis and treatment against microbial infections.In this context,titanium oxide,silver,gold NPs,etc.have already been utilized against deadly viruses like influenza,Ebola,HIV,and HBV.The discovery of sophisticated nanovaccines is under investigation and of prime importance to induce reproducible and strong immune responses against difficult pathogens.This review focuses on highlighting the role of various nano-domain materials such as metallic NPs,magnetic NPs,and quantum dots in the biomedical applications to combat the deadly microbial infections.Further,it also discusses the nanovaccines those are already available for various microbial diseases or are in clinical trials.Finally,it gives a perspective on the various nanotechnologies presently employed for efficient diagnosis and therapy against disease causing microbial infections,and how advancement in this field can benefit the health sector remarkably.

Excipient-free porphyrin/SN-38 based nanotheranostics for drug delivery and cell imaging

Nanotheranostics with comprehensive diagnostic and therapeutic capabilities show exciting cancer treatment potentials.Here,we develop an excipient-free drug delivery system for cancer diagnosis as well as therapy,in which a near infra-red photosensitizer and a chemotherapeutic drug can be self-delivered without any carriers.The building block of the drug delivery system was synthesized by covalently conjugating four anticancer drugs(7-ethyl-10-hydroxy-camptothecin,SN-38)with a photosensitizer(porphyrin)via hydrolyzable ester linkage,which endows the drug delivery system with 100%active pharmaceutical ingredients,excellent imaging,and therapeutic functionalities.The conjugates can readily self-assemble into nanosheets(PS NSs)and remain stable for at least 20 days in aqueous solution.In PS NSs,fluorescence resonance energy transfer(FRET)dominates the fluorescence of SN-38 and enables to monitor the drug release fluorescentiy.The PS NSs also show excellent anticancer activity in vitro,due to the increased cell uptake with the synergistic effect of photodynamic therapy and chemotherapy.

Multi-responsive nanotheranostics with enhanced tumor penetration and oxygen self-producing capacities for multimodal synergistic cancer therapy

Incorporation of multiple functions into one nanoplatform can improve cancer diagnostic efficacy and enhance anti-cancer outcomes. Here, we constructed doxorubicin(DOX)-loaded silk fibroinbased nanoparticles(NPs) with surface functionalization by photosensitizer(N770). The obtained nanotheranostics(N770-DOX@NPs) had desirable particle size(157 nm) and negative surface charge(-25 m V). These NPs presented excellent oxygen-generating capacity and responded to a quadruple of stimuli(acidic solution, reactive oxygen species, glutathione, and hyperthermia). Surface functionalization of DOX@NPs with N770 could endow them with active internalization by cancerous cell lines, but not by normal cells. Furthermore, the intracellular NPs were found to be preferentially retained in mitochondria, which were also efficient for near-infrared(NIR) fluorescence imaging, photothermal imaging,and photoacoustic imaging. Meanwhile, DOX could spontaneously accumulate in the nucleus. Importantly, a mouse test group treated with N770-DOX@NPs plus NIR irradiation achieved the best tumorretardation effect among all treatment groups based on tumor-bearing mouse models and a patientderived xenograft model, demonstrating the unprecedented therapeutic effects of trimodal imagingguided mitochondrial phototherapy(photothermal therapy and photodynamic therapy) and chemotherapy.Therefore, the present study brings new insight into the exploitation of an easy-to-use, versatile, and robust nanoplatform for programmable targeting, imaging, and applying synergistic therapy to tumors.

Gastrointestinal cancers in the era of theranostics: Updates and future perspectives

Theranostics are one of the practical aspects of personalized medicine.This concept was designed to describe a material combining diagnosis,treatment and follow up of a disease.It evolved and included molecular targeting and nanotechnologies that incorporate both diagnosis and therapeutics.In this editorial,we are presenting briefly the concept and evolution of theranostics,highlighting many applications of theranostics in daily practice and discussing future perspectives and aspects of this model in gastrointestincal cancers.

