Imaging-guided Synergistic Therapy Research Articles

Nanostructured cruciform phototheranostic agents for efficient multimodal imaging-guided type I photodynamic/photothermal synergistic therapy

One-component multimodel imaging-guided synergistic platform provides an attracting strategy for the precise cancer therapy. However, the construction of single molecules integrating near-infrared (NIR) II emission, multimodel-imaging and multiple therapeutic modalities still remains a great challenge. In this study, a series of organic phototheranostic agents (named PMY, MePMY and TPMY) based on a cross-shaped D-π-A framework were designed and synthesized, and their corresponding nanoparticles (NPs) were facilely fabricated by encapsulating them with an amphiphilic polymer. The twisted structure and lower band gaps of these compounds extended their emissions deep into the NIR-II region, and the narrow singlet-triplet energy gaps endowed them with highly efficient intersystem crossing from S1 to T1 state. Specifically, TPMY NPs exhibit NIR-II emission at 1022 nm, efficient generation of type I reactive oxygen species, and high photothermal conversion efficiency (37.8 %), as well as good photostability and biocompatibility. In vitro and in vivo experiments further revealed the excellent photoacoustic and photothermal imaging ability and superior tumoricidal activity of TPMY NPs, in which the tumor growth was effectively inhibited or even completely eradicated upon single administration and once light irradiation. This study thus provides a new insight into the design and development of intelligent phototheranostic agents for multimodel imaging-guided synergistic therapy which has potential in future practical applications.

A near-infrared phototheranostic probe for in vivo hyaluronidase detection and activatable imaging-guided synergistic therapy of triple negative breast cancer

A near-infrared phototheranostic probe for in vivo hyaluronidase detection and activatable imaging-guided synergistic therapy of triple negative breast cancer

Construction of Cu/ZIF-67/Prussian Blue Nanostructures with Photothermal-Enhanced Multizyme Activity for Cancer Therapy

Nanozymes that mimic the catalytic reaction of natural enzymes show great prospects for tumor catalytic therapy because they possess the properties of nanomaterials and natural enzymes. However, the therapeutic effect of nanozymes is restricted by the low catalytic efficiency and specific oxidation–reduction systems in the tumor microenvironment (TME), such as overexpressed glutathione (GSH) level. In order to improve the catalytic efficiency, a multifunctional nanozyme, Cu/zeolitic imidazolate framework-67 (ZIF-67)/Prussian blue (PB), was designed through the modification of Prussian blue (PB) on the surface of the copper-doped zeolitic imidazolate framework, which can be used for imaging-guided synergistic therapy with photothermal-enhanced multienzyme-like catalytic therapy and chemotherapy. The doping of Cu2+ provided better glutathione oxidase-like (GPx-like) activity and peroxidase-like (POD-like) activity to deplete GSH and increase the generation of •OH in TME. The modification of PB provided better catalase-like activity (CAT-like) to promote the production of O2 and enhance the multienzyme-like catalytic therapy. In vivo experiments showed a satisfactory anticancer effect. This work thus provided a strategy for designing a type of multifunctional nanozyme for imaging-guided combination therapy.

A Multilayered Mesoporous Gold Nanoarchitecture for Ultraeffective Near‐Infrared Light‐Controlled Chemo/Photothermal Therapy for Cancer Guided by SERS Imaging (Small 6/2023)

Chemo/Photothermal Therapy for Cancer Guided by SERS Imaging In article number 2206762, Mo Yang, Siu Hong Dexter Wong, and co-workers develop a multilayered mesoporous gold nanoarchitecture labeled with Raman reporters for ultraeffective surface-enhanced Raman scattering (SERS) imaging-guided synergistic therapy toward cancer. This nanoplatform enables efficient xenograft tumor model targeting with sensitive SERS imaging in vitro and in vivo for identifying the tumor cells and optimal therapeutic time point, thereby achieving the highest therapeutic outcome of noninvasive near-infrared triggered photothermal therapy and hyperthermia enhanced chemotherapy.

