Plant Polyphenol‐Assisted Green Synthesis of Hollow CoPt Alloy Nanoparticles for Dual‐Modality Imaging Guided Photothermal Therapy

Theranostic nanomedicines that integrate diagnostic and therapeutic moieties into a single nanoscale platform are playing an increasingly important role in fighting cancer. Here, a facile and green synthetic strategy for hollow CoPt alloy nanoparticles (HCPA‐NPs) using plant polyphenols as assisted agents is reported for the first time. This novel strategy enables size‐controlled synthesis of HCPA‐NPs through the control of the molecular sizes of polyphenols. It is also a versatile strategy for synthesizing other hollow alloy nanoparticles with various metal compositions due to the diverse metal‐chelating ability of the polyphenols. Further studies show that HCPA‐NPs have good biocompatibility and can be successfully implemented for magnetic resonance and photoacoustic dual‐modal imaging guided photothermal therapy. This work brings new insights for the green synthesis of hollow nanoparticles and extends these biocompatible nanoparticles for theranostic applications.     

Facile and Scalable Synthesis of Novel Spherical Au Nanocluster Assemblies@Polyacrylic Acid/Calcium Phosphate Nanoparticles for Dual‐Modal Imaging‐Guided Cancer Chemotherapy

Engineering novel theranostic agents with both imaging and therapeutic functions have profound impact on molecular diagnostics, imaging, and therapeutics. In this paper, we develop for the first time a simple, scalable, and reproducible route to synthesize novel multifunctional spherical Au nanoclusters assemblies encapsulated by a polyacylic acid (PAA)/calcium phosphate (CaP) shell with aggregation enhanced fluorescence property (designated as AuNCs‐A@PAA/CaP). Furthermore, the resulting AuNCs‐A@PAA/CaP nanoparticles (NPs) possess a high payload of doxorubicin as synergetic pH‐sensitive drug delivery vehicles to employ for dual‐modal computed tomography (CT) and fluorescence imaging‐guided liver cancer chemotherapy in vivo. The results reveal that AuNCs‐A@PAA/CaP NPs not only provide excellent bimodal CT and fluorescence contrast imaging but also present efficient tumor ablation under the guidance of CT and fluorescence imaging, to achieve excellent chemotherapeutic efficacy to the hepatocarcinoma cell line (H‐22) bearing mice through intravenous injection. Comprehensive blood tests and careful histological examinations reveal no apparent toxicity of AuNCs‐A@PAA/CaP NPs. Our work highlights the great promise of AuNCs‐A@PAA/CaP NPs for guiding and monitoring the chemotherapeutic process using simultaneous dual‐modality CT and fluorescence imaging through a single theranostic agent.     

Core–Satellite Polydopamine–Gadolinium‐Metallofullerene Nanotheranostics for Multimodal Imaging Guided Combination Cancer Therapy

Integration of magnetic resonance imaging (MRI) and other imaging modalities is promising to furnish complementary information for accurate cancer diagnosis and imaging‐guided therapy. However, most gadolinium (Gd)–chelator MR contrast agents are limited by their relatively low relaxivity and high risk of released‐Gd‐ions‐associated toxicity. Herein, a radionuclide‐⁶⁴Cu‐labeled doxorubicin‐loaded polydopamine (PDA)–gadolinium‐metallofullerene core–satellite nanotheranostic agent (denoted as CDPGM) is developed for MR/photoacoustic (PA)/positron emission tomography (PET) multimodal imaging‐guided combination cancer therapy. In this system, the near‐infrared (NIR)‐absorbing PDA acts as a platform for the assembly of different moieties; Gd₃N@C₈₀, a kind of gadolinium metallofullerene with three Gd ions in one carbon cage, acts as a satellite anchoring on the surface of PDA. The as‐prepared CDPGM NPs show good biocompatibility, strong NIR absorption, high relaxivity (r ₁ = 14.06 mM^?1 s^?1), low risk of release of Gd ions, and NIR‐triggered drug release. In vivo MR/PA/PET multimodal imaging confirms effective tumor accumulation of the CDPGM NPs. Moreover, upon NIR laser irradiation, the tumor is completely eliminated with combined chemo‐photothermal therapy. These results suggest that the CDPGM NPs hold great promise for cancer theranostics.     

