Multifunctional Theranostic Nanoplatform Research Articles

A General In Situ Growth Strategy of Designing Theranostic NaLnF4@Cu2−xS Nanoplatform for In Vivo NIR‐II Optical Imaging Beyond 1500 nm and Photothermal Therapy

AbstractTheranostic nanoprobes with a combination of highly sensitive optical bioimaging and photothermal therapy (PTT) are considered advanced tools for improving the detection precision and the imaging‐guided hyperthermal therapy efficacy against tumor in the biomedical area. Compared with the traditional visible/first near‐infrared (NIR‐I, 650–900 nm) light‐emitting optical probe, a nanoprobe capable of generating the second near‐infrared (NIR‐II, 1000–1700 nm) emission is emerging as the next‐generation optical imaging technique with high‐sensitivity, and high spatial/time resolution owing to its remarkably reduced photon scattering losses. However, a multifunctional theranostic nanoplatform incorporated with the new advanced NIR‐II optical imaging and PTT has not yet been explored. Herein, a general strategy for designing theranostic nanoplatforms by integrating NIR‐II optical bioimaging with photothermal functions via in situ growth of Cu2−xS quantum dots on the lanthanide nanorods is demonstrated. The as‐prepared NaLnF4:Yb/Er@Cu2−xS hybrid nanoprobes with a core‐satellite structure present excellent NIR‐II emission centered at 1525 nm, highly stable photothermal effects and good biocompatibility. These designed theranostic nanoprobes are utilized for NIR‐II optical imaging, small tumor detection (5 mm in diameter), and PTT. More importantly, non‐invasive brain vessel visualization with high spatial resolution (44.2 µm) through scalp and skull without craniotomy is demonstrated. Therefore, these results pave the way to designing new multifunction theranostic nanoplatforms for highly sensitive NIR‐II optical‐guided tumor detection, non‐invasive blood vessel imaging, and PTT.

Iron oxide-gold core-shell nano-theranostic for magnetically targeted photothermal therapy under magnetic resonance imaging guidance.

Recent efforts in the area of photothermal therapy (PTT) follow two important aims: (i) selective targeting of plasmonic nanoparticles to the tumor and (ii) real-time guidance of PTT operation through employing multimodal imaging modalities. In the present study, we utilized a multifunctional theranostic nanoplatform constructed from iron (III) oxide-gold (Fe2O3@Au) core-shell nanoparticles to fulfill these aims. The Au shell exhibits surface plasmon resonance, a property that is exploited to realize PTT. The magnetic core enables Fe2O3@Au to be employed as a magnetic resonance imaging (MRI) contrast agent. Furthermore, the magnetic core has the potential to establish a magnetic drug targeting strategy through which Fe2O3@Au can be directed to the tumor site by means of magnetic field. To test these potentials, Balb/c mice bearing CT26 colorectal tumor model were intravenously injected with Fe2O3@Au. Immediately after injection, a magnet was placed on the tumor site for 3h to concentrate nanoparticles, followed by the near infrared (NIR) laser irradiation. MRI study confirmed the accumulation of nanoparticles within the tumor due to T2 enhancement capability of Fe2O3@Au. The in vivo thermometry results demonstrated that the tumors in magnetic targeting group had a significantly higher temperature elevation rate upon NIR irradiation than non-targeted group (~ 12°C vs. 8.5°C). The in vivo antitumor assessment revealed that systemic injection of Fe2O3@Au in combination with magnetic targeting and NIR irradiation resulted in complete remission of tumor growth. Therefore, Fe2O3@Au can establish a targeted PTT strategy for efficient eradication of tumor cells under the guidance of MRI.

Multifunctional Thermosensitive Liposomes Based on Natural Phase-Change Material: Near-Infrared Light-Triggered Drug Release and Multimodal Imaging-Guided Cancer Combination Therapy.