Cyclic enhancement of hypoxic microenvironment via an intelligent nanoamplifier for activated NIR-II fluorescence/photoacoustic imaging-guided precise synergistic therapy.

Tumor microenvironment (TME)-activated theranostics is a promising strategy to effectively identify small lesions, improve antitumor efficacy, and reduce the risk of undesired side effects. Hypoxia, as a common characteristic of TME, can serve as a preferred site for stimulus-dependent activation; however, tumor-hypoxia levels in various developmental stages exhibit different characteristics, severely limiting the response sensitivity. Herein, a circulating self-reinforcing hypoxic nanoamplifier (CGH NAs) is developed that utilizes a dual-chain reaction process (internal regulation, internal regulation) to achieve precise activation of NIR-II FL/photoacoustic (PA) imaging-guided synergistic therapy. Inspired by the positive correlation of nitroreductase (NTR) with hypoxia, the CGH NAs encapsulate CQ4T and GOx into NTR-sensitive hyaluronic acid-nitroimidazole (HA-NI) shell via a self-assembly approach, enabling aggregation-caused NIR-II FL quenching and tumor-accurate delivery. When CGH NAs efficiently accumulated in the tumor region, the intensive local NTR reduced hydrophobic -NO2 to hydrophilic -NH2, which lead to disassembly of CGH NAs. The released GOx could consume O2 (internal regulation) and glucose to cut off the energy supply, inducing tumor-starvation therapy; generate gluconic acid and H2O2 (oxidative stress). Meanwhile, the released CQ4T promoted rapid recovery of NIR-II FL signals for imaging-guided PDT, which could simultaneously deplete intratumoral O2 (external stimulation). Remarkably, the strengthened tumor-hypoxia levels in turn accelerated the NTR-responsive degradation of the CGH NAs, thereby achieving high-efficiency theranostic.

A multi-hit therapeutic nanoplatform for hepatocellular carcinoma: Dual stimuli-responsive drug release, dual-modal imaging, and in situ oxygen supply to enhance synergistic therapy.

Nanomedicine has been widely studied for the diagnosis and treatment of hepatocellular carcinoma (HCC). How to synthesize a nanoplatform possessing a high synergistic therapeutic efficacy remains a challenge in this emerging research field. In this study, a convenient all-in-one therapeutic nanoplatform (FTY720@AM/T7-TL) is designed for HCC. This advanced nanoplatform consists of multiple functional elements, including gold-manganese dioxide nanoparticles (AM), tetraphenylethylene (T), fingolimod (FTY720), hybrid-liposome (L), and T7 peptides (T7). The nanoplatform is negatively charged at physiological pH and can transit to a positively charged state once moving to acidic pH environments. The specially designed pH-responsive charge-reversal nanocarrier prolongs the half-life of nanodrugs in blood and improves cellular uptake efficiency. The platform achieves a sustained and controllable drug release through dual stimulus-response, with pH as the endogenous stimulus and near-infrared as the exogenous stimulus. Furthermore, the nanoplatform realizes in situ O2 generation by catalyzing tumor over-expressed H2O2, which alleviates tumor microenvironment hypoxia and improves photodynamic therapy. Both in vitro and in vivo studies show the prepared nanoplatform has good photothermal conversion, cellular uptake efficiency, fluorescence/magnetic resonance imaging capabilities, and synergistic anti-tumor effects. These results suggest that the prepared all-in-one nanoplatform has great potential for dual-modal imaging-guided synergistic therapy of HCC.