J‐Aggregates of Organic Dye Molecules Complexed with Iron Oxide Nanoparticles for Imaging‐Guided Photothermal Therapy Under 915‐nm Light

Recently, the development of nano‐theranostic agents aiming at imaging guided therapy has received great attention. In this work, a near‐infrared (NIR) heptamethine indocyanine dye, IR825, in the presence of cationic polymer, polyallylamine hydrochloride (PAH), forms J‐aggregates with red‐shifted and significantly enhanced absorbance. After further complexing with ultra‐small iron oxide nanoparticles (IONPs) and the followed functionalization with polyethylene glycol (PEG), the obtained IR825@PAH‐IONP‐PEG composite nanoparticles are highly stable in different physiological media. With a sharp absorbance peak, IR825@PAH‐IONP‐PEG can serve as an effective photothermal agent under laser irradiation at 915 nm, which appears to be optimal in photothermal therapy application considering its improved tissue penetration compared with 808‐nm light and much lower water heating in comparison to 980‐nm light. As revealed by magnetic resonance (MR) imaging, those nanoparticles after intravenous injection exhibit high tumor accumulation, which is then harnessed for in vivo photothermal ablation of tumors, achieving excellent therapeutic efficacy in a mouse tumor model. This study demonstrates for the first time that J‐aggregates of organic dye molecules are an interesting class of photothermal material, which when combined with other imageable nanoprobes could serve as a theranostic agent for imaging‐guided photothermal therapy of cancer.     

The Nanoassembly of an Intrinsically Cytotoxic Near‐Infrared Dye for Multifunctionally Synergistic Theranostics

The combination of diagnostic and therapeutic functions in a single theranostic nanoagent generally requires the integration of multi‐ingredients. Herein, a cytotoxic near‐infrared (NIR) dye (IR‐797) and its nanoassembly are reported for multifunctional cancer theranostics. The hydrophobic IR‐797 molecules are self‐assembled into nanoparticles, which are further modified with an amphiphilic polymer (C18PMH‐PEG5000) on the surface. The prepared PEG‐IR‐797 nanoparticles (PEG‐IR‐797 NPs) possess inherent cytotoxicity from the IR‐797 dye and work as a chemotherapeutic drug which induces apoptosis of cancer cells. The IR‐797 NPs are found to have an ultrahigh mass extinction coefficient (444.3 L g^?1 cm^?1 at 797 nm and 385.9 L g^?1 cm^?1 at 808 nm) beyond all reported organic nanomaterials (<40 L g^?1 cm^?1) for superior photothermal therapy (PTT). In addition, IR‐797 shows some aggregation‐induced‐emission (AIE) properties. Combining the merits of good NIR absorption, high photothermal energy conversion efficiency, and AIE, makes the PEG‐IR‐797 NPs useful for multimodal NIR AIE fluorescence, photoacoustic, and thermal imaging‐guided therapy. The research exhibits the possibility of using a single ingredient and entity to perform multimodal NIR fluorescence, photoacoustic, and thermal imaging‐guided chemo‐/photothermal combination therapy, which may trigger wide interest from the fields of nanomedicine and medicinal chemistry to explore multifunctional theranostic organic molecules.     

A Self‐Assembled Biocompatible Nanoplatform for Multimodal MR/Fluorescence Imaging Assisted Photothermal Therapy and Prognosis Analysis