Multifunctional theranostic nanoplatforms (NPs) in response to environment stimulations for on-demand drug release are highly desirable. Herein, the near-infrared (NIR)-absorbing dye, indocyanine green (ICG), and the antitumor drug, doxorubicin (DOX), were efficiently coencapsulated into the thermosensitive liposomes based on natural phase-change material. Folate and conjugated gadolinium (Gd) chelate-modified liposome shells enhance active targeting and magnetic resonance performance of the NPs while maintaining the size of the NPs. The ICG/DOX-loaded and gadolinium chelate conjugated temperature-sensitive liposome nanoplatforms (ID@TSL-Gd NPs) exhibited NIR-triggered drug release and prominent chemo-, photothermal, and photodynamic therapy properties. With the coencapsulated ICG, DOX, and the conjugated gadolinium chelates, the ID@TSL-Gd NPs can be used for triple-modal imaging (fluorescence/photoacoustic/magnetic resonance imaging)-guided combination tumor therapy (chemotherapy, photothermotherapy, and photodynamic therapy). After tail vein injection, the ID@TSL-Gd NPs accumulated effectively in subcutaneous HeLa tumor of mice. The tumor was effectively suppressed by accurate imaging-guided NIR-triggered phototherapy and chemotherapy, and no tumor regression and side effects were observed. In summary, the prepared ID@TSL-Gd NPs achieved multimodal imaging-guided cancer combination therapy, providing a promising platform for improving diagnosis and treatment of cancer.

A versatile theranostic nanoplatform based on mesoporous silica

A versatile of mesoporous silica is designed and operated, including ion doping, surface modify and pore adsorption, based on aqueous well-dispersed. Thus, a multifunctional theranostic nanoplatform is obtained through endowing some functional materials. Detailedly, Gd ions is introduced to mesoporous silica (GM nanoparticles) via a co-assemble process, which is used as prime carrier with MRI. Furthermore, the surface graft of hyaluronic acid (HA) molecule makes contribution to lymph system-targeted delivery (GMH nanoparticles). Additionally, the introduction of functional molecules including Iopamidol (IGMH nanoparticles) and DOX (DGMH nanoparticles) could combine the diagnosis and therapy with CT and sustained drug release. We present evidence that the IGMH and DGMH nanoparticles are highly targeted to lymph system in vitro and in vivo, and highlight CT and MR imaging of IGMH nanoparticles in lymph system, and chemotherapy and MR imaging of DGMH nanoparticles in lymph cancer. Our results provide a new universal manufacture for mesoporous silica to obtain a multifunctional theranostic nanoplatform, has great potential for use in biological applications.

Endogenous oxygen generating multifunctional theranostic nanoplatform for enhanced photodynamic-photothermal therapy and multimodal imaging.

Phototherapy, including photothermal therapy (PTT) and photodynamic therapy (PDT), has been considered as a noninvasive option for cancer therapy. However, insufficient penetration depth, tumor hypoxia, and a single treatment method severely limit the effectiveness of treatment.Methods: In this study, a multifunctional theranostic nanoplatform has been fabricated based on Au/Ag-MnO2 hollow nanospheres (AAM HNSs). The Au/Ag alloy HNSs were first synthesized by galvanic replacement reaction and then the MnO2 nanoparticles were deposited on the Au/Ag alloy HNSs by the reaction between Ag and permanganate (KMnO4), finally obtained the AAM HNSs. Then, SH-PEG was modified on the surface of AAM HNSs by the interaction of sulfhydryl and Au/Ag alloy, which improved the dispersibility and biocompatibility of the HNS. Next, the PDT photosensitizer Ce6 was loaded into AAM HNSs, benefiting from the hollow interior of the structure, and the AAM-Ce6 HNSs were obtained.Results: The AAM HNSs exhibit broad absorption at the near infrared (NIR) biological window and remarkable photothermal conversion ability in the NIR-II window. The MnO2 nanoparticles can catalyze endogenous H2O2 to generate O2 and enhance the therapeutic effect of PDT on tumor tissue. Simultaneously, MnO2 nanoparticles intelligently respond to the tumor microenvironment and degrade to release massive Mn2+ ions, which introduce magnetic resonance imaging (MRI) properties. When AAM-Ce6 HNSs are loaded with Ce6, the AAM-Ce6 HNSs can be used for triple-modal imaging (fluorescence/photoacoustic/magnetic resonance imaging, FL/PAI/MRI) guided combination tumor phototherapy (PTT/PDT).Conclusion: This multifunctional nanoplatform shows synergistic therapeutic efficacy better than any single therapy by achieving multimodal imaging guided cancer combination phototherapy, which are promising for the diagnosis and treatment of cancer.