Cooperative coordination-mediated multi-component self-assembly of “all-in-one” nanospike theranostic nano-platform for MRI-guided synergistic therapy against breast cancer

Carrier-free multi-component self-assembled nano-systems have attracted widespread attention owing to their easy preparation, high drug-loading efficiency, and excellent therapeutic efficacy. Herein, MnAs-ICG nanospike was generated by self-assembly of indocyanine green (ICG), manganese ions (Mn2+), and arsenate (AsO43−) based on electrostatic and coordination interactions, effectively integrating the bimodal imaging ability of magnetic resonance imaging (MRI) and fluorescence (FL) imaging-guided synergistic therapy of photothermal/chemo/chemodynamic therapy within an “all-in-one” theranostic nano-platform. The as-prepared MnAs-ICG nanospike had a uniform size, well-defined nanospike morphology, and impressive loading capacities. The MnAs-ICG nanospike exhibited sensitive responsiveness to the acidic tumor microenvironment with morphological transformation and dimensional variability, enabling deep penetration into tumor tissue and on-demand release of functional therapeutic components. In vitro and in vivo results revealed that MnAs-ICG nanospike showed synergistic tumor-killing effect, prolonged blood circulation and increased tumor accumulation compared to their individual components, effectively resulting in synergistic therapy of photothermal/chemo/chemodynamic therapy with excellent anti-tumor effect. Taken together, this new strategy might hold great promise for rationally engineering multifunctional theranostic nano-platforms for breast cancer treatment.

Acid-Triggered H2O2 Self-Supplying Nanoplatform for 19F-MRI with Enhanced Chemo-Chemodynamic Therapy.

The real-time tracking and efficacy evaluation of therapeutic nanoplatforms especially in deep-tissues is of great importance but faces challenges. Meanwhile, chemodynamic therapy (CDT), relying on Fenton reaction by converting H2O2 into toxic hydroxyl radicals (•OH), has drawn wide interests in the fabrication of nanozymes for tumor therapy, while endogenous H2O2 is usually insufficient for effective CDT. Here, we report the pH-responsive multifunctional nanoplatforms consisting of copper peroxide (CP) nanoparticles, paclitaxel (PTX) and perfluoro-15-crown-5-ether (PFCE), for 19F magnetic resonance imaging guided and enhanced chemo-chemodynamic synergetic therapy with self-supplied H2O2 stemmed from the decomposition of CP nanoparticles under acid conditions in tumor. The decomposition of CP nanoparticles further promotes the release of PTX for enhanced chemotherapy. Both in vitro and in vivo results indicate that the efficient generation of •OH and drug release effectively inhibits tumor growth. Furthermore, 19F MRI signal can clearly track the fate of nanoplatforms in tumor and guide tumor treatment. This work provides a promising strategy for the rational design and construction of multifunctional nanoplatforms for imaging-guided synergistic therapy of deep seated tumor.

Facile one-step synthesis of NIR-Responsive siRNA-Inorganic hybrid nanoplatform for imaging-guided photothermal and gene synergistic therapy

Diagnosis-guided synergistic treatment based on innovative nanomaterials is of great significance for the development of anti-cancer therapies. However, the low delivery efficiency of therapeutic gene and the inability to trigger release on demand are still major obstacles impeding its wide application. Herein, we report an ultra-fast one-step method within 2 min to prepare a smart carrier, liposome-coated Prussian blue @ gold nano-flower, which is named LPAR after linking with tumor-targeting peptide. The versatile LPAR not only can respond to near-infrared (NIR) light, achieve the selective delivery and the controlled release of siRNA targeting the mutant gene of Kras at its codon-12 from Glycine (G) to Aspartic acid (D) (named as G12D mutant gene) in the malignant pancreatic tumors, but also efficiently convert the absorbed NIR light into the heat to realize gene-photothermal synergistic therapy both in vitro and in vivo. Theoretical simulation results reveal that the outstanding photothermal conversion efficiency of LPAR is mainly due to its higher electric field intensity and power density distributions. Furthermore, the LPAR possesses the capabilities for triple-modal imaging. Therefore, the developed NIR light-responsive LPAR has the potential to be served as a tumor-targeted nano-delivery system for imaging-guided synergistic therapy of cancers.