Fluorescent Silicon Nanorods-Based Nanotheranostic Agents for Multimodal Imaging-Guided Photothermal Therapy

The utilization of diagnosis to guide/aid therapy procedures has shown great prospects in the era of personalized medicine along with the recognition of tumor heterogeneity and complexity.Herein,a kind of multifunctional silicon-based nanostructure,i.e.,gold nanoparticles-decorated fluorescent silicon nanorods(Au@SiNRs),is fabricated and exploited for tumor-targeted multimodal imaging-guided photothermal therapy.In particular,the prepared Au@SiNRs feature high photothermal conversion efficiency(~43.9%)and strong photothermal stability(photothermal performance stays constant after five-cycle NIR laser irradiation),making them high-performance agents for simultaneously photoacoustic and infrared thermal imaging.The Au@SiNRs are readily modified with targeting peptide ligands,enabling an enhanced tumor accumulation with a high value of^8.74%ID g?1.Taking advantages of these unique merits,the Au@SiNRs are superbly suitable for specifically ablating tumors in vivo without appreciable toxicity under the guidance of multimodal imaging.Typically,all the mice treated with the Au@SiNRs remain alive,and no distinct tumor recurrence is observed during 60-day investigation.

Engineering nanotheranostic strategies for liver cancer

The incidence and mortality of hepatocellular carcinoma have continued to increase over the last few years,and the medicine-based outlook of patients is poor.Given great ideas from the development of nanotechnology in medicine,especially the advantages in the treatments of liver cancer.Some engineering nanoparticles with active targeting,ligand modification,and passive targeting capacity achieve efficient drug delivery to tumor cells.In addition,the behavior of drug release is also applied to the drug loading nanosystem based on the tumor microenvironment.Considering clinical use of local treatment of liver cancer,in situ drug delivery of nanogels is also fully studied in orthotopic chemotherapy,radiotherapy,and ablation therapy.Furthermore,novel therapies including gene therapy,phototherapy,and immunotherapy are also applied as combined therapy for liver cancer.Engineering nonviral polymers to function as gene delivery vectors with increased efficiency and specificity,and strategies of co-delivery of therapeutic genes and drugs show great therapeutic effect against liver tumors,including drug-resistant tumors.Phototherapy is also applied in surgical procedures,chemotherapy,and immunotherapy.Combination strategies significantly enhance therapeutic effects and decrease side effects.Overall,the application of nanotechnology could bring a revolutionary change to the current treatment of liver cancer.

Biomimetic nanomedicines for precise atherosclerosis theranostics

Atherosclerosis(AS)is a leading cause of the life-threatening cardiovascular disease(CVD),creating an urgent need for efficient,biocompatible therapeutics for diagnosis and treatment.Biomimetic nanomedicines(b NMs)are moving closer to fulfilling this need,pushing back the frontier of nano-based drug delivery systems design.This review seeks to outline how these nanomedicines(NMs)might work to diagnose and treat atherosclerosis,to trace the trajectory of their development to date and in the coming years,and to provide a foundation for further discussion about atherosclerotic theranostics.

Boron difluoride formazanate dye for high-efficiency NIR-Ⅱ fluorescence imaging-guided cancer photothermal therapy

The small molecular second near-infrared(NIR-Ⅱ, 1000–1700 nm) dye-based nanotheranostics can concurrently combine deep-tissue photodiagnosis with in situ phototherapy, which occupies a vital position in the early detection and precise treatment of tumors. However, the development of small molecular NIR-Ⅱ dyes is still challenging due to the limited electron acceptors and cumbersome synthetic routes.Herein, we report a novel molecular electron acceptor, boron difluoride formazanate(BDF). Based on BDF, a new small molecular NIR-Ⅱ dye BDF1005 is designed and synthesized with strong NIR-I absorption at 768 nm and bright NIR-Ⅱ peak emission at 1034 nm. In vitro and in vivo experiments demonstrate that BDF1005-based nanotheranostics can be applied for NIR-Ⅱ fluorescence imaging-guided photothermal therapy of 4T1 tumor-bearing mice. Under 808 nm laser irradiation, tumor growth can be effectively inhibited. This work opens up a new road for the exploitation of NIR-Ⅱ small molecular dyes for cancer phototheranostics.