Chromium-Doped Zinc Gallogermanate@Zeolitic Imidazolate Framework-8: A Multifunctional Nanoplatform for Rechargeable In Vivo Persistent Luminescence Imaging and pH-Responsive Drug Release.

Multifunctional theranostic nanoplatforms greatly improve the accuracy and effectiveness in tumor treatments. Much effort has been made in developing advanced optical imaging-based tumor theranostic nanoplatforms. However, autofluorescence and irradiation damage of the conventional fluorescence imaging technologies as well as unsatisfied curative effects of the nanoplatforms remain great challenges against their wide applications. Herein, we constructed a novel core-shell multifunctional nanoplatform, that is, chromium-doped zinc gallogermanate (ZGGO) near-infrared (NIR) persistent luminescent nanoparticles (PLNPs) as a core and zeolitic imidazolate framework-8 (ZIF-8) as a shell (namely ZGGO@ZIF-8). The ZGGO@ZIF-8 nanoplatform possessed dual functionalities of the autofluorescence-free NIR PersL imaging as well as the pH-responsive drug delivery, thus it has high potential in tumor theranostics. Notably, the loading content of doxorubicin (DOX) in ZGGO@ZIF-8 (LC = 93.2%) was quite high, and the drug release of DOX-loaded ZGGO@ZIF-8 was accelerated in an acidic microenvironment such as tumor cells. The ZGGO@ZIF-8 opens up a new material system in the combination of PLNPs with metal-organic frameworks and may offer new opportunities for the development of advanced multifunctional nanoplatforms for tumor theranostics, chemical sensing, and optical information storage.

Iron-gold (Fe2O3@Au) core-shell nano-theranostic for magnetically targeted photothermal therapy under magnetic resonance imaging guidance

Introduction: Photothermal therapy (PTT) is a nanotechnology-assisted cancer hyperthermia approach in which the interaction between laser light and plasmonic nanoparticles generates a localized heating for thermoablation of the tumor. Recent efforts in the area of PTT follow two important aims: (i) exploitation of targeting strategies for preferential accumulation of plasmonic nanoparticles within the tumor and (ii) enabling real-time guidance of PTT operation through employing multimodal imaging modalities. Materials and Methods: In the present study, we utilized a multifunctional theranostic nanoplatform constructed from a magnetic core and Au shell (Fe2O3@Au) in order to fulfill these aims. The Au shell exhibits surface plasmon resonance, a property that is exploited to realize PTT. The magnetic core enables Fe2O3@Au to be used as magnetic resonance imaging (MRI) contrast agent. Furthermore, the magnetic core can also be used to achieve a magnetic drug targeting strategy through which Fe2O3@Au would be concentrated in the tumor site by means of magnetic field. Balb/c mice bearing CT26 colorectal tumor model were intraperitoneally injected with Fe2O3@Au. Immediately after injection, a magnet (magnetic field strength of 0.4 Tesla) was placed on the tumor site for 6 hours in order to concentrate Fe2O3@Au, and thereafter the tumors were irradiated with the near infrared (NIR) laser source (808 nm; 2 W/cm2; 3 min). This experiment was conducted for three sessions. Results: MRI confirmed the accumulation of nanoparticles within the tumor due to T2 enhancement capability of Fe2O3@Au. The temperature of the tumors without magnetic targeting was increased by ~7°C after NIR irradiation, whereas the tumors in magnetic targeting group showed a temperature rise of ~12°C. Conclusion: The in vivo antitumor assessment revealed that intraperitoneal injection of Fe2O3@Au nanoparticles and their targeting via magnetic field toward the tumor followed by NIR irradiation remarkably inhibited tumor growth and induced extensive necrosis. Therefore, Fe2O3@Au can establish a targeted MRI-guided PTT strategy.