Near-Infrared multifunctional theranostic agent with Wave-Like aggregates modulated by substituent position effect

Precise design of organic photosensitizers (PSs) promoted the technological innovation for multimodal imaging-guided synergistic therapy. Nonetheless, various group substitution could not only optimize the basic photophysical behavior, but possibly change the aggregate, which handicaps the deep understanding of the “Formula-Aggergete-Property” relationship. Bearing this in mind, herein two isomers, named 6-TDE and 7-TDE, were prepared via substituting position modification. Among them, 6-TDE exhibited the grid-like structure, while 7-TDE presented wavy-like structure. Despite the aggregates were different, 6-TDE and 7-TDE shared common features including partly twisted backbone and non-overlapped-orbit, hence resulting in similar optical physical behavior such as decent extinction coefficient, near-IR emission, large stockes shifts, etc. Meanwhile, though two PSs could both generated Type-I and Type-II ROS, 7-TDE possessed smaller singlet–triplet splitting (ΔEST), which exhibited favorable ROS as well as outstanding mitochondrial targeting, achieving efficient photodynamic therapy (PDT) effect. During this process, mitochondrial autophagy could be tracked and observed effectively and in real-time. Moreover, 7-TDE presented outstanding performance in multimodal imaging, including fluorescence imaging (FLI), photoacousticimaging (PAI) and photothermal imaging (PTI). This study enriches the strategy of precise molecular engineering to optimize theranostic agents.

Liposome-Coated Arsenic-Manganese Complex for Magnetic Resonance Imaging-Guided Synergistic Therapy Against Carcinoma.

PurposeA liposome-coated arsenic–manganese complex, denoted as LP@MnAsx was constructed for the targeted delivery of arsenic trioxide (ATO) against carcinoma.MethodsArsenite, the prodrug of ATO, was encapsulated within a liposome via electrostatic interaction with the manganese ions. The as-prepared material was characterized with dynamic light scattering and transmission electron microscopy. The entrapment efficiency and drug loading of arsenic in the carrier were measured using inductively coupled plasma spectrometry. The in vitro release of arsenic was evaluated by using the dialysis bag method. Furthermore, the Fenton-like activity and in vitro cytodynamics research of LP@MnAsx were monitored in this work. And the cellular uptake study was used to investigate the in vitro entry mechanism. Furthermore, the cytotoxicity, cell apoptosis and cell cycle study were performed to evaluate the tumor-killing efficiency. Also, the pharmacokinetic and antitumor studies were investigated in HepG2 tumor-bearing nude mice.ResultsThe as-prepared LP@MnAsx possessed a spherical morphology, uniformly distributed hydrodynamic diameter, and excellent drug-loading efficiency. LP@MnAsx displayed robust stability and sustained-release profile under physiological environments. LP@MnAsx could degrade with high sensitivity to the pH variation in the tumor microenvironment. As such, this could lead to a burst release profile of Mn2+ and arsenite to achieve a synergistic therapy of chemodynamic therapy and chemotherapy. When compared to the carrier-free arsenate, in vitro experiments revealed that LP@MnAsx exhibited enhanced cellular uptake and tumor-killing efficiency. LP@MnAsx also demonstrated significantly enhanced tumor-specific in vivo distribution of arsenic, prolonged systemic circulation lifetime, and increased accumulation at the tumor site.ConclusionBased on the experimental results, LP@MnAsx is an ideal arsenic-based nanodelivery system, whereby it can improve the non-specific distribution of NaAsO2 in vivo. Thus, this work can expand the research and application of arsenic trioxide against solid tumors.

Dual-Stimuli-Responsive Nanotheranostics for Dual-Targeting Photothermal-Enhanced Chemotherapy of Tumor.