The need for better imaging assisted cancer therapy calls for new biocompatible agents with excellent imaging and therapeutic capabilities. This study successfully fabricates albumin‐cooperated human serum albumin (HSA)‐GGD‐ICG nanoparticles (NPs), which are comprised of a magnetic resonance (MR) contrast agent, glycyrrhetinic‐acid‐modified gadolinium (III)‐1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetate (GGD), and a fluorescence (FL) dye, indocyanine green (ICG), for multimodal MR/FL imaging assisted cancer therapy. These HSA‐GGD‐ICG NPs with excellent biocompatibility are stable under physiological conditions, and exhibit enhanced T₁ contrast capability and improved fluorescence imaging capacity. In vitro experiments reveal an apparent effect of the NPs in killing tumor cells under low laser irradiation, due to the enhanced photothermal conversion efficiency (≈85.1%). Importantly, multimodal MR/FL imaging clearly shows the in vivo behaviors and the efficiency of tumor accumulation of HSA‐GGD‐ICG NPs, as confirmed by a pharmacokinetic study. With the guidance of multimodal imaging, photothermal therapy is subsequently conducted, which demonstrates again high photothermal conversion capability for eliminating tumors without relapse. Notably, real‐time monitoring of tumor ablation for prognosis and therapy evaluation is also achieved by MR imaging. This strategy of constructing nanoplatforms through albumin‐mediated methods is both convenient and efficient, which would enlighten the design of multimodal imaging assisted cancer therapy for potential clinical translation.     

Encapsulated Conjugated Oligomer Nanoparticles for Real‐Time Photoacoustic Sentinel Lymph Node Imaging and Targeted Photothermal Therapy

Noninvasive and nonionizing imaging of sentinel lymph nodes (SLN) is highly desirable for the detection of breast cancer metastasis through sentinel lymph node biopsy. Photoacoustic (PA) imaging is an emerging imaging technique that can serve as a suitable approach for SLN imaging. Herein, novel conjugated oligomer based nanoparticles (NPs) with strong NIR absorption, good biocompatibility, excellent PA contrast, and good photothermal conversion efficiency are reported. Real‐time PA imaging of SLN reveals high resolution of the NPs via injection from the left forepaw pad. In addition, the surface functionalized NPs can target breast cancer cells and kill them efficiently and specifically through photothermal therapy upon 808 nm laser irradiation. This work shows great potential of the nanoparticle PA contrast agent to serve as a multifunctional probe for photothermal therapy at SLNs to achieve the inhibition of cancer cell metastasis in the near future.     

NIR‐Responsive Polycationic Gatekeeper‐Cloaked Hetero‐Nanoparticles for Multimodal Imaging‐Guided Triple‐Combination Therapy of Cancer

Responsive multifunctional organic/inorganic nanohybrids are promising for effective and precise imaging‐guided therapy of cancer. In this work, a near‐infrared (NIR)‐triggered multifunctional nanoplatform comprising Au nanorods (Au NRs), mesoporous silica, quantum dots (QDs), and two‐armed ethanolamine‐modified poly(glycidyl methacrylate) with cyclodextrin cores (denoted as CD‐PGEA) has been successfully fabricated for multimodal imaging‐guided triple‐combination treatment of cancer. A hierarchical hetero‐structure is first constructed via integration of Au NRs with QDs through a mesoporous silica intermediate layer. The X‐ray opacity and photoacoustic (PA) property of Au NRs are utilized for tomography (CT) and PA imaging, and the imaging sensitivity is further enhanced by the fluorescent QDs. The mesoporous feature of silica allows the loading of a typical antitumor drug, doxorubicin (DOX), which are sealed by the polycationic gatekeepers, low toxic hydroxyl‐rich CD‐PGEA/pDNA complexes, realizing the co‐delivery of drug and gene. The photothermal effect of Au NRs is utilized for photothermal therapy (PTT). More interestingly, such photothermal effect also induces a cascade of NIR‐triggered release of DOX through the facilitated detachment of CD‐PGEA gatekeepers for controlled chemotherapy. The resultant chemotherapy and gene therapy for glioma tumors are complementary for the efficiency of PTT. This work presents a novel responsive multifunctional imaging‐guided therapy platform, which combines fluorescent/PA/CT imaging and gene/chemo/photothermal therapy into one nanostructure.     