A dual-targeted hyaluronic acid-gold nanorod platform with triple-stimuli responsiveness for photodynamic/photothermal therapy of breast cancer

Multi-stimuli-responsive theranostic nanoplatform integrating functions of both imaging and multimodal therapeutics holds great promise for improving diagnosis and therapeutic efficacy. In this study, we reported a pH, glutathione (GSH) and hyaluronidase (HAase) triple-responsive nanoplatform for HER2 and CD44 dual-targeted and fluorescence imaging-guided PDT/PTT dual-therapy against HER2-overexpressed breast cancer. The nanoplatform was fabricated by functionalizing gold nanorods (GNRs) with hyaluronic acid (HA) bearing pendant hydrazide and thiol groups via Au-S bonds, and subsequently chemically conjugating 5-aminolevulinic acid (ALA), Cy7.5 and anti-HER2 antibody onto HA moiety for PDT, fluorescence imaging and active targeting, respectively. The resulting versatile nanoplatform GNR-HA−ALA/Cy7.5-HER2 had uniform sizes, favorable dispersibility, as well as pH, GSH and HAase triple-responsive drug release manner. In vitro studies demonstrated that HER2 and CD44 receptor-mediated dual-targeting strategy could significantly enhance the cellular uptake of GNR-HA−ALA/Cy7.5-HER2. Under near-infrared (NIR) irradiation, MCF-7 cells could efficiently generate reactive oxygen species (ROS) and heat, and be more efficiently killed by a combination of PDT and PTT as compared with individual therapy. Pharmacokinetic and biodistribution studies showed that the nanoplatform possessed a circulation half-life of 1.9 h and could be specifically delivered to tumor tissues with an accumulation ratio of 12.8%. Upon the fluorescence imaging-guided PDT/PTT treatments, the tumors were completely eliminated without obvious side effects. The results suggest that the GNR-HA−ALA/Cy7.5-HER2 holds great potential for breast cancer therapy. Statement of significanceA combination of photodynamic therapy (PDT) and photothermal therapy (PTT) is emerging as a promising cancer treatment strategy. However, its therapeutic efficacy is compromised by the nonspecific delivery and unintended release of photo-responsive agents. Herein, we developed a multifunctional theranostic nanoplatform GNR-HA−ALA/Cy7.5-HER2 with pH, glutathione and hyaluronidase triple-responsive drug release for HER2 and CD44 dual-targeted and fluorescence imaging-guided PDT/PTT therapy against breast cancer. We demonstrated that HER2 and CD44 receptors-mediated dual-targeting strategy significantly enhanced the cellular uptake of GNR-HA−ALA/Cy7.5-HER2. We also demonstrated that the combined PDT/PTT treatment had significantly superior antitumor effect than PDT or PTT alone both in vitro and in vivo. Therefore, GNR-HA−ALA/Cy7.5-HER2 could serve as a promising nanoplatform for HER2-positive breast cancer therapy.

Dendrimer-Stabilized Gold Nanoflowers Embedded with Ultrasmall Iron Oxide Nanoparticles for Multimode Imaging-Guided Combination Therapy of Tumors.

Development of multifunctional theranostic nanoplatforms with improved diagnostic sensitivity and therapeutic efficiency of tumors still remains a great challenge. A unique multifunctional theranostic nanoplatform based on generation 5 (G5) poly(amidoamine) dendrimer–stabilized gold nanoflowers (NFs) embedded with ultrasmall iron oxide (USIO) nanoparticles (NPs) for multimode T 1‐weighted magnetic resonance (MR)/computed tomography (CT)/photoacoustic (PA) imaging–guided combination photothermal therapy (PTT) and radiotherapy (RT) of tumors is reported here. G5 dendrimer–stabilized Au NPs and citric acid–stabilized USIO NPs are separately prepared, the two particles under a certain Fe/Au molar ratio are mixed to form complexes, the complexes are exposed to Au growth solution to form NFs via a seed–mediated manner, and the remaining dendrimer terminal amines are acetylated. The formed dendrimer‐stabilized Fe3O4/Au NFs (for short, Fe3O4/Au DSNFs) have a mean diameter of 99.8 nm, display good colloidal stability and cytocompatibility, and exhibit a near‐infrared absorption feature. The unique structure and composition of the Fe3O4/Au DSNFs endows them with a high r 1 relaxivity (3.22 mM−1 s−1) and photothermal conversion efficiency (82.7%), affording their uses as a theranostic nanoplatform for multimode MR/CT/PA imaging and combination PTT/RT of tumors with improved therapeutic efficacy, which is important for translational nanomedicine applications.