Stimuli-responsive nanotheranostics have been widely explored for precision medicine. Here, we developed a pH/light dual-stimuli-responsive nanotheranostic agent for biological/physical dual-targeting photothermal-enhanced chemotherapy of U87MG tumor. This nanotheranostic agent was composed of the RGD (Arg-Gly-Asp) peptide, melanin-coated magnetic nanoparticles (MMNs), doxorubicin (DOX), and indocyanine green (ICG), denoted as RMDI. The tumor accumulation of RMDI was simultaneously improved through biological active targeting by RGD and physical magnetic targeting by an external magnetic field at tumor tissues, which was proven by in vivo photoacoustic/magnetic resonance/fluorescence (PA/MR/FL) trimodal imaging. Under dual stimuli of the tumor acidic microenvironment and laser irradiation, both DOX and ICG were released in a controlled fashion, demonstrating impressive therapeutic outcomes against U87MG tumor both in vitro and in vivo, respectively. Owing to the synergistic photothermal/chemotherapy, the dual-stimuli-responsive and dual-targeting nanotheranostic agent completely ablated U87MG tumor in vivo without any tumor recurrence and biotoxicity. This nanotheranostic agent exhibited great potential in multimodal imaging-guided synergistic therapy of cancer.

Precise Molecular Engineering of Small Organic Phototheranostic Agents toward Multimodal Imaging-Guided Synergistic Therapy

Precise molecular engineering is the most fundamental and even a great challenging task for the development of small organic fluorophores used as phototheranostic agents in multimodal imaging-guided synergistic therapy. To the best of our knowledge, there have been no previous reports regarding the fine fabrication of molecular structure from a proof-of-concept study, providing a single molecule with all phototheranostic modalities. Herein, an electron donating-accepting (D-A) system is constructed by using triphenylamine derivatives as donors and diverse electron-deficient partners as acceptors, yielding aggregation-induced emission luminogens with tunable emission wavelength (up to 933 nm) and light absorption capability (ε up to 6.9 × 104 M-1 cm-1). Notably, by integrating the spin-orbit coupling-promoted carbonyl group and the strong stretching vibrations of -CN to the D-A systems, a highly performing phototheranostic agent, namely, MeTIC, is constructed. When encapsulating MeTIC into nanovehicles, the obtained MeTIC nanoparticles show excellent performance in multimodality theranostics for cancer treatment. This work is expected to provide an organic phototheranostic agent designing principle for potential clinical trials.

Recent Advances in Combination of Copper Chalcogenide-Based Photothermal and Reactive Oxygen Species-Related Therapies.

In recent times, the copper chalcogenide (Cu2-xE, E = S, Se, Te, 0 ≤ x ≤ 1)-based nanomaterials have emerged as potent photothermal agents for photothermal therapy (PTT) because of their advantageous features, such as the low cost, reduced toxicity, biodegradability, and strong absorption of near-infrared (NIR) light in a relatively wide range of wavelength. Nevertheless, the applicability of Cu2-xE-based PTT is limited because of its inadequate photothermal conversion efficiency, as well as insufficient destruction of the tumor area unexposed to the NIR laser. Fortunately, Cu2-xE nanomaterials also act as photosensitizers or Fenton-reaction catalysts to produce reactive oxygen species (ROS), referring to ROS-related therapy (RRT), which could further eradicate cancer cells to address the aforementioned limitations of PTT. Moreover, PTT improves RRT based on photodynamic therapy (PDT), sonodynamic therapy (SDT), chemodynamic therapy (CDT), and radiotherapy (RT) in different ways. Inspired by these facts, integrating Cu2-xE-based PTT with RRT into a single nanoplatform seems an ideal strategy to achieve synergistically therapeutic effects for cancer treatment. Herein, we discuss the synergetic mechanisms, composition, and performances of recent nanoplatforms for the combination of Cu2-xE-based PTT and RRT. In addition, we give a brief overview on some specific strategies for the further improvement of Cu2-xE-based PTT and RRT combined cancer treatment to enable the complete eradication of cancer cells, such as realizing the imaging-guided synergistic therapy, promoting deep tumor penetration of the nanosystems, and boosting O2 or H2O2 in the tumor microenvironment. Finally, we summarize with intriguing perspectives, focusing on the future tendencies for their clinical application.

Flexible Photothermal Assemblies with Tunable Gold Patterns for Improved Imaging-Guided Synergistic Therapy.