Dual‐Stimuli Responsive Nanotheranostics for Multimodal Imaging Guided Trimodal Synergistic Therapy

Multimodal imaging guided synergistic therapy promises more accurate diagnosis than any single imaging modality, and higher therapeutic efficiency than any single one or their simple “mechanical” combination. Herein, we report a dual‐stimuli responsive nanotheranostic based on a hierarchical nanoplatform, composed of mesoporous silica‐coated gold nanorods (GNR@SiO2), Indocyanine Green (ICG), and 5‐fluorouracil (5‐FU), for in vivo multimodal imaging guided synergistic therapy. The 5‐FU loaded ICG‐conjugated silica‐coated gold nanorods (GNR@SiO2‐5‐FU‐ICG) was able to response specifically to the two stimuli of pH change and near‐infrared (NIR) light irradiation. Both the NIR light irradiation and acidic environment accelerated the 5‐FU release. Meanwhile, the heat generation and singlet oxygen production can be induced by GNR@SiO2‐5‐FU‐ICG upon light irradiation. Most intriguingly, the nanoplatform also promises multimodal imaging such as two‐photon luminescence, fluorescence, photoacoustic, photothermal imaging, as well as trimodal synergistic therapy such as photothermal therapy (PTT), photodynamic therapy (PDT), and chemotherapy. The cancer theranostic capability of GNR@SiO2‐5‐FU‐ICG was evaluated both in vitro and in vivo. The trimodal synergistic therapy with the guidance of multimodal imaging exhibited remarkably enhanced treatment efficacy. This concept of a hierarchical nanoplatform integrates multiple diagnostic/therapeutic modalities into one platform, which can potentially be applied as personalized nanomedicine with drug delivery, diagnosis, and treatment.     

Multifunctional RbxWO3 Nanorods for Simultaneous Combined Chemo‐photothermal Therapy and Photoacoustic/CT Imaging

Light‐triggered drug delivery based on near‐infrared (NIR)‐mediated photothermal nanocarriers has received tremendous attention for the construction of cooperative therapeutic systems in nanomedicine. Herein, a new paradigm of light‐responsive drug carrier that doubles as a photothermal agent is reported based on the NIR light‐absorber, Rb _x WO₃ (rubidium tungsten bronze, Rb‐TB) nanorods. With doxorubicin (DOX) payload, the DOX‐loaded Rb‐TB composite (Rb‐TB‐DOX) simultaneously provides a burst‐like drug release and intense heating effect upon 808‐nm NIR light exposure. MTT assays show the photothermally enhanced antitumor activity of Rb‐TB‐DOX to the MCF‐7 cancer cells. Most remarkably, Rb‐TB‐DOX combined with NIR irradiation also shows dramatically enhanced chemotherapeutic effect to DOX‐resistant MCF‐7 cells compared with free DOX, demonstrating the enhanced efficacy of combinational chemo‐photothermal therapy for potentially overcoming drug resistance in cancer chemotherapy. Furthermore, in vivo study of combined chemo‐photothermal therapy is also conducted and realized on pancreatic (Pance‐1) tumor‐bearing nude mice. Apart from its promise for cancer therapy, the as‐prepared Rb‐TB can also be employed as a new dual‐modal contrast agent for photoacoustic tomography and (PAT) X‐ray computed tomography (CT) imaging because of its high NIR optical absorption capability and strong X‐ray attenuation ability, respectively. The results presented in the current study suggest promise of the multifunctional Rb _x WO₃ nanorods for applications in cancer theranostics.     

An NIR‐Fluorophore‐Based Therapeutic Endoplasmic Reticulum Stress Inducer

The endoplasmic reticulum (ER) stress signaling or unfolded protein response (UPR) is a common feature of many human diseases, including cancer. Excessive activation of ER stress directly induces cell death, holding a new promising strategy for the therapeutic intervention of cancer. Current ER‐stress‐inducing agents mainly target UPR components or proteasomes, which exert limited treatment efficacy and undesired side effects due to unselective ER stress and poor tumor‐specific distribution. In this study, a unique near‐infrared (NIR) fluorophore, IR‐34, is synthesized and identified to selectively and efficiently trigger tumoricidal ER stress by targeting the mitochondrial protein NDUFS1. IR‐34 is demonstrated to specifically accumulate in living cancer cells for tumor NIR imaging and drastically inhibit tumor growth and recurrence without causing apparent toxicity. Thus, this multifunctional NIR fluorophore may represent a novel theranostic agent for tumor imaging‐guided treatment and also strengthens the idea that mitochondria could be a useful target for therapeutic ER stress in cancer cells.     