Amphiphilic redox-sensitive NIR BODIPY nanoparticles for dual-mode imaging and photothermal therapy

Theranostics, integrating tumor treatment and diagnosis concurrently, has become an emerging and meaningful strategy in cancer therapy. In this work, an amphiphilic redox-sensitive near-infrared (NIR) BODIPY dye, which could be formed into nanoparticles (PEG-SS-BDP NPs) by self-assembly, was synthesized and possessed good capability of photothermal therapy (PTT), near-infrared fluorescence (NIRF) imaging, photoacoustic (PA) imaging and drug loading. The stable nanoparticles could be dissociated to turn on NIRF due to the rift of embedded disulfide bonds by glutathione (GSH). The enhanced fluorescence in vitro could be observed via confocal laser scanning microscopy (CLSM) after adding GSH, confirming the redox-sensitivity of disulfide bonds. NIRF and PA imaging demonstrated active accumulation in tumor and good imaging effect. At last, PEG-SS-BDP NPs could significantly suppress tumor growth in vivo upon irradiation. The amphiphilic redox-sensitive BODIPY nanoparticles provide a promising design strategy to formulate multifunctional stimuli-responsive theranostic nanoplatforms.

An efficient tumor-inducible nanotheranostics for magnetic resonance imaging and enhanced photodynamic therapy

Though imaging guided photodynamic therapy (PDT) has emerged as a promising cancer therapy, how to enhance the PDT efficiency is still a research hotpot due to the tumor hypoxia and insufficient dosage of photosensitizers in the tumor site. Herein, a multifunctional theranostic nanoplatform was rationally constructed by nanoscale metal organic frameworks (NMOFs), bovine serum albumin (BSA), sulfadiazines (SDs), and MnO2. Porphyrin as organic ligands involved in the formation of NMOFs, which could allow more photosensitizers in one system. BSA as ideal carrier endows the nanoplatform with low toxicity and long circulation. SDs was introduced to provide actively targeting for the over-expressed carbonic anhydrase IX (CA IX) in tumor cells. More importantly, this nanoplatform can overcome the hypoxic microenvironment via down-regulating CA IX and catalyzing H2O2 to generate O2, resulting in significantly enhanced PDT effect, which was demonstrated by the photocytotoxicity against 4T1 cells and the decreased tumor volume. In addition, in vitro/vivo T1-weighted MRI results showed that the nanoplatform could be served as positive MRI contrast agent with a higher longitudinal relaxivity value (r1) at 6.09 mM−1 s−1 than that of clinical clinical contrast agent (Gd-DTPA, r1 = 4.33 mM−1 s−1). Such theranostic nanoplatform integrates multifunctional contents into one system and thereby provides a new strategy for targeted tumor therapy.

Oridonin-loaded and GPC1-targeted gold nanoparticles for multimodal imaging and therapy in pancreatic cancer