Self-assembly of gold nanoparticles demonstrates a promising approach to realize enhanced photoacoustic imaging (PAI) and photothermal therapy (PTT) for accurate diagnosis and efficient cancer therapy. Herein, unique photothermal assemblies with tunable patterns of gold nanoparticles (including arcs, rings, ribbons, and vesicles) on poly(lactic-co-glycolic acid) (PLGA) spheres are constructed taking advantage of emulsion-confined and polymer-directed self-assembly strategies. The influencing factors and formation mechanism to produce the assemblies are investigated in details. Both the emulsion structure and migration behaviors of amphiphilic block copolymer tethered gold nanoparticles are found to contribute to the formation of versatile photothermal assemblies. Hyaluronic acid-modified R-PLGA-Au (RPA) exhibits outstanding photothermal performances under NIR laser irradiation, which is induced by strong plasmonic coupling between adjacent gold nanoparticles. It is interesting that secondary assembly of RPA can be triggered by NIR laser irradiation. Prolonged residence time in tumors is achieved after RPA assemblies are fused into superstructures with larger sizes, realizing real-time monitoring of the therapeutic processes via PAI with enhanced photoacoustic signals. Notably, synergistic effect resulting from PTT-enhanced chemotherapy is realized to demonstrate high antitumor performance. This work provides a facile strategy to construct flexible photothermal assemblies with favorable properties for imaging-guided synergistic therapy.

Coordination Nanosheets of Phthalocyanine as Multifunctional Platform for Imaging-Guided Synergistic Therapy of Cancer.

"All-in-one" nanodrugs integrating various functionalities into one nanosystem are highly desired for cancer treatment. Coordination nanosheets as one type of two dimensional (2D) nanomaterials offer great opportunities, but there is lack of enough candidates. Here, a new kind of coordination nanosheets based on phthalocyanine are constructed. Manganese phthalocyanine (MnPc) tetracarboxylic acid is employed as photoactive ligand to form MnPc nanosheets; meanwhile, hyaluronic acid (HA) is coated on their surface. The obtained MnPc@HA nanosheets exhibit superior near-infrared (NIR) photothermal effect with photothermal conversion efficiency of 72.3%, much higher than those of the previously reported photothermal agents. Due to their 2D nanostructures, MnPc@HA nanosheets possess superhigh drug-loading capacity for chemotherapy drug curcumin. With HA as a targeting group, the nanosheets selectively accumulated in CD44 overexpressed tumors, followed by drug release under the control of NIR light. Moreover, MnPc@HA nanosheets with intrinsic paramagnetism can serve as T1 contrast agent for magnetic resonance imaging. The synergistic effect of phototherapy and chemotherapy endows curcumin-loaded MnPc@HA nanosheets with superior tumor-eradicating efficacy. Besides, MnPc@HA nanosheets are biocompatible and safe for biomedical applications. This work provides novel insight for developing new multifunctional platforms based on 2D coordination nanosheets to synergistically combat cancer.

AIEgen functionalized inorganic–organic hybrid nanomaterials for cancer diagnosis and therapy

AIEgen functionalized inorganic–organic hybrid nanomaterials with multifunctions can be used for cancer diagnosis and imaging-guided synergistic therapy.

A highly active (102) surface-induced rapid degradation of a CuS nanotheranostic platform for in situ T1-weighted magnetic resonance imaging-guided synergistic therapy.

Polyvinylpyrrolidone-modified CuS nanocrystals (CuS NCs) with high photothermal conversion efficiency (46%) and pH and near-infrared (NIR) light-triggered degradation properties are a promising nanotheranostic platform for in situ magnetic resonance imaging (MRI)-guided synergistic photothermal and photodynamic therapy. On the one hand, the (102) surface of CuS NCs has a small bandgap based on density functional theory, which leads to high photothermal conversion efficiency. On the other hand, the S vacancy formation energy of the (102) surface is favourable. On entry into tumor cells through endocytosis, the S2- ions on the (102) surface of CuS NCs can be easily oxidized under the tumor microenvironment and 808 nm laser irradiation; then, a large amount of Cu+ ions can be released from CuS NCs and accelerate the degradation of nanocrystals. Cu+ ions can generate reactive oxygen species (ROS) under the tumor microenvironment and 808 nm laser irradiation. Meanwhile, the oxidation product Cu2+ ions can be generated from the oxidized Cu+ ions and applied for in situ T1-weighted magnetic resonance imaging. Moreover, the biodegradable CuS NCs possess a high tumor uptake and can be rapidly excreted with a low long-term retention/toxicity. Therefore, degradable and multifunctional CuS NCs are a safe and efficient candidate for the diagnosis and treatment of cancer.