A New Co‐P Nanocomposite with Ultrahigh Relaxivity for In Vivo Magnetic Resonance Imaging‐Guided Tumor Eradication by Chemo/Photothermal Synergistic Therapy

Design of new nanoagents that intrinsically have both diagnostic imaging and therapeutic capabilities is highly desirable for personalized medicine. In this work, a novel nanotheranostic agent is fabricated based on polydopamine (PDA)‐functionalized Co‐P nanocomposites (Co‐P@PDA) for magnetic resonance imaging (MRI)‐guided combined photothermal therapy and chemotherapy. The ultrahigh relaxivity of 224.61 mm ^?1 s^?1 can enable Co‐P@PDA to be applied as an excellent contrast agent for MRI in vitro and in vivo, providing essential and comprehensive information for tumor clinical diagnosis. Moreover, Co‐P@PDA exhibit excellent photothermal performance owing to the strong near‐infrared (NIR) absorbance of both Co‐P nanocomposite and PDA. Highly effective ablation of tumors is achieved in a murine tumor model because the NIR laser not only induces photothermal effects but also triggers the chemotherapeutic drug on‐demand release, which endows the Co‐P@PDA with high curative effects but little toxicity and few side effects. These findings demonstrate that Co‐P@PDA are promising agents for highly effective and precise antitumor treatment and warrant exploration as novel theranostic nanoagents with good potential for future clinical translation.     

Polyphenol‐Inspired Facile Construction of Smart Assemblies for ATP‐ and pH‐Responsive Tumor MR/Optical Imaging and Photothermal Therapy

Smart assemblies have attracted increased interest in various areas, especially in developing novel stimuli‐responsive theranostics. Herein, commercially available, natural tannic acid (TA) and iron oxide nanoparticles (Fe₃O₄ NPs) are utilized as models to construct smart magnetic assemblies based on polyphenol‐inspired NPs–phenolic self‐assembly between NPs and TA. Interestingly, the magnetic assemblies can be specially disassembled by adenosine triphosphate, which shows a stronger affinity to Fe₃O₄ NPs than that of TA and partly replaces the surface coordinated TA. The disassembly can further be facilitated by the acidic environment hence causing the remarkable change of the transverse relaxivity and potent “turn‐on” of fluorescence (FL) signals. Therefore, the assemblies for specific and sensitive tumor magnetic resonance and FL dual‐modal imaging and photothermal therapy after intravenous injection of the assemblies are successfully employed. This work not only provides understandings on the self‐assembly between NPs and polyphenols, but also will open new insights for facilely constructing versatile assemblies and extending their biomedical applications.     

Photosensitizer‐Conjugated Albumin−Polypyrrole Nanoparticles for Imaging‐Guided In Vivo Photodynamic/Photothermal Therapy

Conjugated polymers with strong absorbance in the near‐infrared (NIR) region have been widely explored as photothermal therapy agents due to their excellent photostability and high photothermal conversion efficiency. Herein, polypyrrole (PPy) nanoparticles are fabricated by using bovine serum albumin (BSA) as the stabilizing agent, which if preconjugated with photosensitizer chlorin e6 (Ce6) could offer additional functionalities in both imaging and therapy. The obtained PPy@BSA‐Ce6 nanoparticles exhibit little dark toxicity to cells, and are able to trigger both photodynamic therapy (PDT) and photothermal therapy (PTT). As a fluorescent molecule that in the meantime could form chelate complex with Gd³⁺, Ce6 in PPy@BSA‐Ce6 nanoparticles after being labeled with Gd³⁺ enables dual‐modal fluorescence and magnetic resonance (MR) imaging, which illustrate strong tumor uptake of those nanoparticles after intravenous injection into tumor‐bearing mice. In vivo combined PDT and PTT treatment is then carried out after systemic administration of PPy@BSA‐Ce6, achieving a remarkably improved synergistic therapeutic effect compared to PDT or PTT alone. Hence, a rather simple one‐step approach to fabricate multifunctional nanoparticles based on conjugated polymers, which appear to be promising in cancer imaging and combination therapy, is presented.     