PurposeEarly diagnosis and therapy are critical to improve the prognosis of patients with pancreatic cancer. However, conventional imaging does not significantly increase the capability to detect early stage disease. In this study, we developed a multifunctional theranostic nanoplatform for accurate diagnosis and effective treatment of pancreatic cancer.MethodsWe developed a theranostic nanoparticle (NP) based on gold nanocages (AuNCs) modified with hyaluronic acid (HA) and conjugated with anti-Glypican-1 (anti-GPC1) antibody, oridonin (ORI), gadolinium (Gd), and Cy7 dye. We assessed the characteristics of GPC1-Gd-ORI@HAuNCs-Cy7 NPs (ORI-GPC1-NPs) including morphology, hydrodynamic size, stability, and surface chemicals. We measured the drug loading and release efficiency in vitro. Near-infrared fluorescence (NIRF)/magnetic resonance imaging (MRI) and therapeutic capabilities were tested in vitro and in vivo.ResultsORI-GPC1-NPs demonstrated long-time stability and fluorescent/MRI properties. Bio-transmission electron microscopy (bio-TEM) imaging showed that ORI-GPC1-NPs were endocytosed into PANC-1 and BXPC-3 (overexpression GPC1) but not in 293 T cells (GPC1- negative). Compared with ORI and ORI-NPs, ORI-GPC1-NPs significantly inhibited the viability and enhanced the apoptosis of pancreatic cancer cells in vitro. Moreover, blood tests suggested that ORI-GPC1-NPs showed negligible toxicity. In vivo studies showed that ORI-GPC1-NPs enabled multimodal imaging and targeted therapy in pancreatic tumor xenografted mice.ConclusionORI-GPC1-NP is a promising theranostic platform for the simultaneous diagnosis and effective treatment of pancreatic cancer.

Self-Assembled Minimalist Multifunctional Theranostic Nanoplatform for Magnetic Resonance Imaging-Guided Tumor Photodynamic Therapy.

Minimalist multifunctional platforms for delivering diagnostic and therapeutic agents effectively and safely into tumor sites are highly desired in nanomedicine. Herein, we describe the fabrication of a supramolecular nanoplatform via the amphiphilic amino acid (9-fluorenylmethyloxycarbonyl-l-leucine, Fmoc-l-L)-modulated self-assembly of a magnetic resonance imaging (MRI) contrast agent (ionic manganese, Mn2+) and photosensitive drug (chlorin e6, Ce6). Coordination drives the coassembly of Fmoc-l-L and Mn2+ to generate a nanoscale supramolecular network to adaptively encapsulate Ce6. The obtained biometal-organic nanoparticles exhibit a high drug loading capability, inherent good biocompatibility, robust stability, and smart disassembly in response to glutathione (GSH). The cooperative assembly of the multiple components is synchronously dynamic in nature and enables enhanced photodynamic therapy (PDT) to damage tumor cells and tissue by efficiently delivering the photosensitizer and improving the reductive tumor microenvironment via the competitive coordination of GSH with Mn2+. The antitumor effect can also be monitored and evaluated in vivo by MRI through the long-term intracellular biochelation of Mn2+. Therefore, this work presents a one-pot and robust method for the self-assembly of a multifunctional theranostic nanoplatform capable of MRI-guided PDT starting from minimalist biological building blocks.

Paclitaxel-Induced Ultrasmall Gallic Acid-Fe@BSA Self-Assembly with Enhanced MRI Performance and Tumor Accumulation for Cancer Theranostics.

Ultrasmall nanoparticles have attracted great attention because of their efficient renal clearance. However, their bioapplication is still severely hampered by the poor performance derived from low tumor accumulation. Here, a large, self-assembled nanoparticle was designed for cancer theranostics and used with paclitaxel (PTX) to assemble bovine serum albumin-coated ultrasmall gallic acid-Fe(III) (GA-Fe@BSA-PTX) nanoparticles by the hydrophobic effect. The GA-Fe@BSA-PTX self-assembled nanoparticles featured appropriate size (∼115 nm), high water dispersity and stability, and low cell toxicity. Importantly, the magnetic resonance imaging performance and tumor accumulation of GA-Fe@BSA-PTX self-assembled nanoparticles were much better than those of the ultrasmall GA-Fe@BSA nanoparticles. Furthermore, the GA-Fe@BSA-PTX self-assembled nanoparticles exhibited an excellent therapeutic effect on tumors, owing to the combined chemo- and photothermal effects. This work highlights the great potential of the as-synthesized GA-Fe@BSA-PTX self-assembled nanoparticles as a multifunctional theranostic nanoplatform, offering compelling opportunities for theranostic applications in the clinic.