The Systematic Evaluation of Physicochemical and Biological Properties In Vitro and In Vivo for Natural Silk Fibroin Nanoparticles

Nanoparticle-based theranostics has served as a preferential technology for diagnosis and treatment of diseases.However,there are still massive challenges in constructing the ideal platform,which hopefully integrate various characteristics such as easy preparation,multiple utilization,and high therapeutic effect and safety into a single system.Herein,we reported a drug delivery system-based on natural silk fibroin(denoted as SF NPs),and systematically evaluated the physicochemi-cal properties,biological properties and the biosafety assessment of SF NPs.The in vitro and in vivo experimental results confirmed that SF NPs showed high stability,low blood hemolysis and the universal delivery ability of drugs.Additionally,the SF NPs could rapidly enter into cells due to its nanoscale size,and had a weak cytotoxicity against MCF-7,4T1 and L929 cells.Meanwhile,the SF NPs showed enhanced tumor permeability in a simulative model of multicellular spheroids,combined with excellent in vivo biosafety and the negligible organ injury,demonstrate that SF-based nanomedicine presents the utilization potentiality for drug delivery and may provide a new view for cancer treatment.

Doxorubicin-Ioaded Fe3O4@MoS2-PEG-2DG nanocubes as a theranostic platform for magnetic resonance imaging- guided chemo-photothermal therapy of breast cancer

Molybdenum disulfide （MoS2）, a typical transition-metal dichalcogenide, has attracted increasing attention in the field of nanomedicine because of its preeminent properties. In this study, magnetic resonance imaging （MRI）-guided chemo-photothermal therapy of human breast cancer xenograft in nude mice was demonstrated using a novel core/shell structure of Fe3O4@MoS2 nanocubes （IOMS NCs） via the integration of MoS2 （MS） film onto iron oxide （IO） nanocubes through a facile hydrothermal method. After the necessary PEGylation modification of the NCs for long-circulation purposes, such PEGylated NCs were further capped by 2-deoxy-D-glucose （2-DG）, a non-metabolizable glucose analogue to increase the accumulation of the as-prepared NCs at the tumor site, as 2-DG molecules could be particularly attractive to resource-hungry cancer cells. Such 2-DG- modified PEGylated NCs （IOMS-PEG-2DG NCs） acted as drug-carriers for doxorubicin （DOX）, which could be easily loaded within the NCs. The obtained IOMS-PEG（DOX）-2DG NCs exhibited a 3？2 relaxivity coefficient of 48.86 （mM）^-1·s^-1 and excellent photothermal performance. 24 h after intravenous injection of IOMS-PEG（DOX）-2DG NCs, the tumor site was clearly detected by enhanced T2-weighted MRI signal. Upon exposure to an NIR 808-nm laser for 5 rain at a low power density of 0.5 W·cm^-2 a marked temperature increase was noticed within the tumor site, and the tumor growth was efficiently inhibited by the chemo-photothermal effect. Therefore, our study highlights an excellent theranostic platform with great potential for targeted MRI-guided precise chemo-photothermal therapy of breast cancer.

Fluorescent traceable nanoparticles by co-self-assembly of carbon dot-drug conjugate and biodegradable hyperbranched polymer for diagnosis and therapy