Ultrastable Near‐Infrared Conjugated‐Polymer Nanoparticles for Dually Photoactive Tumor Inhibition

It is highly desired that satisfactory photoactive agents with ideal photophysical characteristics are explored for potent cancer phototherapeutics. Herein, bifunctional nanoparticles of low‐bandgap donor–acceptor (D–A)‐type conjugated‐polymer nanoparticles (CP‐NPs) are developed to afford a highly efficient singlet‐to‐triplet transition and photothermal conversion for near‐infrared (NIR) light‐induced photodynamic (PDT)/photothermal (PTT) treatment. CP‐NPs display remarkable NIR absorption with the peak at 782 nm, and perfect resistance to photobleaching. Photoexcited CP‐NPs undergo singlet‐to‐triplet intersystem crossing through charge transfer in the excited D–A system and simultaneous nonradiative decay from the electron‐deficient electron acceptor isoindigo derivative under single‐wavelength NIR light irradiation, leading to distinct singlet oxygen quantum yield and high photothermal conversion efficiency. Moreover, the CP‐NPs display effective cellular uptake and cytoplasmic translocation from lysosomes, as well as effective tumor accumulation, thus promoting severe light‐triggered damage caused by favorable reactive oxygen species (ROS) generation and potent hyperthermia. Thus, CP‐NPs achieve photoactive cell damage through their photoconversion ability for synergistic PDT/PTT treatment with tumor ablation. The proof‐of‐concept design of D–A‐type conjugated‐polymer nanoparticles with ideal photophysical characteristics provides a general approach to afford potent photoactive cancer therapy.     

A Smart Responsive Dual Aptamers‐Targeted Bubble‐Generating Nanosystem for Cancer Triplex Therapy and Ultrasound Imaging

The absence of targeted, single treatment methods produces low therapeutic value for treating cancers. To increase the accumulation of drugs in tumors and improve the treatment effectiveness, near‐infrared 808 nm photothermal responsive dual aptamers‐targeted docetaxel (DTX)‐containing nanoparticles is proposed. In this system, DTX and NH₄HCO₃ are loaded in thermosensitive liposomes. The surface of liposomes is coated with gold nanoshells and connected with sulfydryl (SH? ) modified AS1411 and S2.2 aptamers. The nanosystem has good biocompatibility and uniform size (diameter about 200 nm). The drug is rapidly released, reaching a maximum amount (84%) at 4 h under 808 nm laser irradiation. The experiments conducted in vitro and in vivo demonstrate the nanosystem can synergistically inhibit tumor growth by combination of chemotherapy, photothermal therapy, and biological therapy. Dual ligand functionalization significantly increases cellular uptake on breast cancer cell line (MCF‐7) cells and achieves ultrasound imaging (USI) at tumor site. The results indicate that this drug delivery system is a promising theranostic agent involving light‐thermal response at tumor sites, dual ligand targeted triplex therapy, and USI.     

Mitochondria‐Targeting Magnetic Composite Nanoparticles for Enhanced Phototherapy of Cancer

Photothermal therapy (PTT) and photodynamic therapy (PDT) are promising cancer treatment modalities in current days while the high laser power density demand and low tumor accumulation are key obstacles that have greatly restricted their development. Here, magnetic composite nanoparticles for dual‐modal PTT and PDT which have realized enhanced cancer therapeutic effect by mitochondria‐targeting are reported. Integrating PTT agent and photosensitizer together, the composite nanoparticles are able to generate heat and reactive oxygen species (ROS) simultaneously upon near infrared (NIR) laser irradiation. After surface modification of targeting ligands, the composite nanoparticles can be selectively delivered to the mitochondria, which amplify the cancer cell apoptosis induced by hyperthermia and the cytotoxic ROS. In this way, better photo therapeutic effects and much higher cytotoxicity are achieved by utilizing the composite nanoparticles than that treated with the same nanoparticles missing mitochondrial targeting unit at a low laser power density. Guided by NIR fluorescence imaging and magnetic resonance imaging, then these results are confirmed in a humanized orthotropic lung cancer model. The composite nanoparticles demonstrate high tumor accumulation and excellent tumor regression with minimal side effect upon NIR laser exposure. Therefore, the mitochondria‐targeting composite nanoparticles are expected to be an effective phototherapeutic platform in oncotherapy.     