Triple-Modal Imaging-Guided Chemo-Photothermal Synergistic Therapy for Breast Cancer with Magnetically Targeted Phase-Shifted Nanoparticles.

Current nanodrug-based cancer therapy is susceptible to the problems of rapid clearance from circulation and limited therapeutic efficacy. Herein, we report a magnetically targeted and photothermal-triggered drug release nanotheranostics system based on superparamagnetic iron oxide (Fe3O4), IR780, doxorubicin (DOX), and perfluoropentane (PFP) entrapped poly-lactide- co-glycolide (PLGA) nanoparticles (IR780/Fe3O4@PLGA/PFP/DOX NPs) for triple-modal imaging-guided synergistic therapy of breast cancer. In this work, IR780 and Fe3O4 convert light into heat, which triggers DOX release from IR780/Fe3O4@PLGA/PFP/DOX NPs and a phase-shift thermoelastic expansion of PFP; this procedure further accelerates the DOX release and tissue extrusion deformation. Fe3O4 NPs also serve as the target moiety by an external magnet directed to the tumor. Specifically, the IR780/Fe3O4@PLGA/PFP/DOX NPs can be used for triple-modal imaging, including near infrared fluorescence, magnetic resonance, and ultrasound. Furthermore, the antitumor therapy studies reveal the extraordinary performance of IR780/Fe3O4@PLGA/PFP/DOX NPs in magnetically targeted synergistic chemo-photothermal therapy of cancer. Therefore, the multifunctional IR780/Fe3O4@PLGA/PFP/DOX NPs guided by the magnetic field show a great potential for cancer theranostics.

BSA-Bioinspired Gadolinium Hybrid-Functionalized Hollow Gold Nanoshells for NIRF/PA/CT/MR Quadmodal Diagnostic Imaging-Guided Photothermal/Photodynamic Cancer Therapy.

Multimodal imaging-guided synergistic therapy promises a more accurate diagnosis and higher therapeutic efficiency than single imaging modality or their simple "mechanical" combination. In this research, we have constructed an innovative multifunctional drug delivery platform by gadolinium (Gd)-based bovine serum albumin (BSA) hybrid-coated hollow gold nanoshells (Au@BSA-Gd). The obtained nanoparticles exhibited excellent photothermal effect and computed tomography (CT)/photoacoustic (PA) activity. Besides, the BSA-bioinspired gadolinium complex endowed the nanoparticles with an excellent T1 contrast agent for magnetic resonance imaging (MRI). In addition, the near-infrared (NIR) absorbing phototherapeutic agent [indocyanine green (ICG)] was loaded into the Au@BSA-Gd nanoparticles because of their unique, hollow, and porous structures, thus possessing photodynamic/photothermal property and near-infrared fluorescence (NIRF)/PA imaging capability. As a result, a combined cancer therapy containing the photothermal therapy of Au@BSA-Gd and the synchronous photodynamic/photothermal therapy of ICG was constructed. Furthermore, the well-designed nanocomposites with multiple integrated modalities enabled them to be an ideal nanotheranostic agent for NIRF/PA/CT/MR quadmodal imaging. Therefore, the ICG-loaded albumin-bioinspired gadolinium hybrid-functionalized hollow gold nanoshells (ICG-Au@BSA-Gd) hold great promise as a theranostic platform for simultaneous therapeutic monitoring and precise cancer therapy.