Graphene oxide / MnWO4 nanocomposite for magnetic resonance / photoacoustic dual-model imaging and tumor photothermo-chemotherapy

A multifunctional theranostic nanoplatform based on nanosized graphene oxide (GO) and MnWO4 has been developed by in situ growth of MnWO4 nanoparticles onto GO surfaces in a hyperthermia polyol medium containing polyethylene glycol (PEG). In comparison with GO and MnWO4/PEG, the near infrared (NIR) absorbance of the produced GO/MnWO4/PEG nanocomposite is significantly improved, resulting in an enhanced photothermal conversion capability and a good photoacoustic (PA) imaging performance. It is worth to note that the longitudinal relaxivity r1 of GO/MnWO4/PEG reaches impressively 11.34 mM−1 s−1 in a 0.5 T magnetic field, which is significantly higher than ordinary Mn(II)-based T1 agents. In vivo magnetic resonance and PA imaging demonstrate that GO/MnWO4/PEG could serve as an efficient bimodal contrast agent to guide the cancer treatment. GO/MnWO4/PEG shows a high loading capacity for anticancer drug doxorubicin hydrochloride (DOX) by noncovalent forces, and the drug release could be triggered by lower pH value and external NIR light. Effective synergistic photothermo-chemotherapy has been performed in xenograft 4T1 tumor models after intravenous administration of GO/MnWO4/PEG/DOX. No obvious toxicity and side effect have been observed during in vivo treatment. These positive results suggest the promising application of GO/MnWO4/PEG as a versatile nanoplatform for multimodal imaging-guided cancer synergistic therapy.

Development of Multifunctional Polydopamine Nanoparticles As a Theranostic Nanoplatform against Cancer Cells.

Although demanding, the development of multifunctional theranostic nanoplatforms is attracting considerable worldwide interest. Herein, a theranostic nanoplatform with multifunctions based on polydopamine (PDA) nanoparticles (NPs) was developed, owning dual-imaging and dual-therapy functions for cancer theranostic applications. PDA NPs were generated using a facile polymerization method under alkaline conditions, followed by poly(ethylene glycol) (PEG) modification. Then, the obtained NPs were loaded with IR820 and Fe3+ ions to produce the final PEGylated PDA/IR820/Fe3+ (PPIF) NPs. The PPIF NPs thus generated displayed increasingly brighter photoacoustic and magnetic resonance signals with increasing NP concentration and were demonstrated to be cytocompatible and effectively taken up and internalized into HeLa cells. Under near-infrared light irradiation, PPIF NPs can produce heat and reactive oxygen species for photothermal/photodynamic combined cancer therapy. In this study, the versatility of PDA NPs was demonstrated to be promising as a multifunctional nanoplatform for potential cancer theranostic applications.

Development of fluorinated polyplex nanoemulsions for improved small interfering RNA delivery and cancer therapy

We report the development of a small interfering RNA (siRNA) delivery vector based on cationic perfluorocarbon nanoemulsions. We have prepared perfluorodecalin (PFD) emulsions with a positive surface charge provided by a fluorinated poly(ethylenimine) (F-PEI). The fluorinated emulsion (F-PEI@PFD) reduced cytotoxicity of F-PEI and demonstrated effective binding with siRNAs to form nanosized emulsion polyplexes. The prepared emulsion polyplexes enhanced cellular uptake and improved endosomal escape of the siRNA. In addition to increased reporter gene silencing in multiple cancer cell lines, when compared with control F-PEI and PEI polyplexes, the siRNA emulsion polyplexes showed an excellent resistance to serum deactivation and maintained high activity, even in high-serum conditions. The F-PEI@PFD emulsion polyplexes carrying an siRNA to silence the expression of Bcl2 gene induced apoptosis and inhibited tumor growth in a melanoma mouse model in vivo and showed potential for in vivo ultrasound imaging. This study demonstrates the potential of F-PEI@PFD emulsions as a multifunctional theranostic nanoplatform for safe siRNA delivery, with integrated ultrasound imaging functionality.

Water-Dispersible Prussian Blue Hyaluronic Acid Nanocubes with Near-Infrared Photoinduced Singlet Oxygen Production and Photothermal Activities for Cancer Theranostics.