Poly(N‐phenylglycine)‐Based Nanoparticles as Highly Effective and Targeted Near‐Infrared Photothermal Therapy/Photodynamic Therapeutic Agents for Malignant Melanoma

Malignant melanoma is a highly aggressive tumor resistant to chemotherapy. Therefore, the development of new highly effective therapeutic agents for the treatment of malignant melanoma is highly desirable. In this study, a new class of polymeric photothermal agents based on poly(N‐phenylglycine) (PNPG) suitable for use in near‐infrared (NIR) phototherapy of malignant melanoma is designed and developed. PNPG is obtained via polymerization of N‐phenylglycine (NPG). Carboxylate functionality of NPG allows building multifunctional systems using covalent bonding. This approach avoids complicated issues typically associated with preparation of polymeric photothermal agents. Moreover, PNPG skeleton exhibits pH‐responsive NIR absorption and an ability to generate reactive oxygen species, which makes its derivatives attractive photothermal therapy (PTT)/photodynamic therapy (PDT) dual‐modal agents with pH‐responsive features. PNPG is modified using hyaluronic acid (HA) and polyethylene glycol diamine (PEG‐diamine) acting as the coupling agent. The resultant HA‐modified PNPG (PNPG‐PEG‐HA) shows negligible cytotoxicity and effectively targets CD44‐overexpressing cancer cells. Furthermore, the results of in vitro and in vivo experiments reveal that PNPG‐PEG‐HA selectively kills B16 cells and suppresses malignant melanoma tumor growth upon exposure to NIR light (808 nm), indicating that PNPG‐PEG‐HA can serve as a very promising nanoplatform for targeted dual‐modality PTT/PDT of melanoma.     

MRI‐Visualized,Dual‐Targeting,Combined Tumor Therapy Using Magnetic Graphene‐Based Mesoporous Silica

Targeting peptide‐modified magnetic graphene‐based mesoporous silica (MGMSPI) are synthesized, characterized, and developed as a multifunctional theranostic platform. This system exhibits many merits, such as biocompatibility, high near‐infrared photothermal heating, facile magnetic separation, large T2 relaxation rates (r2), and a high doxorubicin (DOX) loading capacity. In vitro and in vivo results demonstrate that DOX‐loaded MGMSPI (MGMSPID) can integrate magnetic resonance imaging, dual‐targeting recognition (magnetic targeting and receptor‐mediated active targeting), and chemo‐photothermal therapy into a single system for a visualized‐synergistic therapy of glioma. In addition, it is observed that the MGMSPID system has heat‐stimulated, pH‐responsive, sustained release properties. All of these characteristics would provide a robust multifunctional theranostic platform for visualized glioma therapy.     

Light‐Responsive Biodegradable Nanorattles for Cancer Theranostics

Cancer nanotheranostics, integrating both diagnostic and therapeutic functions into nanoscale agents, are advanced solutions for cancer management. Herein, a light‐responsive biodegradable nanorattle‐based perfluoropentane‐(PFP)‐filled mesoporous‐silica‐film‐coated gold nanorod (GNR@SiO₂‐PFP) is strategically designed and prepared for enhanced ultrasound (US)/photoacoustic (PA) dual‐modality imaging guided photothermal therapy of melanoma. The as‐prepared nanorattles are composed of a thin mesoporous silica film as the shell, which endows the nanoplatform with flexible morphology and excellent biodegradability, as well as large cavity for PFP filling. Upon 808 nm laser irradiation, the loaded PFP will undergo a liquid–gas phase transition due to the heat generation from GNRs, thus generating nanobubbles followed by the coalescence into microbubbles. The conversion of nanobubbles to microbubbles can improve the intratumoral permeation and retention in nonmicrovascular tissue, as well as enhance the tumor‐targeted US imaging signals. This nanotheranostic platform exhibits excellent biocompatibility and biodegradability, distinct gas bubbling phenomenon, good US/PA imaging contrast, and remarkable photothermal efficiency. The results demonstrate that the GNR@SiO₂‐PFP nanorattles hold great potential for cancer nanotheranostics.