Carbon dots(CDs)have attracted more interest in tumor theranostics,but they suffer from the rapid renal clearance due to small size and high hydrophilicity.To solve such problems,hydrophobic pH-triggered carbon dot-drug conjugate(CDs-Hy-DOX)with high doxorubicin(DOX)content of 48.23%were designed by covalent conjugation of DOX onto the CDs via acid-labile linkage with hydrazine(Hy)as bridge.Then the fluorescent traceable hybrid prodrug nanoparticles were fabricated via co-self-assembly with the CDs-Hy-DOX as pH-sensitive prodrug and a pH/reduction dual-triggered degradable hyperbranched polymer PEG-PO-Cy as polyethylene glycol(PEG)-based surfactant,as well as gatekeeper for pH/reduction dual-triggered DOX release.The hybrid prodrug nanoparticles with hydrodynamic diameter of 220 nm and DOX content of 22.99%were obtained with the optimized co-self-assembling condition.They could release 68.98%of DOX in the simulated tumor microenvironment within 3 days in a sustained release mode,with a premature drug leakage of 7.58%.After the acid-triggered DOX release from the CDs-Hy-DOX,which was accelerated by the pH/reduction dual-triggered degradation of the hyperbranched polymer,the strong fluorescence of CDs-Hy was recovered,demonstrating the promising potential in future tumor nanotheranostics.

Manganese-Fluorouracil Metallodrug Nanotheranostic for MRI-Correlated Drug Release and Enhanced Chemoradiotherapy

For cancer therapy,drug delivery systems are often limited by insufficient drug loading capacity,which usually results in systemic toxicity and heavy metabolic burden to excrete the carriers.Herein,we reported a“one-pot”method for constructing metal(Mn^(2+))–fluorouracil(FU)-coordinated nanotheranostics(Mn-FU)by self-assembly of FU(as bridging ligands)and Mn^(2+)(as metal nodes)through Mn–N/O coordination interactions.Importantly,owing to the effective coordination between Mn and FU,Mn-FU exhibits high drug loading efficacy(47.7 wt%),encapsulation efficacy(82.6%),and relatively large yield(1 g/pot).In acidic tumor microenvironments,efficient release of FU and Mn^(2+)is realized because of nitrogen protonation.The released FU and Mn^(2+)from Mn-FU are used for chemotherapy and turn on magnetic resonance imaging(MRI),respectively,achieving MRI-correlated drug release.After PEG modification,Mn-FU displays high tumor homing ability via enhanced permeability and retention effects and quick renal clearance owing to the disassembly in acidic biological conditions.As a result,Mn-FU substantially enhances the synergistic effects of chemoradiotherapy.Meanwhile,the systemic toxic side effects of free FU-based chemoradiotherapy were greatly reduced through this nanotheranostic.Our strategy offers a facile way to construct metallodrug nanotheranostics for efficient cancer theranostics.

Nd^(3+)-sensitized upconversion nanoparticle coated with antimony shell for bioimaging and photothermal therapy in vitro using single laser irradiation

Combining treatment and diagnosis,called theranostics,which is achieved within single nanoparticle is an ultimate goal of many studies.Herein,we developed a new nanotheranostic agent-Nd^(3+)-sensitized upconversion nanoparticles core for dual modal imaging(i.e.,upconversion luminescence imaging and magnetic resonance imaging) and antimony nanoshell for photothermal therapy(PTT).The core-shellshell upconversion nanoparticles(NaYF_(4):Yb,Er@NaYF_(4):Yb,Nd@NaGdF_(4):Nd,named as UCNP) were firstly synthesized using thermal decomposition method and then were coated by antimony shell over the surface of UCNP using simple cost and time effective new method.Furthermore,the surface of UCNP@Sb nanostructures was modified with DSPE-PEG in order to enhance the water solubility and biocompatibility.The final nanotheranostic agent,named as UCNP@Sb-PEG,exhibits very low toxicity,good biocompatibility,very good photothermal therapeutic effect,and efficient upconversion luminescence(UCL) imaging of HeLa cells under only one laser(808 nm) irradiation.The antimony shell is quenching the upconversion emission in pristine nanotheranostic agent,but interestingly,the UCL intensity of the agent recovers progressively under 808 nm laser irradiation due to light induced degradability of antimony shell.Besides,high longitudinal relaxivity(r_(1)) obtained from the experiment approves excellent potential of the nanotheranostic agent for T_(1)-weighted magnetic resonance imaging application.