Design and development of photosensitizers that can efficiently convert energy of near-infrared (NIR) laser irradiation are of major importance for cancer photoassisted therapeutics. Herein, for the first time, it is demonstrated that Prussian blue (PB), a classic coordination compound, can act as a novel photosensitizer with efficient generation of singlet oxygen and excellent photothermal conversion via NIR photoirradiation-induced energy transfer. After modification with hyaluronic acid (HA), the as-prepared HA-modified PB nanocubes (HA@PB) are highly dispersible in aqueous and physiological solutions, as well as show excellent photothermal/photodynamic activities under NIR (808 nm) photoexcitation. On the basis of these features, HA@PB is used to study their in vitro and in vivo combined therapeutic effect. Owing to the CD44 ligand of HA, HA@PB have specific uptake by CD44-positive cells in vitro and can be precisely in vivo delivered to the tumor site. HA@PB as one of the synergistically photodynamic/photothermal combination nanoplatforms could achieve excellent therapeutic efficacy with targeted specificity under the guidance of dual-modality photoacoustic/infrared thermal imaging. Hence, this work is expected to pave the way for using PB-based nanomaterials as a promising multifunctional theranostic nanoplatform in biomedical fields.

Microenvironment-Driven Cascaded Responsive Hybrid Carbon Dots as a Multifunctional Theranostic Nanoplatform for Imaging-Traceable Gene Precise Delivery

Imaging-guided stimuli-responsive delivery systems based on nanomaterials for cancer theranostics have been recognized as promising alternatives to traditional therapies in clinic. How to integrate multiple response-mediated nanoproperty (i.e., charge, size, or stability) transitions into a cascaded manner to overcome multistage biological barriers which usually demand different and even opposing nanoproperties in each stage is still a challenge. Herein, a multistage and cascaded responsive theranostic nanoplatform for imaging-traceable TRAIL gene precise delivery was prepared by a cleavable PEGylated shell and a fluorescent carbon dot (CD)-based core. The CDs as the core were prefunctionalized with polyethylenimine end-capped disulfide-bond-bearing hyperbranched poly(amido amine) (HPAP), endowing the CDs with enhanced fluorescent quantum yield (27%), intracellular degradability, and efficient gene delivery capability. The shell was fabricated by dimethylmaleic acid modification of mPEG-PEI600 copolymer a...

In Vivo Targeted, Responsive, and Synergistic Cancer Nanotheranostics by Magnetic Resonance Imaging-Guided Synergistic High-Intensity Focused Ultrasound Ablation and Chemotherapy.

As one of the most representative noninvasive therapeutic modalities, high-intensity focused ultrasound (HIFU) has shown great promise for cancer therapy, but its low therapeutic efficacy and biosafety significantly hinder further extensive clinical translation and application. In this work, we report on the construction of a multifunctional theranostic nanoplatform to synergistically enhance the HIFU-therapeutic efficacy based on nanomedicine. A targeted and temperature-responsive theranostic nanoplatform (PFH/DOX@PLGA/Fe3O4-FA) has been designed and fabricated for efficient ultrasound/magnetic resonance dual-modality imaging-guided HIFU/chemo synergistic therapy. Especially, the folate was conjugated onto the surface of the nanoplatform for achieving active targeting to hepatoma cells by receptor-ligand interaction, which facilitates accumulation of the nanoplatforms into the tumor site. The integrated superparamagnetic iron oxide nanoparticles could generate the contrast enhancement in T2-weighted magnetic resonance imaging. By virtue of the thermal effect as generated by HIFU, liquid-gas phase transition of perfluorohexane (PFH) in nanocomposites was induced to generate PFH microbubbles, which achieved the contrast-enhanced ultrasound imaging and significantly improved the HIFU ablation efficacy. The loaded anticancer drugs could be released from the nanocomposites in a controllable manner (both pH and HIFU responsiveness). These multifunctional nanocomposites have been demonstrated to efficiently suppress the tumor growth based on the enhanced and synergistic chemotherapy and HIFU ablation, providing an efficient theranostic nanoplatform for cancer treatment.